CYCLIC AMINE OR SALT COMPOSITE, PEST AND ACARICIDE CONTROL AGENT

专利摘要:
A cyclic amine and acaricide compound The present invention relates to a cyclic amine compound represented by formula (1) (in formula (1), cy1-1 and cy2-2 independently represent a group c6-10 aryl or a heterocyclic group; independently represent a hydrogen atom or an unsubstituted C1-6 alkyl group; independently, R 10, R 11, R 20, and R 21 independently represent a hydrogen group. unsubstituted or substituted C1-6 alkyl, unsubstituted or substituted C1-6 alkoxy group, a halogen atom or the like, m, n, p, and r each represent an integer from 0 to 5 and y represents an oxygen atom or the like) or a salt thereof is a acaricide including the same.
公开号:BR112012020986B1
申请号:R112012020986-8
申请日:2011-02-24
公开日:2018-03-27
发明作者:Hamamoto Isami；Koizumi Keiji；Kawaguchi ' Masahiro；Tanigawa Hisashi；Nakamura Takehiko；Kobayashi Tomomi
申请人:Nippon Soda Co., Ltd；
IPC主号:

专利说明:

(54) Title: CYCLIC AMINE COMPOUND OR SALT OF THE SAME, AGENT FOR PEST AND ACARICIDE CONTROL (51) Int.CI .: C07D 451/06; A01N 43/90; A01P 7/02; A61P 33/10; C07D 491/052 (30) Unionist Priority: 10/04/2010 JP 2010-224844, 21/05/2010 JP 2010-117392, 25/02/2010 JP 2010-039839 (73) Holder (s): NIPPON SODA CO ., LTD (72) Inventor (s): ISAMI HAMAMOTO; KEIJI KOIZUMI; MASAHIRO KAWAGUCHI '; HISASHI TANIGAWA; TAKEHIKO NAKAMURA; TOMOMI KOBAYASHI
1/134
Invention Patent Descriptive Report for CYCLIC AMINE COMPOUND OR SALT OF THE SAME, AGENT FOR PEST AND ACARICIDE CONTROL.
TECHNICAL FIELD [001] The present invention relates to a cyclic amine compound and an acaricide. More specifically, the present invention relates to a cyclic amine compound and an acaricide that has superior acaricidal activity, superior property and safety and can be synthesized advantageously and industrially.
[002] Priority is claimed for Japanese Patent Application No. 2010-039839, filed on February 25, 2010, Japanese Patent Application No. 2010-117392, filed on May 21, 2010, Japanese Patent Application No. 2010-224844, filed on October 4, 2010, the contents of which are incorporated herein by reference.
PREVIOUS TECHNIQUE [003] A compound represented by formula (A), which is structurally relevant to the compound of the present invention, is described in Patent document 1. It is described that the compound is effective as a stimulant of the serotonin acceptor 4. However, a specific synthesis process and the effect of the compound represented by formula (A), where X represents an oxygen atom, Y represents an alkoxy group and q represents 0, is not described.
Chemical formula 1
Y [004] Additionally, a compound represented by formula (B), a salt and an N-oxide of the compound represented by formula (B) and
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2/134 a pest control agent that includes the compound represented by formula (B) as an active agent, are described in Patent Document 2 (in formula (B), R ¹ represents a hydroxy group or the like, m represents 0 or an integer from 1 to 5, R ² represents a halogen atom or the like, k represents 0 or an integer from 1 to 4, R ³ , R ³¹ , R ⁴ , R ⁴¹ , R ⁵ , R ⁵¹ , R ⁶ , R ⁶¹ and R ⁷ independently represent a hydrogen atom or the like, X represents an oxygen atom or the like, n represents 0 or 1).
Chemical formula 2
(B) [005] In addition, an N-pyridyl piperidine compound represented by formula (C) is described in Patent Document 3. It is described that the compound represented by formula (C) has an acaricidal activity against rust mites and mites ( in formula (C), R ¹ represents a halogen atom, a C1-4 haloalkyl group, a cyano group, a nitro group or a C1-4 alkoxycarbonyl group R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ independently represent a hydrogen atom or a C1-4 alkyl group. R ¹⁰ represents a hydrogen atom or the like. R ¹¹ represents a halogen atom or the like. X represents an oxygen atom or a sulfur atom, m represents an integer from 1 to 4. n represents 1 or 2).
Chemical formula 3
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3/134
LITERATURE OF THE PREVIOUS TECHNIQUE
Patent Documents
Patent Document 1: Publication of Patent Application
Unexamined Japanese No. Hei 8-34784
Patent Document 2: WO2005 / 095380
Patent Document 3: WO 2008/026658
DESCRIPTION OF THE INVENTION
Problems to be solved by the invention [006] Traditional mites, although they can be industrially and advantageously synthesized and used safely, several of them lack other properties such as residual effectiveness. In addition, safety requirements such as decreasing the harmful effect of chemicals on plants, decreasing or neutralizing toxicity to humans, livestock or marine life, have increased each year.
[007] Therefore, the aim of the present invention is to provide a new cyclic amine compound and an acaricide, which has superior acaricidal activity, has superior property and safety and can be synthesized advantageously and industrially.
[008] Furthermore, the aim of the present invention is to provide a hydroxylamine compound that is suitable for synthesizing the cyclic amine compound used as an active ingredient in the acaricide.
Means for Solving Problems [009] In order to achieve the above objectives, the present inventors conducted extensive studies. As a result, the present inventors have found that a cyclic amine compound that has a specific structure or a salt thereof can be used as an acaricide that has superior acaricidal activity, excellent properties and a high safety. In addition, the present inventors have discovered that a hydroxylamine compound that has
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4/134 a specific structure or a salt thereof, is suitable for an intermediate to synthesize the cyclic amine compound having a specific structure or salt thereof.
[0010] The present invention was obtained based on that perception.
[0011] In other words, the present invention is as follows:
[1] A cyclic amine compound represented by formula (1) or a salt thereof:
Chemical formula 4
(I) in formula (I),
Cy ¹ and Cy ² independently represent a C610 aryl group or a heterocyclyl group;
in formula (I), R ^1a , R ^1b , R ^2a , R ^2b , R ^3a , R ^3b , R ^4a , R ^4b and R ^5a independently represent a hydrogen atom or an unsubstituted or substituted C1-6 alkyl group;
R ^1a and R ^2a , or R ^3a and R ^4a are linked together to form an unsubstituted or substituted C3-6 alkylene group, an unsubstituted or substituted C3-6 alkenylene group, a group represented by the formula: -CH ₂ OCH ₂ -, a group represented by the formula: CH ₂ SCH ₂ -, a group represented by the formula: -CH ₂ C (= O) CH ₂ - or a group represented by the formula: -CH ₂ NR ⁶ CH ₂ -, (provided that R ⁶ represents a hydrogen atom, an unsubstituted or substituted C1-6 alkyl group, an unsubstituted or substituted C1-7 acyl group or an unsubstituted or substituted C1-6 alkoxycarbonyl group):
in formula (I), R ¹⁰ , R ¹¹ , R ²⁰ and R ²¹ independently represent an unsubstituted or substituted C1-6 alkyl group, an unsubstituted or substituted C3-8 cycloalkyl group, a C2-6 alPetition group 870170092471, from 11/29/2017, p. 7/143
5/134 unsubstituted or substituted kenyl, an unsubstituted or substituted C2-6 alkynyl group, a hydroxy group, an oxo group, an unsubstituted or substituted C1-6 alkoxy group, an unsubstituted or substituted C3-8 cycloalkoxy group, an unsubstituted or substituted C2-6 alkenyloxy group, an unsubstituted or substituted C2-6 alkynyloxy group, a carboxyl group, an unsubstituted or substituted C1-7 acyl group, an unsubstituted or substituted C1-6 alkoxycarbonyl group, a group Unsubstituted or substituted C3-8 cycloalkyloxycarbonyl, unsubstituted or substituted C2-6 alkenyloxycarbonyl group, unsubstituted or substituted C2-6 alkynyloxycarbonyl group, unsubstituted or substituted C6-10 aryloxycarbonyl group, unsubstituted or substituted heterocyclyloxycarbonyl group an unsubstituted or substituted C1-7 acyloxy group, an unsubstituted or substituted C1-6 alkoxycarbonyloxy group, an unsubstituted C3-8 cycloalkyloxycarbonyloxy group substituted or substituted, an unsubstituted or substituted C2-6 alkenyloxycarbonyloxy group, an unsubstituted or substituted C2-6 alkynyloxycarbonyloxy group, an unsubstituted or substituted C1-6 alkyl aminocarbonyloxy group, an unsubstituted or substituted C3-8 cycloalkyl aminocarbonyloxy group an unsubstituted or substituted C2-6 alkenyl aminocarbonyloxy group, an unsubstituted or substituted C2-10 alkynyl aminocarbonyloxy group, an unsubstituted or substituted C6-10 aryl aminocarbonyloxy group, an unsubstituted or substituted heterocyclyl aminocarbonyloxy group, an unsubstituted aminooxy group or substituted, an unsubstituted or substituted C1-6 alkylidene aminooxy group, an unsubstituted or substituted C6-10 aryl group, an unsubstituted or substituted heterocyclyl group, an unsubstituted or substituted C6-10 aryloxy group, an unsubstituted heterocyclyloxy group or substituted, a substituted sulfonyloxy group, an amino group, a C1-6 alkyl amino group unsubstituted or substituted, an unsubstituted or substituted C3-8 cycloalkyl amino group 870170092471, of 11/29/2017, p. 8/143
6/134 substituted, an unsubstituted or substituted C2-6 alkenyl amino group, an unsubstituted or substituted C2-6 alkynyl amino group, an unsubstituted or substituted C6-10 aryl amino group, an unsubstituted or substituted amino heterocyclyl group, an unsubstituted or substituted hydroxylamino group, an unsubstituted or substituted C1-7 acyl amino group, an unsubstituted or substituted C1-6 alkoxycarbonyl group, an unsubstituted or substituted C2-6 alkenyloxycarbonyl group, a C2-6 alkynyloxycarbonyl group unsubstituted or substituted amino, C6-10 aryloxycarbonyl amino unsubstituted or substituted, heterocyclyloxycarbonyl amino unsubstituted or substituted, sulfonyl substituted amino group, unsubstituted or substituted aminocarbonyl group, mercapto group, C1-6 group unsubstituted or substituted alkylthio, an unsubstituted or substituted C3-8 cycloalkylthio group, an unsubstituted or substituted C2-6 alkenylthio group an unsubstituted or substituted C2-6 alkynyl thio group, an unsubstituted or substituted C6-10 aryl thio group, an unsubstituted or substituted heterocyclyl thio group, a thiocarbonyl (C1-6 alkyl unsubstituted or substituted) group, a thiocarbonyl (C16 alkoxy unsubstituted or substituted) group, a carbonyl (C1-6 alkyl thio unsubstituted or substituted) group, a thiocarbonyl (C1-6 alkyl thio unsubstituted or substituted) group, a substituted sulfinyl group, a substituted sulfonyl group , a pentafluorsulfanyl group, a C1-6 alkyl trisubstituted silyl group, a C6-10 aryl trisubstituted silyl group, a cyano group, a nitro group or a halogen atom;
R ¹⁰ and R ¹¹ of Cy ¹ can independently form a ring or bond to form a ring or bond with the atoms that make up Cy ¹ to form a ring; R ²⁰ and R ²¹ of Cy ² can independently form a ring or bond to form a ring or bond with the atoms that make up Cy ² to form a ring;
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7/134 in formula (I), m represents the number of R ¹⁰ and represents an integer from 0 to 5, when m is 2 or more, R ¹⁰ s can be the same or different;
in formula (I), n represents the number of R ¹¹ and represents an integer from 0 to 5, when n is 2 or more, R ¹¹ s can be the same or different;
in formula (I), p represents the number of R ²⁰ and represents an integer from 0 to 5, when p is 2 or more, R ²⁰ s can be the same or different;
in formula (I), r represents the number of R ²¹ and represents an integer from 0 to 5, when r is 2 or more, R ²¹ s can be the same or different;
in formula (I), Y represents an oxygen atom or a sulfur atom.
[2] The cyclic amine compound or salt thereof according to [1], in which in formula (I), Cy ¹ represents a phenyl group, a pyrazolyl group, a thiadiazolyl group, a pyridyl group, a pyrimidinyl group or a pyridazinyl group, and Cy ² represents a phenyl group, a pyrazolyl group, a thiadiazolyl group, a pyridyl group, a pyrimidinyl group, or a pyridazinyl group.
[3] The cyclic amine compound or salt thereof according to [1] or [2], wherein in formula (I), R ¹⁰ represents a C1-6 alkyl group, a C1-6 C1-6 alkoxy group alkyl, a C1-6 alkoxy group, C1-6 alkoxy, C1-6 alkyl, a C2-6 alkenyl group, a hydroxy group, a C1-6 alkoxy group, a C1-6 haloalkoxy group, a C3-8 cycloalkoxy group, a C2-6 alkenyloxy group, a C2-6 haloalkenyloxy group, a C2-6 alkynyloxy group, a C2-6 haloalkynoxy group, a C1-6 alkoxy C1-6 alkoxy group, a C3-8 cycloalkyl C1-6 alkoxy group, a cyan group C1-6
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8/134 alkoxy, a C1-7 acyl C1-6 alkoxy group, a C1-6 alkoxy hydroxy group, a C1-7 acyloxy group, a C1-6 alkoxycarbonyl group, a C2-6 alkenyloxycarbonyl group, a C2-6 group alkynyloxycarbonyl, a C16 alkoxycarbonyloxy group, a C1-6 alkyl aminocarbonyloxy group, a C6-10 aryl group, a heterocyclyl group, a C1-6 haloalkyl sulfonyloxy group, a C1-6 alkylidene aminooxy group, a C1-6 alkoxycarbonyl amino group, an amino group unsubstituted or substituted C7-11 aralkyl group, unsubstituted or substituted C711 aralkyloxy group, C1-6 alkylthio group or nitro group;
in formula (I), R ¹¹ represents a cyano group, a halogen atom, a pentafluorsulfanyl group, a C1-6 haloalkyl group, a C2-6 haloalkenyl group or a C2-6 haloalkynyl group;
in formula (I), R ²⁰ represents a cyano group, a halogen atom, a pentafluorsulfanyl group, a C1-6 haloalkyl group, a C2-6 haloalkenyl group or a C2-6 haloalkynyl group; and in formula (I), R ²¹ represents a C1-6 alkyl group, a C1-6 alkoxy C1-6 alkyl group, a C1-6 alkoxy C1-6 alkoxy C1-6 alkyl, a hydroxy group, a C1 group -6 alkoxy, a C1-6 haloalkoxy group, a C2-6 haloalkenyloxy group, a C2-6 haloalkynoxy group, a C1-6 alkoxy C1-6 alkoxy group, a C3-8 cycloalkyl C1-6 alkoxy group, a C1 group -6 alkoxycarbonyl, a C2-6 alkenyloxycarbonyl group, a C2-6 alkynyloxycarbonyl group, a C1-6 alkylidene aminooxy group, a C1-6 alkoxycarbonyl amino group, an unsubstituted or substituted C7-11 aralkyl group, a C7-11 group unsubstituted or substituted aralkyloxy or a nitro group.
[4] The cyclic amine compound or a salt thereof according to any one of [1] to [3], where
Cy ¹ represents a phenyl group;
R ^1b , R ^2b , R ^3a , R ^3b , R ^4a , R ^4b and R ^5a represent a hydrogen atom;
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R ^1a and R ^2a bond to form an unsubstituted or substituted C3-6 alkylene group, an unsubstituted or substituted C3-6 alkenylene group, a group represented by the formula: -CH2OCH2-, a group represented by the formula: -CH2SCH2- , a group represented by the formula: -CH2C (= O) CH2- or a group represented by the formula: -CH2NR ⁶ CH2- (provided that R ⁶ represents a hydrogen atom, an unsubstituted or substituted C1-6 alkyl group, a unsubstituted or substituted C1-7 acyl group or unsubstituted or substituted C1-6 alkoxycarbonyl group);
Cy ² represents a pyridine-2-yl group;
Y represents an oxygen atom; r represents 0; and p represents an integer from 0 to 4.
[5] A cyclic amine compound represented by formula (II) or a salt thereof:
Chemical formula 5
in formula (II), R ¹⁰ , m, R ¹¹ , n and R ²⁰ are the same as previously defined in formula (I), in formula (II), A represents an unsubstituted or substituted C 3-6 alkylene group, a group C3-6 unsubstituted or substituted alkenylene, a group represented by the formula: -CH ₂ OCH ₂ -, a group represented by the formula: -CH ₂ SCH ₂ -, a group represented by the formula: -CH ₂ C (= O) CH ₂ - or a group represented by the formula: -CH ₂ NR ⁶ CH ₂ - (provided that R ⁶ represents a hydrogen atom, an unsubstituted or substituted C1-6 alkyl group, an unsubstituted or substituted C1-7 acyl group or a C1-6 alkoxycarbonyl group does not
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10/134 substituted or substituted), in formula (II), p 'represents the number of R ²⁰ and represents an integer from 0 to 4. When p' is 2 or more, R ²⁰ s are the same or different.
[6] The cyclic amine compound according to [5], wherein in formula (II), R ¹⁰ represents a C1-6 alkyl group, a C1-6 alkoxy group C1-6 alkyl, a C1-6 alkoxy group C1-6 alkoxy C1-6 alkyl, a C2-6 alkenyl group, a hydroxy group, a C1-6 alkoxy group, a C1-6 haloalkoxy group, a C3-8 cycloalkoxy group, a C2-6 alkenyloxy group, a group C2-6 haloalkenyloxy, a C2-6 alkynyloxy group, a C2-6 haloalkynyloxy group, a C1-6 alkoxy group C1-6 alkoxy, a C3-8 cycloalkyl group C1-6 alkoxy, a cyano group C1-6 alkoxy, a group C1-7 acyl C1-6 alkoxy group, a C1-6 alkoxy hydroxy group, a C1-7 acyloxy group, a C1-6 alkoxycarbonyl group, a C2-6 alkenyloxycarbonyl group, a C2-6 alkynyloxycarbonyl group, a C16 alkoxycarbonyloxy group , a C1-6 alkyl aminocarbonyloxy group, a C6-10 aryl group, a heterocyclyl group, a C1-6 haloalkyl sulfonyloxy group, a C1-6 alkylidene aminooxy group, a C1-6 alkoxycarbonyl amino group, a C7-11 aralkyl group not replaced or replaced o, an unsubstituted or substituted C7-11 aralkyloxy group, a C1-6 alkylthio group or a nitro group;
in formula (II), R ¹¹ represents a cyano group, a halogen atom, a pentafluorsulfanyl group, a C1-6 haloalkyl group, a C2-6 haloalkenyl group or a C2-6 haloalkynyl group; and in formula (II), R ²⁰ represents a cyano group, a halogen atom, a pentafluorsulfanyl group, a C1-6 haloalkyl group, a C2-6 haloalkenyl group or a C2-6 haloalkynyl group.
[7] A pest control agent that comprises at least one selected from a cyclic amine compound or salt thereof according to any one of [1] to [6] as an ingrePetição 870170092471, 29/11/2017 , p. 13/143
11/134 active customer.
[8] An acaricide comprising at least one selected from a cyclic amine compound or salt thereof according to any one of [1] to [6] as an active ingredient.
[9] A hydroxylamine compound represented by formula (III) or a salt thereof:
Chemical formula 6 / ^Cyí V (R) _n ^R
(ΠΓ)
RR “in formula (III), Cy ¹ represents C6-10 aryl group or a heterocyclyl group;
in formula (III), R ^1a , R ^1b , R ^2a , R ^2b , R ^3a , R ^3b , R ^4a , R ^4b and R ^5a independently represent a hydrogen atom or a group>2a> 3a po C1-6 alkyl not replaced or replaced; and R ^1a and R ^za , or R ^ja and R ^4a linked together to form an unsubstituted or substituted C3-6 alkylene group, an unsubstituted or substituted C3-6 alkenylene group, a group represented by the formula: -CH2OCH2-, a group represented by the formula: -CH2SCH2-, a group represented by the formula: -CH2C (= O) CH2- or a group represented by the formula: CH2NR ⁶ CH2- (provided that R ⁶ represents a hydrogen atom, a C1-6 group unsubstituted or substituted alkyl, an unsubstituted or substituted C1-7 acyl group or an unsubstituted or substituted C1-6 alkoxycarbonyl group);
in formula (III), R ¹⁰ and R ¹¹ independently represent an unsubstituted or substituted C1-6 alkyl group, an unsubstituted or substituted C3-8 cycloalkyl group, an unsubstituted or substituted C2-6 alkenyl group, a C2- 6 unsubstituted or substituted alkynyl, a hydroxy group, an oxo group, a C1-6 alkoxy group
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12/134 unsubstituted or substituted, an unsubstituted or substituted C3-8 cycloalkoxy group, an unsubstituted or substituted C2-6 alkenyloxy group, an unsubstituted or substituted C2-6 alkynyloxy group, a carboxyl group, a C1-7 group unsubstituted or substituted acyl, an unsubstituted or substituted C1-6 alkoxycarbonyl group, an unsubstituted or substituted C3-8 cycloalkyloxycarbonyl group, an unsubstituted or substituted C2-6 alkenyloxycarbonyl group, an unsubstituted or substituted C26 alkynyloxycarbonyl group, a group C6-10 unsubstituted or substituted aryloxycarbonyl, an unsubstituted or substituted heterocyclyloxycarbonyl group, an unsubstituted or substituted C1-7 acyloxy group, an unsubstituted or substituted C1-6 alkoxycarbonyloxy group, an unsubstituted or substituted C3-8 cycloalkyloxycarbonyloxy group, an unsubstituted or substituted C2-6 alkenyloxycarbonyloxy group, an unsubstituted or substituted C2-6 alkynyloxycarbonyloxy group substituted or substituted C1-6 alkyl aminocarbonyloxy group, unsubstituted or substituted C3-8 cycloalkyl aminocarbonyloxy group, unsubstituted or substituted C2-6 alkenyl aminocarbonyloxy group, unsubstituted or substituted C2-6 alkynyl aminocarbonyloxy group an unsubstituted or substituted C6-10 aryl aminocarbonyloxy group, an unsubstituted or substituted heterocyclyl aminocarbonyloxy group, an unsubstituted or substituted aminooxy group, an unsubstituted or substituted C1-6 alkylidene aminooxy group, an unsubstituted or substituted C6-10 aryl aminooxy group substituted, an unsubstituted or substituted heterocyclyl group, an unsubstituted or substituted C6-10 aryloxy group, an unsubstituted or substituted heterocyclyloxy group, a sulfonyloxy group, an amino group, an unsubstituted or substituted C1-6 alkyl amino group, one group C3-8 cycloalkyl amino unsubstituted or substituted 870170092471, of 11/29/2017, p. 15/143
13/134, an unsubstituted or substituted C2-6 alkenyl amino group, an unsubstituted or substituted C2-6 alkynyl amino group, an unsubstituted or substituted C6-10 aryl amino group, an unsubstituted or substituted amino heterocyclyl group, an unsubstituted or substituted hydroxylamino group, an unsubstituted or substituted C1-7 acyl amino group, an unsubstituted or substituted C1-6 alkoxycarbonyl group, an unsubstituted or substituted C2-6 alkenyloxycarbonyl group, a C2-6 alkynyloxycarbonyl group unsubstituted or substituted amino, C6-10 aryloxycarbonyl amino unsubstituted or substituted, heterocyclyloxycarbonyl amino unsubstituted or substituted, sulfonyl substituted amino group, unsubstituted or substituted aminocarbonyl group, mercapto group, C1-6 group unsubstituted or substituted alkylthio, an unsubstituted or substituted C3-8 cycloalkylthio group, an unsubstituted or substituted C2-6 alkenylthio group substituted or substituted C2-6 alkynyl thio group, an unsubstituted or substituted C6-10 aryl thio group, an unsubstituted or substituted heterocyclyl thio group, a thiocarbonyl (C1-6 alkyl unsubstituted or substituted) group, a thiocarbonyl (C16 alkoxy unsubstituted or substituted) group, a carbonyl (C1-6 alkyl thio unsubstituted or substituted) group, a thiocarbonyl (C1-6 alkyl thio unsubstituted or substituted) group, a substituted sulfinyl group, a substituted sulfonyl group , a pentafluorsulfanyl group, a C1-6 alkyl trisubstituted silyl group, a C6-10 aryl trisubstituted silyl group, a cyano group, a nitro group or a halogen atom;
R ¹⁰ and R ¹¹ of Cy ¹ can independently form a ring or be linked to form a ring or bond with the atoms that constitute Cy ¹ to form a ring;
in formula (III), m represents the number of R ¹⁰ and represents an integer from 0 to 5, when m is 2 or more, R ¹⁰ s can be
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14/134 the same or different;
in formula (III), n represents the number of R ¹¹ and represents an integer from 0 to 5, when n is 2 or more, R ¹¹ s can be the same or different.
[10] The hydroxylamine compound or salt thereof according to [9], in which in formula (III), Cy ¹ represents a phenyl group, a pyrazolyl group, a thiadiazolyl group, a pyridyl group, a pyrimidinyl group or pyridazinyl group.
[11] The hydroxylamine compound or salt thereof according to [9] or [10], wherein in formula (III), R ¹⁰ represents a C1-6 alkyl group, a C1-6 alkoxy C1-6 alkyl group , a C1-6 alkoxy group C1-6 alkoxy C1-6 alkyl group, a C2-6 alkenyl group, a hydroxy group, a C1-6 alkoxy group, a C1-6 haloalkoxy group, a C3-8 cycloalkoxy group, a group C2-6 alkenyloxy, a C2-6 haloalkenyloxy group, a C2-6 alkynyloxy group, a C2-6 haloalkynoxy group, a C1-6 alkoxy C1-6 alkoxy group, a C3-8 cycloalkyl C1-6 alkoxy group, a group cyano C1-6 alkoxy, a C1-7 acyl C1-6 alkoxy group, a C1-6 alkoxy hydroxy group, a C1-7 acyloxy group, a C1-6 alkoxycarbonyl group, a C2-6 alkenyloxycarbonyl group, a C2- 6 alkynyloxycarbonyl, a C16 alkoxycarbonyloxy group, a C1-6 alkyl aminocarbonyloxy group, a C6-10 aryl group, a heterocyclyl group, a C1-6 haloalkyl sulfonyloxy group, a C1-6 alkylidene aminooxy group, a C1-6 alkoxycarbonyl amino group , a C7-11 aralkyl group did not substituted or substituted, an unsubstituted or substituted C7-11 aralkyloxy group, a C1-6 alkylthio group or a nitro group; and in formula (III), R ¹¹ represents a cyano group, a halogen atom, a pentafluorsulfanyl group, a C1-6 haloalkyl group, a C2-6 haloalkenyl group or a C2-6 haloalkynyl group.
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Effects of the Invention [0012] The cyclic amine compound or salt thereof according to the present invention makes it possible to effectively prevent the mites that are harmful to agricultural crops or harmful in terms of hygiene.
[0013] The hydroxylamine compound or salt thereof according to the present invention makes it possible to easily synthesize the cyclic amine compound or salt thereof according to the present invention.
BEST MODE FOR CARRYING OUT THE INVENTION Cyclic amine compound [0014] The amine compound of the present invention is represented by formula (I) or (II). In addition, the salt of the cyclic amine compound of the present invention is a salt of a cyclic compound represented by formula (I) or (II).
[0015] The expression “unsubstituted” in this description means that a base group is the only group that constitutes the group. In addition, unless specifically stated otherwise, a group has the meaning of being "unsubstituted" when the group is not described as being "substituted" and described using the name of the base group.
[0016] On the other hand, the term "substituted" means that any of the hydrogen atoms in the base group are replaced by a group that is the same or different from the base group. The "substituted" group can be replaced by one substituent or two or more substituents. The two or more substituents can be the same or different.
[0017] The expression "C1-6", for example, means that the base group has 1 to 6 carbon atoms. This number does not include the number of carbon atoms that make up the substituents. For example, a
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16/134 butyl group substituted by an ethoxy group is classified into a C2 alkoxy C4 alkyl group.
[0018] The "substituent" is not particularly limited as long as it is chemically permissible and achieves the effects of the present invention.
[0019] Examples of "substituent" include a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom, an iodine atom and the like; a C1-6 alkyl group such as a methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, s-butyl group, i-butyl group, t-butyl group, n-pentyl group, n group -hexyl or the like; a C3-8 cycloalkyl group such as a cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloeptyl group or the like; a C2-6 alkenyl group such as a vinyl group, 1-propenyl group, 2-propenyl group, 1butenyl group, 2-butenyl group, 3-butenyl group, 1-methyl-2-propenyl group, 2-methyl-2 group -propenyl, group 1-pentenyl, group 2-pentenyl, group
3- pentenyl, group 4-pentenyl, group 1-methyl-2-butenyl, group 2-methyl-2butenyl, group 1-hexenyl, group 2-hexenyl, group 3-hexenyl, group
4-hexenyl, 5-hexenyl group, or the like; a C3-8 cycloalkenyl group such as a 2-cyclopropenyl group, 2-cyclopentenyl group, 3-cyclohexenyl group, 4-cyclooctenyl group or the like; C26 alkynyl group such as an ethynyl group, 1-propynyl group, 2propynyl group, 1-butynyl group, 2-butynyl group, 3-butynyl group, 1methyl-2-propynyl group, 2-methyl-3-butynyl group, group 1 -pentinyl, 2pentinyl group, 3-pentynyl group, 4-pentinyl group, 1-methyl-2-butynyl group, 2-methyl-3-pentinyl group, 1-hexynyl group, 1,1-dimethyl-2-butynyl group or similar;
a C1-6 alkoxy group such as a methoxy group, ethoxy group, n-propoxy group, i-propoxy group, n-butoxy group, s-butoxy group, i-butoxy group, t-butoxy group or the like; a group C2-6 alkeniPetition 870170092471, of 11/29/2017, p. 19/143
17/134 loxy such as a vinyloxy group, allyoxy group, propenyloxy group, butenyloxy group or the like; a C2-6 alkynyloxy group such as an ethynyloxy group, propargyloxy group or the like; a C6-10 aryl group such as a phenyl group, naphthyl group or the like; a C610 aryloxy group such as a phenoxy group, 1-naphthoxy group or the like; a C7-11 aralkyl group such as a benzyl group, phenethyl group or the like; a C7-11 aralkyloxy group such as a benzyloxy group, phenethyloxy group or the like; a C1-7 acyl group such as a formyl group, acetyl group, propionyl group, benzoyl group, cyclohexyl carbonyl group or the like; a C1-7 acyloxy group such as a formyloxy group, acetyloxy group, propionyloxy group, benzoyloxy group, cyclohexyl carbonyloxy group or the like; a C1-6 alkoxycarbonyl group such as a methoxycarbonyl group, ethoxycarbonyl group, n-propoxycarbonyl group, i-propoxycarbonyl group, n-butoxycarbonyl group, t-butoxycarbonyl group or the like; a carboxyl group;
a hydroxy group; an oxo group; a C1-6 haloalkyl group such as a chloromethyl group, chloroethyl group, trifluoromethyl group, 1,2-dichloro-n-propyl group, 1-fluoro-n-butyl group, perfluoro-npentyl group or the like; a C2-6 haloalkenyl group such as a 2-chloro-1-propenyl group, 2-fluoro-1-butenyl group or the like; a C2-6 haloalkynyl group such as a 4,4-dichloro-1-butynyl group, 4-fluoro-1-pentynyl group, 5-bromo-2-pentynyl group or the like; a C1-6 haloalkoxy group such as a 2-chloro-n-propoxy group, 2,3dichlorobutoxy group or the like; a C2-6 haloalkenyloxy group such as a 2-chloropropenyloxy group, 3-bromobutenyloxy group or the like; a C6-10 haloaryl group such as a 4-chlorophenyl group, 4-fluorophenyl group, 2,4-dichlorophenyl group or the like; a C6-10 haloaryloxy group such as a 4-fluorophenyloxy group, 4-chloro-1-naphthoxy group or the like; a C1-7 acyl group substituted with halogen such as a chloroacetyl group, trifluoracetyl group, trichloroacetyl group,
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18/134
4-chlorobenzoyl or the like;
a cyan group; an isocyan group; a nitro group; an isocyanate group; a cyanate group; an amino group; a C1-6 alkyl amino group such as a methyl amino group, dimethyl amino group, diethyl amino group or the like; a C6-10 aryl amino group such as an aniline group, amino naphthyl group or the like; a C7-11 aralkyl amino group such as a benzyl amino group, phenylethyl amino group or the like; a C1-7 acyl amino group such as a formyl amino group, acetyl amino group, propanoyl amino group, butyryl amino group, i-propyl carbonyl amino group, benzoyl amino group or the like; a C1-6 alkoxycarbonyl amino group such as a methoxycarbonyl amino group, ethoxycarbonyl amino group, n-propoxycarbonyl amino group, i-propoxycarbonyl amino group, or the like; an unsubstituted or substituted aminocarbonyl group such as an aminocarbonyl group, dimethyl aminocarbonyl group, phenyl aminocarbonyl group, N-phenyl-Nmethyl aminocarbonyl group or the like; an imino-substituted C1-6 alkyl group such as an iminomethyl group, (1-imino) ethyl group, (1-imino) -n-propyl group or the like; a C 1-6 alkyl group substituted with hydroxyimino such as a hydroxyiminomethyl group, (1hydroxyimino) ethyl group, (1-hydroxyimino) propyl group, methoxyiminomethyl group, (1-methoxyimino) ethyl group or the like;
a mercapto group; an isothiocyanate group; a thiocyanate group; a C1-6 alkyl thio group such as a methyl thio group, ethyl thio group, n-propyl thio group, i-propyl thio group, n-butyl thio group, i-butyl thio group, s-butyl thio group, t group butyl uncle or the like; a C2-6 alkenyl thio group such as a vinyl thio group, allyl thio group or the like; a C2-6 alkynyl thio group such as an ethynyl thio group, propargyl thio group or the like;
a C6-10 aryl thio group such as a phenyl thio group, thio naphthyl group or the like; a heterocyclyl group such as a group
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19/134 thiazolyl thio, pyridyl thio group or the like; a C7-11 aralkyl thio group such as a benzyl thio group, phenethyl thio group or the like; a (C1-6 alkyl thio) carbonyl group such as a (methyl thio) carbonyl group, a (ethyl thio) carbonyl group, a (n-propyl thio) carbonyl group, a (ipropyl thio) carbonyl group, a (n- butyl thio) carbonyl, (i-butyl thio) carbonyl group, (s-butyl thio) carbonyl group, (t-butyl thio) carbonyl group or the like;
a C1-6 alkyl sulfinyl group such as a methyl sulfinyl group, ethyl sulfinyl group, t-butyl sulfinyl group or the like; a C2-6 alkenyl sulfinyl group such as an n-allyl sulfinyl group or the like;
a C2-6 alkynyl sulfinyl group such as a propargyl sulfinyl group or the like; a C6-10 aryl sulfinyl group such as a phenyl sulfinyl group or the like; a heterocyclyl sulfinyl group such as a thiazolyl sulfinyl group, pyridyl sulfinyl group or the like; a C7-11 aralkyl sulfinyl group such as a benzyl sulfinyl group, phenethyl sulfinyl group or the like; a C1-6 alkyl sulfonyl group such as a methyl sulfonyl group, ethyl sulfonyl group, t-butyl sulfonyl group or the like; a C2-6 alkenyl sulfonyl group such as an allyl sulfonyl group or the like; a C2-6 alkynyl sulfonyl group such as a propargyl sulfonyl group or the like; a C6-10 aryl sulfonyl group such as a phenyl sulfonyl group or the like; a heterocyclyl sulfonyl group such as a thiazolyl sulfonyl group, pyridyl sulfonyl group or the like; a C7-11 aralkyl sulfonyl group such as a benzyl sulfonyl group, phenethyl sulfonyl group or the like;
a 5-membered heteroaryl such as a pyrrolyl group, furyl group, thienyl group, imidazolyl group, pyrazolyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, triazolyl group, oxadiazolyl group, thiadiazolyl group, or the like; a 6-membered heteroaryl group as well as a group
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Pyridyl, pyrazinyl group, pyrimidinyl group, pyridazinyl group, triazinyl group or the like; a saturated heterocyclyl group such as an aziridinyl group, epoxy group, pyrrolidinyl group, tetrahydrofuranyl group, piperidyl group, piperazinyl group, morpholinyl group or the like; a C1-6 alkyl trisubstituted silyl group such as a trimethyl silyl group, triethyl silyl group, t-butyl dimethyl silyl group or the like; a triphenyl silyl group or the like; or the like.
[0020] Additionally, these "substituents" can be replaced by other "substituents".
[Cy ¹ , Cy ² ] [0021] In formula (I), Cy ¹ and Cy ² independently represent a C6-10 aryl group or a heterocyclic group.
[0022] The "C6-10 aryl" group of Cy ¹ and Cy ² can be a monocyclic or polycyclic C6-10 aryl group. In the polycyclic aryl group, as long as it includes at least one aromatic ring, the other rings can be a saturated alicyclic ring, an unsaturated alicyclic ring or an aromatic ring. Examples of the C6-10 aryl group include a phenyl group, a naphthyl group, a azulenyl group, an indenyl group, an indanyl group, a tetralinyl group or the like. Among these groups, a phenyl group is preferable as the "C6-10 aryl group" of Cy ¹ or Cy ² . [0023] The "heterocyclyl group" of Cy ¹ and Cy ² is a group in which 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom are included as the atoms that make up the ring. The heterocyclyl group can be a mono-heterocyclyl group or a poly-heterocyclyl group.
[0024] Examples of heterocyclyl group include a 5-membered heteroaryl group, a 6-membered heteroaryl group, a condensed heteroaryl group, a saturated heterocyclyl group, a partially unsaturated heterocyclyl group or the like.
[0025] Examples of a 5-membered heteroaryl group include a
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Pyrrolyl group such as a pyrrol-1-yl group, pyrrol-2-yl group, pyrrol-3-yl group or the like; a furyl group such as a furan-2-yl group, furan-3-yl group or the like; a thienyl group such as a thiophen-2-yl group, thiophen-3-yl group or the like; an imidazolyl group such as an imidazol-1-yl group, imidazol-2-yl group, imidazol-4-yl group, imidazol-5-yl group or the like; a pyrazolyl group such as a pyrazol-1-yl group, pyrazol-3-yl group, pyrazol-4-yl group, pyrazol-5-yl group or the like; an oxazolyl group such as an oxazol-2-yl group, oxazol-4-yl group, oxazol-5-yl group or the like; an isoxazolyl group such as an isoxazol-3-yl group, isoxazol-4-yl group, isoxazol-5-yl group or the like; a thiazolyl group such as a thiazol-2yl group, thiazol-4-yl group, thiazol-5-yl group or the like; an isothiazolyl group such as an isothiazol-3-yl group, isothiazol-4-yl group, isothiazol-5-yl group or the like; a triazolyl group such as a 1,2,3-triazol-1-yl group, 1,2,3-triazol-4-yl group, 1,2,3-triazol-5-yl group, 1,2,4-triazole-1 group -yl, 1,2,4-triazol-3-yl group, 1,2,4-triazol-5-yl group or the like; an oxadiazolyl group such as a 1,2,4-oxadiazol-3-yl group, 1,2,4-oxadiazol-5-yl group, 1,3,4-oxadiazol-2-yl group or the like; a thiadiazolyl group such as a 1,2,4-thiadiazol-3-yl group, 1,2,4 thiadiazol-5-yl group, 1,3,4-thiadiazol-2-yl group or the like; a tetrazolyl group such as a tetrazol-1-yl group, tetrazol-2-yl group or the like; or the like.
Examples of a 6-membered heteroaryl group include a pyridyl group such as a pyridin-2-yl group, pyridin-3-yl group, pyridin-4-yl group or the like; a pyrazinyl group such as a pyrazin-2-yl group, pyrazin-3-yl group or the like; a pyrimidinyl group such as a pyrimidin-2-yl group, pyrimidin-4-yl group, pyrimidin-5-yl group or the like; a pyridazinyl group such as a pyridazin-3-yl group, pyridazin-4-yl group or the like; a triazinyl group or the like; or the like.
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Examples of the condensed heteroaryl group include an indol-1-yl group, an indol-2-yl group, indol-3-yl group, indol-4-yl group, indol-5-yl group, group indol-6-yl, indol-7-yl group; a benzofuran2-yl group, benzofuran-3-yl group, benzofuran-4-yl group, benzofuran-5yl group, benzofuran-6-yl group, benzofuran-7-yl group; a benzothiophen-2-yl group, benzothiophen-3-yl group, benzothiophen-4-yl group, benzothiophen-5yl group, benzothiophen-6-yl group, benzothiophen-7-yl group; a benzimidazol-1-yl group, benzimidazol-2-yl group, benzimidazol-4-yl group, benzimidazol-5-yl group, benzoxazol-2-yl group, benzoxazol-4-yl group, benzoxazol-5-yl group, benzothiazol-2-yl group, benzothiazol-4-yl group, benzothiazol-5-yl group; a quinolin-2-yl group, quinolin-3-yl group, quinolin-4-yl group, quinolin-5-yl group, quinolin-6-yl group, quinolin-7-yl group, quinolin-8-yl group or similar; or the like.
Examples of other heterocyclyl groups include an aziridin-1-yl group, aziridin-2-yl group, epoxy group; a pyrrolidin-1-yl group, pyrrolidin-2-yl group, pyrrolidin-3-yl group, tetrahydrofuran-2-yl group, tetrahydrofuran-3-yl group; a [1,3] dioxiran-2-yl group, [1,3] dioxiran-4-yl group; a piperidin-1-yl group, piperidin-2-yl group, piperidin-3-yl group, piperidin-4-yl group, piperazin-1-yl group, piperazin-2-yl group, morfolin2-yl group, morfolin group -3-yl, morpholin-4-yl group; to 1,3-benzodioxol-4-yl, 1,3-benzodioxol-5-yl group, 1,4-benzodioxan-5-yl group, 1,4benzodioxan-6-yl group, 3,4-dihydro-2H group -1,5-benzodioxepin-6-yl, group
3,4-dihydro-2H-1,5-benzodioxepin-7-yl, 2,3-dihydrobenzofuran-4-yl group, 2,3-dihydrobenzofuran-5-yl group, 2,3-dihydrobenzofuran-6-yl group group
2,3-dihydrobenzofuran-7-yl; or the like.
[0029] Among these groups, the heterocyclyl group of Cy ¹ or Cy ² is preferably a 5-membered heteroaryl group or a 6-membered heteroaryl group, more preferably a pyrazolyl group, a thiadiazolyl group, a pyridyl group, a pyrimidinyl group or a pyridazinyl group.
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23/134 [0030] In the cyclic amine compound of the present invention, Cy ¹ is preferably a phenyl group and Cy ² is preferably a pyridyl group.
[R ^1a , R ^1b , R ^2a , R ^2b , R ^3a , R ^3b , R ^4a , R ^4b and R ^5a ]
4b
5a [0031] In formula (I), R ^1a , R ^1b , R ^2a , R ^2b , R ^3a , R ^3b , R ^4a , R ^4b and R (hereinafter may be referred to as R ^1a or similar ”) represent independently a hydrogen atom or an unsubstituted or substituted C1-6 alkyl group; R ^1a and R ^2a , or R ^3a and R ^4a bond to form an unsubstituted or substituted C3-6 alkylene group, an unsubstituted or substituted C3-6 alkenylene group, a group represented by the formula: -CH2OCH2-, a group represented by the formula: -CH2SCH2-, a group represented by the formula: CH2C (= O) CH2-, or a group represented by the formula: -CH2NR ⁶ CH2 (provided that R ⁶ represents a hydrogen atom, a C1-6 alkyl group unsubstituted or substituted, an unsubstituted or substituted C1-7 acyl group or an unsubstituted or substituted C1-6 alkoxycarbonyl group). In addition, the group formed by the bonding of R ^1a with R ^2a , R ^3a with R ^4a can be referred to as a "cross-linking portion".
[0032] The "C1-6 alkyl group" of R ^1a or the like may be a linear alkyl group or a branched alkyl group. Examples of an alkyl group include a methyl group, ethyl group, n-propyl group, nbutyl group, pentyl group, n-hexyl group, i-propyl group, i-butyl group, s-butyl group, t-butyl group, group i -pentyl, neopentyl group, 2-methyl butyl group, 2,2-dimethyl propyl group, i-hexyl group or the like. Examples of " ^1a C1-6 substituted alkyl group" of R ^1a or the like include a C3-8 cycloalkyl C1-6 alkyl group such as a cyclopropyl methyl group, 2-cyclopropyl ethyl group, cyclopentyl methyl group, 2-cyclohexyl group ethyl, ethyl 2-cyclooctyl group or the like; a C1-6 haloalkyl group such as a fluoromethyl group, chloromethyl groupPetition 870170092471, of 11/29/2017, p. 26/143
24/134 la, bromomethyl group, difluoromethyl group, dichloromethyl group, dibromomethyl group, trifluoromethyl group, trichloromethyl group, tribromomethyl group, 2,2,2-tolufluorethyl group, 2,2,2-trichlorethyl group, pentafluorethyl group, group 4- fluorbutyl, 4-chlorobutyl group, 3,3,3trifluorpropyl group, 2,2,2-trifluor-1-trifluormethyl group, perfluorexyl group, perchlorohexyl group, perfluoroctyl group, perchlorooctyl group, 2,4,6-trichlorohexyl group, group hexafluorisopropyl, pentafluorisopropyl group, perfluoromethoxy group or the like;
a C 1-6 alkyl hydroxy group such as a hydroxymethyl group, 2-hydroxyethyl group or the like; a C1-6 alkoxy C1-6 alkyl group such as a methoxymethyl group, ethoxymethyl group, methoxyethyl group, ethoxyethyl group, methoxy-n-propyl group, npropoxymethyl group, i-propoxymethyl group, i-propoxyethyl group, sbutoxymethyl group, t group -butoxyethyl or the like; C1-6 alkoxy C1-6 alkoxy C1-6 alkyl such as a methoxymethoxymethyl group, 1methoxyethoxymethyl group, 2-methoxyethoxymethyl group, 2- (1methoxyethoxy) ethyl group, ethyl group 2- (2-methoxyethoxy) or the like; a C 1-6 alkoxy C 1-6 alkyl such as a dimethoxymethyl group, diethoxymethyl group, 2,2-dimethoxyethyl group, 1,2-dimethoxyethyl group, 3,3-dimethoxy n-propyl group, 2,2-diethoxyethyl group or the like; C1-7 acyloxy C1-6 alkyl such as a formyloxymethyl group, acetoxymethyl group, 2-acetoxyethyl group, propionyloxymethyl group, propionyloxyethyl group or the like; an imino-substituted C1-6 alkyl group such as an iminomethyl group, (1-imino) ethyl group, (1imino) propyl group or the like;
a C 1-6 alkyl group substituted by hydroxyimino such as a hydroxyminomethyl group, (1-hydroxyimino) ethyl group, (1hydroxyimino) -n-propyl group, methoxymethylmethyl group, ethyl (1methoxyimino) group or the like;
an unsubstituted or substituted C7-11 aralkyl group as
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25/134 as an unsubstituted or substituted benzyl group, an unsubstituted or substituted phenethyl group or the like; or the like. [0034] Examples of "C3-6 alkylene group" formed by the bonding of R ^1a with R ^2a , or R ^3a with R ^4a include a trimethylene group, a tetramethylene group, a propylene group or the like. Among these groups, a C3-4 alkylene group is preferable.
[0035] Additionally, examples of "C3-6 alkenylene group" include a propenylene group, a 2-butenylene group or the like. Among these groups, a C3-4 alkenylene group is preferable.
[0036] Examples of possible "substituents" include a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom, an iodine atom or the like; a C1-6 alkyl group such as a methyl group, ethyl group, n-propyl group, ipropyl group, n-butyl group, s-butyl group, i-butyl group, t-butyl group, n-pentyl group, n group -hexyl or the like; a C3-6 cycloalkyl group such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group or the like; a C1-6 alkoxy group such as a methoxy group, ethoxy group, n-propoxy group, ipropoxy group, n-butoxy group, s-butoxy group, i-butoxy group, t-butoxy group or the like; a hydroxy group; a C1-6 haloalkyl group such as a chloromethyl group, a chloroethyl group, a trifluoromethyl group, a 1,2-dichloro-n-propyl group, a 1-fluorine-n-butyl group, a perfluoro-n-pentyl group or similar; or the like.
[0037] In the formula -CH ₂ NR ⁶ CH ₂ -, R ⁶ represents a hydrogen atom, an unsubstituted or substituted C1-6 alkyl group, an unsubstituted or substituted C1-7 acyl group or a C1-6 alkoxycarbonyl group not replaced or replaced.
[0038] Examples of "unsubstituted or substituted C1-6 alkyl group" of R ⁶ are the same as those listed as examples of R ^1a or similar.
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26/134 [0039] Examples of R ⁶ "C1-7 acyl group" include a formyl group, an acetyl group, a propionyl group, benzoyl group, cyclohexyl carbonyl group or the like. Examples of R ⁶ "C1-7 substituted acyl group" include a chloroacetyl group, trifluoracetyl group, trichloroacetyl group, 4-chlorobenzoyl group or the like.
Examples of "C1-6 alkoxycarbonyl group" of R ⁶ include a methoxycarbonyl group, ethoxycarbonyl group, npropoxycarbonyl group, i-propoxycarbonyl group, n-butoxycarbonyl group, t-butoxycarbonyl group or the like.
[0041] Examples of "substituted C1-6 alkoxycarbonyl group" of R ⁶ include a C1-6 cycloalkyl C1-6 alkoxycarbonyl group such as a methoxycarbonyl cyclopropyl group, methoxycarbonyl cyclobutyl group, methoxycarbonyl cyclopentyl group, methoxycarbonyl cyclopentyl group, 2-methyl group cyclopropyl methoxycarbonyl, 2,3-dimethyl cyclopropyl methoxycarbonyl group, 2-chlorocyclopropyl methoxycarbonyl group, 2cyclopropyl ethoxycarbonyl group or the like; a C1-6 haloalkoxycarbonyl group such as a fluoromethoxycarbonyl group, chloromethoxycarbonyl group, bromomethoxycarbonyl group, difluormethoxycarbonyl group, dichloromethoxycarbonyl group, dibromomethoxycarbonyl group, trifluoroethoxycarbonyl group, trichloromethoxycarbonyl group, 2,2-trichloromethoxycarbonyl group, tribromethoxycarbonyl group, 2,2-methoxycarbonyl group, 2,2-trichloromethoxycarbonyl group. 2trichloroethoxycarbonyl, pentafluoroethoxycarbonyl group, 4fluorbutoxycarbonyl group, 3,3,3-trifluorpropoxycarbonyl group, 2,2,2trifluoro-1-trifluoromethyl ethoxycarbonyl group, perfluorexyloxycarbonyl group and the like; or the like.
[0042] The following partial structural formulas (a1) - (a4) are shown to specifically explain the crosslinking portion. In formulas (a1) - (a4), * 1 represents the bonding position with Y, * 2 represents the bonding position with the oxygen atom. X's independently represent -CH2-, an oxygen atom, an atom of
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27/134 sulfur, -NR ⁶ -, a carbonyl group or the like. The present invention also includes isomers in which the crosslinking moiety has an exo-relationship or endo-relationship to R ^5a or mixtures thereof.
Chemical formula 7
R R '(a1)
R R *
(a2)

(a3) (a4) [R ¹⁰ , R ¹¹ , R ²⁰ , R ²¹ ] [0043] In formula (I), R ¹⁰ , R ¹¹ , R ²⁰ and R ²¹ (hereinafter referred to as R ¹⁰ or similar) independently represent an unsubstituted or substituted C1-6 alkyl group, an unsubstituted or substituted C3-8 cycloalkyl group, an unsubstituted or substituted C2-6 alkenyl group, an unsubstituted or substituted C2-6 alkynyl group, a hydroxy group, an oxo group, an unsubstituted or substituted C1-6 alkoxy group, an unsubstituted or substituted C3-8 cycloalkoxy group, an unsubstituted or substituted C2-6 alkenyloxy group, an unsubstituted or substituted C2-6 alkynyloxy group, a group carboxyl, an unsubstituted or substituted C1-7 acyl group,
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28/134 an unsubstituted or substituted C1-6 alkoxycarbonyl group, an unsubstituted or substituted C3-8 cycloalkyloxycarbonyl group, an unsubstituted or substituted C2-6 alkenyloxycarbonyl group, an unsubstituted or substituted C2-6 alkynyloxycarbonyl group, a C6 group -10 unsubstituted or substituted aryloxycarbonyl, an unsubstituted or substituted heterocyclyloxycarbonyl group, an unsubstituted or substituted C1-7 acyloxy group, an unsubstituted or substituted C1-6 alkoxycarbonyloxy group, an unsubstituted or substituted C3-8 cycloalkyloxycarbonyloxy group, one unsubstituted or substituted C2-6 alkenyloxycarbonyloxy group, unsubstituted or substituted C2-6 alkynyloxycarbonyloxy group, unsubstituted or substituted C1-6 alkyl aminocarbonyloxy group, unsubstituted or substituted C3-8 cycloalkyl aminocarbonyloxy group, C2-6 group unsubstituted or substituted alkenyl aminocarbonyloxy, an unsubstituted C2-6 alkynyl aminocarbonyloxy group substituted or substituted C6-10 aryl aminocarbonyloxy group, unsubstituted or substituted heterocyclyl aminocarbonyloxy group, unsubstituted or substituted aminooxy group, unsubstituted or substituted C1-6 alkylidene aminooxy group, C6-10 group unsubstituted or substituted aryl, an unsubstituted or substituted heterocyclyl group, an unsubstituted or substituted C6-10 aryloxy group, an unsubstituted or substituted heterocyclyloxy group, a substituted sulfonyloxy group, an amino group, an unsubstituted C1-6 alkyl group substituted or substituted, an unsubstituted or substituted C3-8 cycloalkyl amino group, an unsubstituted or substituted C2-6 alkenyl amino group, an unsubstituted or substituted C2-6 alkynyl amino group, an unsubstituted or substituted C6-10 amino alkenyl group substituted, an unsubstituted or substituted heterocyclyl amino group, an unsubstituted or substituted hydroxylamino group, an unsubstituted C1-7 acyl amino group substituted or substituted, a non-substituted C1-6 alkoxycarbonyl amino groupPetition 870170092471, of 11/29/2017, p. 31/143
29/134 of or substituted, an unsubstituted or substituted C2-6 alkenyloxycarbonyl amino group, an unsubstituted or substituted C2-6 alkynyloxycarbonyl group, an unsubstituted or substituted C6-10 aryloxycarbonyl amino group, an unsubstituted or substituted amino heterocyclylcarbonyl group substituted, a substituted amino sulfonyl group, an unsubstituted or substituted aminocarbonyl group, a mercapto group, an unsubstituted or substituted C1-6 alkylthio group, an unsubstituted or substituted C3-8 cycloalkyl group, an C2-6 alkenyl group unsubstituted or substituted thio, an unsubstituted or substituted C2-6 alkynyl group, an unsubstituted or substituted C6-10 aryl thio group, an unsubstituted or substituted heterocyclyl group, an unsubstituted or substituted C1-6 alkyl group ) thiocarbonyl, a (C 1-6 alkoxy unsubstituted or substituted) thiocarbonyl group, a (C 1-6 alkyl thio unsubstituted or substituted) carbonyl group, a (C 1-6 alkyl thio the unsubstituted or substituted) thiocarbonyl, a substituted sulfinyl group, a substituted sulfonyl group, a pentafluorosulfanyl group, a C1-6 alkyl trisubstituted silyl group, a C6-10 aryl trisubstituted silyl group, a cyano group, a nitro group or a halogen atom.
[0044] R ¹⁰ and R ¹¹ of Cy ¹ can independently form a ring, or linked together to form a ring, or linked with the atoms that constitute Cy ^{1 to} form a ring; R ²⁰ and R ²¹ of Cy ² can independently form a ring, or linked together to form a ring, or linked with the atoms that constitute Cy ^{2 to} form a ring.
[0045] m represents the number of R ¹⁰ and represents an integer from 0 to 5, preferably represents 1. When m is 2 or more, R ¹⁰ can be the same or different.
[0046] n represents the number of R ¹¹ and represents an integer from 0 to 5, preferably represents 1. When n is 2 or more, R ¹¹ can be the same or different.
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30/134 [0047] p represents the number of R ²⁰ and represents an integer from 0 to 5, preferably represents 1. When p is 2 or more, R ²⁰ can be the same or different.
[0048] r represents the number of R ²¹ and represents an integer from 0 to 5, preferably represents 1. When r is 2 or more, R ²¹ can be the same or different.
[0049] Examples of "unsubstituted or substituted C1-6 alkyl group" of R ¹⁰ or similar are the same as those listed as examples of R ^1a or similar.
In addition, unlike examples of R ^1a or similar, examples of "unsubstituted or substituted C1-6 alkyl group" also include a C3-8 cycloalkoxy C1-6 alkyl group such as a chlorocyclohexyloxymethyl group, bromocyclohexyloxymethyl group, 2methyl cyclopropyloxymethyl group, 2,3-dimethyl cyclopropyloxymethyl group, spiro group [2.2] pent-1-yloxymethyl, 1-methyl-spiro group [2.2] pent-1yloxymethyl, 1-hydroxymethyl spiro [2.2] pent-1-yloxymethyl group, group
4,4-diflúor-spiro [2.2] pent-1-yloxymethyl, bicycloprop-2-yl group, oxymethyl group, or the like; a substituted C3-8 cycloalkyl C1-6 alkoxy C1-6 alkoxy group, such as a chlorocyclohexyl methoxymethyl group, bromocyclohex methoxymethyl group, 2-methyl cyclopropyl methoxymethyl group, 2,3-dimethyl cyclopropyl methoxymethyl group, spiro group [2.2] 1-yl methoxymethyl, 1-methyl-spiro group [2.2] pent-1-yl methoxymethyl, 1-hydroxymethyl spiro [2.2] pent-1-yl methoxymethyl, 4,4-difluorespiro group [2.2] pent-1-yl methoxymethyl, bicycloprop-2-yl group, methoxymethyl group, or the like; or the like.
[0051] Examples of R ¹⁰ "C3-8 cycloalkyl group" include a cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloeptyl group or the like.
[0052] Examples of "C3-8 cycloalkyl group" include a chlorocyclohexyl group, bromocyclohexyl group, 2-methyl cyclopropyl group,
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2.3- dimethyl cyclopropyl, spiro group [2.2] pent-1-yl, group 1-methylpiro [2.2] pent-1-yl, group 1-hydroxymethyl spiro [2.2] pent-1-yl, group
4.4- difluoro-spiro [2.2] pent-1-yl, bicycloprop-2-yl group or the like. [0053] Examples of "C2-6 alkenyl group" of R ¹⁰ or the like include a vinyl group, 1-propenyl group, 2-propenyl group, 1butenyl group, 2-butenyl group, 3-butenyl group, 1-methyl group 2-propenyl, 2-methyl-2-propenyl group, 1-pentenyl group, 2-pentenyl group, group
3- pentenyl, group 4-pentenyl, group 1-methyl-2-butenyl, group 2-methyl2-butenyl, group 1-hexenyl, group 2-hexenyl, group 3-hexenyl, group
4-hexenyl, 5-hexenyl group or the like.
Examples of "C2-6 substituted alkenyl group" of R ¹⁰ or the like include a C2-6 haloalkenyl group such as a 2-chloro-1-propenyl, 2-fluoro-1-butenyl group or the like; or the like.
[0055] Examples of "C2-6 alkynyl group" of R ¹⁰ or the like include an ethynyl group, 1-propynyl group, 2-propynyl group, 1butynyl group, 2-butynyl group, 3-butynyl group, 1-methyl group 2-propynyl, 2-methyl-3-butynyl group, 1-pentynyl group, 2-pentynyl group, 3pentinyl group, 4-pentinyl group, 1-methyl-2-butynyl group, 2-methyl-3pentinyl group, group 1- hexynyl, 1,1-dimethyl-2-butynyl group or the like. [0056] Examples of "C2-6 alkynyl substituted group" of R ¹⁰ or the like include a C2-6 haloalkynyl group such as a group
4.4- dichloro-1-butynyl, 4-fluoro-1-pentynyl group, 5-bromo-2pentinyl group or the like; or the like.
Examples of C 1-6 alkoxy group of R ¹⁰ or the like include a methoxy group, ethoxy group, n-propoxy group, ipropoxy group, n-butoxy group, i-butoxy group, s-butoxy group, t-butoxy group , n-pentyloxy group, i-pentyloxy group, 2-methyl butoxy group, neopentyl group, n-hexyloxy group or the like. Among these alkoxy groups, a C3-6 alkoxy group is preferable.
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Examples of C 1-6 alkoxy group substituted by R ¹⁰ or the like include a C 1-6 haloalkoxy group such as a fluoromethoxy group, chloromethoxy group, bromomethoxy group, difluoromethoxy group, dichloromethoxy group, dibromomethoxy group, trifluoromethoxy group, trichloromethoxy group, tribromomethoxy group, 2,2,2-trifluorethoxy group, group
2.2.2- trichloroethoxy, pentafluoroethoxy group, 4-fluorbutoxy group, group
3.3.3- trifluorpropoxy, 2,2,2-trifluor-1-trifluoromethyl ethoxy group, perfluorexyloxy group or the like; a C 1-6 alkoxy hydroxy group such as a 2-hydroxyethoxy group, 2-hydroxypropoxy group or the like; a C1-6 alkoxy group C1-6 alkoxy such as a methoxymethoxy group, 1methoxyethoxy group, 2-methoxyethoxy group, ethoxymethoxy group, 1ethoxyethoxy group, 2-ethoxyethoxy group, 1-methoxy-n-propoxy group, 2methoxy-n-propoxy group , 3-methoxy-n-propoxy group or the like; a C3-8 cycloalkyl C1-6 alkoxy group such as a cyclopropyl methoxy group, cyclobutyl methoxy group, cyclopentyl methoxy group, cyclohexyl methoxy group, 2-methyl cyclopropyl methoxy group, 2,3-dimethyl cyclopropyl methoxy group, 2-cyclopropyl ethoxy group or the like; a C7-11 aralkyloxy group such as a benzyloxy group, phenethyloxy group or the like; a C1-7 acyl C1-6 alkoxy group such as an acetyl methoxy group, 2acetyl ethoxy group or the like; a C 1-6 alkoxy cyano group such as a cyanomethoxy group, 2-cyanoethoxy group or the like; a substituted C3-8 cycloalkyl C1-6 alkoxy group such as a chlorocyclohexyl methoxy group, bromocyclohexyl methoxy group, 2-methyl cyclopropyl methoxy group, 2,3-dimethyl cyclopropyl methoxy group, spiro [2.2] pent-1-yl methoxy group, group 1-methyl-spiro [2.2] pent-1-yl methoxy, group 1-hydroxymethyl spiro [2.2] pent-1-yl methoxy, group 4,4-difluoro-spiro [2.2] pent-1-yl methoxy, group bicycloprop-2-yl methoxy or the like; or the like.
Examples of "C3-8 cycloalkoxy group" of R ¹⁰ or the like include a cyclopropyloxy group, cyclobutyloxy group, cyclopentyloxy group, cyclohexyloxy group, cycloeptyloxy group or the like.
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33/134 [0060] Examples of "substituted C3-8 cycloalkyloxy group" of R ¹⁰ or the like include a chlorocyclohexyloxy group, bromocyclohexyloxy group, 2-methyl cyclopropyloxy group, 2,3-dimethyl cyclopropyloxy group, spiro group [2.2] pent- 1-yloxy, 1-methyl-spiro group [2.2] pent-1-yloxy, 1-hydroxymethyl group [2.2] pent-1-yloxy group, 4,4-difluorespiro [2.2] pent-1-yloxy group, bicyclopropyl group -2-yloxy or the like. [0061] Examples of R ¹⁰ "C2-6 alkenyloxy group" or the like include a vinyloxy group, 1-propenyloxy group, 2-propenyloxy group, 1-butenyloxy group, 2-butenyloxy group, 3-butenyloxy group, 3-methylenoxy group 2-propenyloxy, 2-methyl-2-propenyloxy group, 1-pentenyloxy group, 2-pentenyloxy group, 1-methyl-2-butenyloxy group, 2-methyl-2butenyloxy group, 3-methyl-2-butenyloxy group, group 1 -hexenyloxy, 2hexenyloxy group or the like.
Examples of "C2-6 substituted alkenyloxy group" of R ¹⁰ or the like include a C2-6 haloalkenyloxy group such as a 2-chloro-1-propenyloxy group, 3,3-dichloro-2-propenyloxy group, group 2 fluorine-butenyloxy or the like; or the like.
[0063] Examples of "C2-6 alkynyloxy group" of R ¹⁰ or the like include an ethynyloxy group, 1-propynyloxy group, 2-propynyloxy group, 1-butynyloxy group, 2-butynyloxy group, 3-butynyloxy group, group 1- methyl-2propynyloxy, 2-methyl-3-butynyloxy group, 1-pentynyloxy group, 2-pentinyloxy group, 1-methyl-2-butynyloxy group, 2-methyl-3-pentynyloxy group, 1-hexynyloxy group or the like.
[0064] Examples of "C2-6 alkynyloxy substituted group" of R ¹⁰ or the like include a C2-6 haloalkynoxy group such as a 4,4-dichloro-1-butynyloxy group, 4-fluoro-1-pentynyloxy group, group 5bromo-2-pentynyloxy or the like; or the like.
Examples of "C1-7 acyl group" of R ¹⁰ or the like include a formyl group, acetyl group, propionyl group, benzoyl group or the like.
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34/134 [0066] Examples of "C1-7 substituted acyl group" of R ¹⁰ or the like include a halogen substituted C1-7 acyl group such as a chloroacetyl, trifluoracetyl, trichloroacetyl, 4chlorobenzoyl group or the like.
Examples of "C 1-6 alkoxycarbonyl group" of R ¹⁰ or the like include a methoxycarbonyl group, ethoxycarbonyl group, n-propoxycarbonyl group, i-propoxycarbonyl group or the like.
Examples of "C1-6 alkoxycarbonyl substituted group" of R ¹⁰ or the like include a C1-6 cycloalkyl C1-6 alkoxycarbonyl group such as a cyclopropyl methoxycarbonyl group, cyclobutyl methoxycarbonyl group, cyclopentyl methoxycarbonyl group, cyclohexyl methoxycarbonyl group, group 2 -methyl cyclopropyl methoxycarbonyl, 2,3-dimethyl cyclopropyl methoxycarbonyl group, 2-chlorocyclopropyl methoxycarbonyl group, 2-cyclopropyl ethoxycarbonyl group or the like; a C1-6 haloalkoxycarbonyl group such as a fluoromethoxycarbonyl group, chloromethoxycarbonyl group, bromomethoxycarbonyl group, difluormethoxycarbonyl group, dichloromethoxycarbonyl group, dibromomethoxycarbonyl group, trifluoroethoxycarbonyl group, trichloromethoxycarbonyl group, 2,2-trichloromethoxy group 2-trichloroethoxycarbonyl, pentafluorethoxycarbonyl group, 4fluorbutoxycarbonyl group, 3,3,3-trifluorpropoxycarbonyl group, 2,2,2trifluor-1-trifluoromethyl ethoxycarbonyl group, group of fluorohexyloxycarbonyl or similar; a C6-10 aryl C1-6 alkyloxycarbonyl group such as a benzyloxycarbonyl group, 1-phenyl ethoxycarbonyl group or the like; a C 1-6 alkoxycarbonyl heterocyclyl group such as a tetrahydrofuran-2-yl methoxycarbonyl group, pyrazolyl methoxycarbonyl group, thiadiazolyl methoxycarbonyl group, pyridyl methoxycarbonyl group, pyrimidinyl methoxycarbonyl group or the like. [0069] Examples of "C3-8 cycloalkyloxycarbonyl group" of R ¹⁰ or the like include a cyclopropyloxycarbonyl group, cyclobuPetition group 870170092471, of 11/29/2017, pg. 37/143
35/134 toxicarbonyl or the like.
Examples of "C2-6 alkenyloxycarbonyl group" of R ¹⁰ or the like include an ethenyloxycarbonyl group, 2propenyloxycarbonyl group, 1-propenyloxycarbonyl group or the like. [0071] Examples of "substituted C 10-6 alkenyloxycarbonyl group of R ¹⁰ or the like include a 1-methyl-2propenyloxycarbonyl group, 2-methyl-1-propenyloxycarbonyl group or the like.
[0072] Examples of "C 10-6 alkynyloxycarbonyl group of R ¹⁰ or the like include an ethynyloxycarbonyl group, propargyloxycarbonyl group, 2-butynyloxycarbonyl group or the like.
[0073] Examples of "R ¹⁰ substituted C2-6 alkynyloxycarbonyl group or the like include a 1-methyl propargyloxycarbonyl group or the like.
[0074] Examples of "C6-10 aryloxycarbonyl group of R ¹⁰ or the like include a phenyloxycarbonyl group, naphthoxycarbonyl group or the like.
Examples of "R ¹⁰ heterocyclyloxycarbonyl group or the like include a pyridyloxycarbonyl group, pyridazinyloxycarbonyl group or the like.
[0076] Examples of "C ¹⁰ acyloxy group of R ¹⁰ or the like include a formyloxy group, acetyloxy group, propionyloxy group or the like.
Examples of "R ¹⁰ substituted C 1-7 acyloxy group or the like include a halogen substituted C 1-7 acyloxy group such as a chloroacetyloxy group, trifluoracetyloxy group, trichloroacetyloxy group, 4-chlorobenzoyloxy group; or the like; or the like.
[0078] Examples of "C ¹⁰ -6 alkoxycarbonyloxy group of R ¹⁰ or the like include a methoxycarbonyloxy group, ethoxycarbonyloxy group, i-propoxycarbonyloxy group or the like.
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36/134 [0079] Examples of "C3-8 cycloalkyloxycarbonyloxy group of R ¹⁰ or the like include a cyclopropyloxycarbonyloxy group, cyclobutyloxycarbonyloxy group, cyclopentyloxycarbonyloxy group, cyclohexyloxycarbonyloxy group or the like.
[0080] Examples of “C 10-6 alkenyloxycarbonyloxy group of R ¹⁰ or similar include one vinyloxycarbonyloxy group, group 1- propenyloxycarbonyloxy, group 2-propenyloxycarbonyloxy, group 1- butenyloxycarbonyloxy, group 2-butenyloxycarbonyloxy, group 3- butenyloxycarbonyloxy, group 1- methyl-2-propenyloxycarbonyloxide i or similar similar.[0081] Examples of “C2-6 alkynyloxycarbonyloxy group 'from R ¹⁰ or similar include one ethinyloxycarbonyloxy group, group 1- propynyloxycarbonyloxy, group 2-propynyloxycarbonyloxy, group 1- butinyloxycarbonyloxy, group 2-butynyloxycarbonyloxy, group 3-
butinyloxycarbonyloxy or the like.
Examples of "C 1-6 alkyl aminocarbonyloxy group" of R ¹⁰ or the like include a methyl aminocarbonyloxy group, dimethyl aminocarbonyloxy group, diethyl aminocarbonyloxy group, i-propyl aminocarbonyloxy group, i-butyl aminocarbonyloxy group or the like.
Examples of "C3-8 cycloalkyl aminocarbonyloxy group of R ¹⁰ or the like include a cyclopropyl aminocarbonyloxy group, cyclobutyl aminocarbonyloxy group, cyclopentyl aminocarbonyloxy group, cyclohexyl aminocarbonyloxy group or the like.
[0084] Examples of “C 10-6 alkenyl aminocarbonyloxy group of R ¹⁰ or the like include a vinyl aminocarbonyloxy group, 1propenyl aminocarbonyloxy group, 2-propenyl aminocarbonyloxy group, 1butenyl aminocarbonyloxy group or the like.
[0085] Examples of "C2-6 alkynyl aminocarbonyloxy group of R ¹⁰ or the like include an ethinyl aminocarbonyloxy group, 1propynyl aminocarbonyloxy group, 2-propynyl aminocarbonyloxy group, group 1 Petition 870170092471, 29/11/2017, pg. 39/143
37/134 butinyl aminocarbonyloxy or the like.
[0086] Examples of "C6-10 aryl aminocarbonyloxy group of R ¹⁰ or the like include an anilinocarbonyloxy group, naphthyl aminocarbonyloxy group or the like.
Examples of "R ¹⁰ heterocyclyl aminocarbonyloxy or the like include a pyridyl aminocarbonyloxy group, pyridazinyl aminocarbonyloxy group or the like.
Examples of "R ¹⁰ substituted aminooxy or the like include a C1-6 alkyl aminooxy group such as a methyl aminooxy group, ethyl aminooxy group or the like; a C1-7 acyl aminooxy group such as a formyl aminooxy group, acetyl aminooxy group or the like; or the like.
[0089] Examples of "R ¹⁰ C1-6 alkylidene aminooxy group of R ¹⁰ or the like include an aminooxymethylidene group, aminooxyethylidene group, n-propylidene aminooxy group, i-propylidene aminooxy group, n-butylidene aminooxy group, i-butylidene aminooxy group , aminooxybutylidene group or the like.
[0090] Examples of "C6-10 aryl group of R ¹⁰ or similar are the same as those listed as examples of Cy1 or similar.
[0091] Examples of “heterocyclyl group of R ¹⁰ or similar are the same as those listed as examples of Cy1 or similar.
[0092] Examples of "C ^10-10 aryloxy group of R ¹⁰ or the like include a phenoxy group, naphthoxy group or the like.
[0093] Examples of "R ¹⁰ heterocyclyloxy or the like include a pyridyloxy group, pyridazinyloxy group or the like.
Examples of "R ¹⁰ substituted sulfonyloxy or the like include a C1-6 alkyl sulfonyloxy group such as a methyl sulfonyloxy group, ethyl sulfonyloxy group or the like; a C1-6 haloalkyl group
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38/134 sulfonyloxy such as a trifluoromethyl sulfonyloxy group, 2,2,2trifluorethyl sulfonyloxy group or the like; a C6-10 aryl sulfonyloxy group such as a phenyl sulfonyloxy group or the like; or the like. [0095] Examples of "C ¹⁰ -6 alkyl group of R ¹⁰ or the like include a methyl amino group, dimethyl amino group, diethyl amino group, i-butyl amino group or the like.
[0096] Examples of "C 10-8 cycloalkyl amino group of R ¹⁰ or the like include a cyclopropyl amino group, cyclobutyl amino group, cyclopentyl amino group, cyclohexyl amino group or the like.
[0097] Examples of "C 10-6 alkenyl amino group of R ¹⁰ or the like include a vinyl amino group, 1-propenyl amino group, 2-propenyl amino group, 1-butenyl amino group or the like.
[0098] Examples of "R ¹⁰ C2-6 alkynyl group of R ¹⁰ or the like include an ethynyl amino, 1-propynyl amino, 2-propynyl amino, 1-butynyl amino group or the like.
[0099] Examples of "C ^10-10 aryl amino group of R ¹⁰ or the like include an anilino, naphthyl amino group or the like.
Examples of "R ¹⁰ heterocyclyl amino group or the like include an amino pyridyl group, amino pyridazinyl group or the like.
Examples of "R ¹⁰ -substituted hydroxy group or the like include a C 1-6 alkoxy group such as a methoxy amino group, ethoxy amino group or the like; a C1-7 acyloxyamino group such as an acetoxy amino group, propionyloxy amino group or the like; or the like.
Examples of "R ¹⁰ C 1-7 acyl amino group of R ¹⁰ or the like include a formyl amino group, acetyl amino group, propanoyl amino group butyryl amino group, i-propyl carbonyl amino group, benzoyl amino group or the like.
[00103] Examples of "C1-6 alkoxycarbonyl amino group of R ¹⁰ or
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Similar 39/134 include a methoxycarbonyl amino group, an ethoxycarbonyl amino group, a n-propoxycarbonyl amino group, an i-propoxycarbonyl amino group or the like.
Examples of "C 10-6 alkenyloxycarbonyl amino group of R ¹⁰ or the like include a vinyl aminocarbonyl amino group, 1propenyl aminocarbonyl amino group, 2-propenyl aminocarbonyl amino group, 1-butenyl aminocarbonyl amino group or the like.
Examples of "R ¹⁰ C2-6 alkynyloxycarbonyl amino group of R ¹⁰ or the like include an ethinyl aminocarbonyl amino group, 1propynyl aminocarbonyl amino group, 2-propynyl aminocarbonyl amino group, 1-butynyl aminocarbonyl group or the like.
[00106] Examples of "C ^10-10 aryloxycarbonyl amino group of R ¹⁰ or the like include an anilinocarbonyl amino group, naphthyl aminocarbonyl amino group or the like.
Examples of "R ¹⁰ heterocyclyloxycarbonyl amino group or the like include an aminocarbonyl amino pyridyl group, amino aminocarbonyl pyridazinyl group or the like.
Examples of "R ¹⁰ substituted amino sulfonyl group or the like include a C 1-6 alkyl sulfonyl amino group such as a methyl sulfonyloxy amino group, ethyl sulfonyl amino group or the like; a C1-6 haloalkyl sulfonyl amino group such as a trifluoromethyl sulfonyl amino group, 2,2,2-trifluorethyl sulfonyl amino group or the like; a C6-10 aryl sulfonyl amino group such as a phenyl sulfonyl amino group or the like; or the like.
Examples of "R ¹⁰ substituted aminocarbonyl group or the like include a dimethyl aminocarbonyl group, phenyl aminocarbonyl group, N-phenyl-N-methyl aminocarbonyl group or the like. [00110] Examples of "C ¹⁰ -6 alkyl thio group of R ¹⁰ or the like include a methyl thio group, ethyl thio group, n-propyl thio group, ipropyl thio group, n-butyl thio group, i-butyl thio group, group s-butyl thio, t-butyl group
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40/134 uncle, or the like.
[00111] Examples of "C 10-8 cycloalkyl thio group of R ¹⁰ or the like include a cyclopropyl thio group, cyclobutyl thio group, cyclopentyl thio group, cyclohexyl thio group, cycloeptyl thio group, or the like. [00112] Examples of “C 10-6 alkenyl thio group of R ¹⁰ or the like include a vinyl thio group, 1-propenyl thio group, 2-propenyl thio group, 1-butenyl thio group, 2-butenyl thio group, group 3- butenyl thio or the like.
[00113] Examples of "C 10-6 alkynyl thio group of R ¹⁰ or the like include an ethinyl thio group, 1-propynyl thio group, 2-propynyl thio group, 1-butynyl thio group, 2-butinyl thio group, group 3- butinyl thio or the like.
ethyl (thiocarbonyl), propyl group (thiocarbonyl), group [00114] Examples of "C 6-10 aryl thio group of R ¹⁰ or the like include a phenyl thio group, thio naphthyl group or the like.
[00115] Examples of "R ¹⁰ heterocyclyl group or the like include a pyridyl thio group, pyridazinyl thio group or the like.
[00116] Examples of "R ¹⁰ (C1-6 alkyl) thiocarbonyl group or the like include a methyl group (thiocarbonyl), n-propyl group (thiocarbonyl), in-butyl group (thiocarbonyl), ibutyl group (thiocarbonyl), group s-butyl (thiocarbonyl), t-butyl (thiocarbonyl) group or the like.
[00117] Examples of “R ¹⁰ (C1-6 alkoxy) thiocarbonyl group or the like include a methoxy group (thiocarbonyl), ethoxy group (thiocarbonyl), n-propoxy group (thiocarbonyl), ipropoxy group (thiocarbonyl), n- group butoxy (thiocarbonyl), ibutoxy group (thiocarbonyl), s-butoxy group (thiocarbonyl), t-butoxy group (thiocarbonyl) or the like.
[00118] Examples of “R ¹⁰ (C1-6 alkylthio) carbonyl group or the like include a (methyl thio) carbonyl group, group (ethyl
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41/134 thio) carbonyl, group (n-propyl thio) carbonyl, group (i-propyl thio) carbonyl, group (n-butyl thio) carbonyl, group (i-butyl thio) carbonyl, group (s-butyl thio) carbonyl, (t-butyl thio) carbonyl group or the like.
[00119] Examples of “R ¹⁰ (C1-6 alkylthio) thiocarbonyl group or the like include a thiocarbonyl (methyl thio) group, group (ethyl
uncle) thiocarbonyl, group (n-propyl uncle) thiocarbonyl, group (i-propyl uncle) thiocarbonyl, group (n-butyl uncle) thiocarbonyl, group (i-butyl uncle) thiocarbonyl, group (s-butyl uncle) thiocarbonyl, group (t-butyl
thio) thiocarbonyl or the like.
Examples of "sulfinyl group substituted by R ¹⁰ or the like include a C 1-6 alkyl sulfinyl group such as a methyl sulfinyl group, ethyl sulfinyl group or the like; a C1-6 haloalkyl sulfinyl group such as a trifluoromethyl sulfinyl group, 2,2,2-trifluorethyl sulfinyl group or the like; a C6-10 aryl sulfinyl group such as a phenyl sulfinyl group or the like; or the like.
[00121] Examples of "substituted sulfonyl group of R ¹⁰ or the like include a C 1-6 alkyl sulfonyl group such as a methyl sulfonyl group, ethyl sulfonyl group or the like; a C1-6 haloalkyl sulfonyl group such as a trifluoromethyl sulfonyl group, 2,2,2-trifluorethyl sulfonyl group or the like; a C6-10 aryl sulfonyl group such as a phenyl sulfonyl group or the like; a C1-6 alkoxysulfonyl group such as a methoxysulfonyl group, ethoxysulfonyl group or the like; or the like.
[00122] Examples of "a trisubstituted silyl group with C 1-6 alkyl of R ¹⁰ or the like include a trimethyl silyl group, triethyl silyl group, t-butyl dimethyl silyl group or the like.
[00123] Examples of "a silyl group tri-substituted with C6-10 aryl of R ¹⁰ or the like include a triphenyl silyl group or the like.
[00124] Examples of “halogen atom” of R ¹⁰ or similar
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42/134 include a chlorine atom, a bromine atom, a fluorine atom, an iodine atom or the like.
[00125] R ¹⁰ and R ¹¹ of Cy ¹ can independently form a ring, or be linked to form a ring, or bond with the atoms that constitute Cy ¹ to form a ring; R ²⁰ and R ²¹ of Cy ² can independently form a ring, or be linked to form a ring, or they can bond with the atoms that make up Cy ² to form a ring.
[00126] Examples of ring that can be formed include an aromatic hydrocarbon ring such as a benzene ring or the like; a C5-7 cycloalkene ring such as a cyclopentene ring, cyclohexene ring, cycloepene ring or the like; a 5- to 7-membered aromatic hetero ring such as a furan ring, thiophene ring, pyrrole ring, imidazole ring, pyrazole ring, thiazole ring, oxazole ring, isoxazole ring, pyridine ring, pyrazine ring , pyrimidine ring, pyridazine ring, azepine ring, diazepine ring or the like; a 5- to 7-membered unsaturated hetero ring such as a dihydro-2H-pyran ring, dihydro-2H-thiopyran ring, tetrahydropyridine ring or the like; or the like.
[00127] These rings may have substituents on the rings.
[00128] Examples of substituents include a halogen atom such as a fluorine atom, chlorine atom, bromine atom, iodine atom or the like; a C1-6 alkyl group such as a methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, s-butyl group, i-butyl group, t-butyl group, n-pentyl group, n-hexyl group or the like; a C3-6 cycloalkyl group such as a cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group or the like; a C1-6 alkoxy group such as a methoxy group, ethoxy group, n-propoxy group, i-propoxy group, n-butoxy group, s-butoxy group, ibutoxy group, t-butoxy group, or the like; a hydroxy group; a group
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C1-6 haloalkyl such as a chloromethyl group, chloroethyl group, trifluoromethyl group, 1,2-dichloro-n-propyl group, 1-fluoro-n-butyl group, perfluoro-n-pentyl group or the like; or the like.
[00129] In formula (I), R ¹⁰ preferably represents a C1-6 alkyl group, a C1-6 alkoxy C1-6 alkyl group, a C1-6 alkoxy C1-6 alkoxy C1-6 alkyl alkoxy, a C2- 6 alkenyl, a hydroxy group, a C1-6 alkoxy group, a C1-6 haloalkoxy group, a C3-8 cycloalkoxy group, a C2-6 alkenyloxy group, a C2-6 haloalkenyloxy group, a C2-6 alkoxy group, an C2-6 haloalkynoxy group, a C1-6 alkoxy C1-6 alkoxy group, a C3-8 cycloalkyl C1-6 alkoxy group, a cyano C1-6 alkoxy group, a C1-7 acyl C1-6 alkoxy group, a hydroxy group C1-6 alkoxy, a C1-7 acyloxy group, a C1-6 alkoxycarbonyl group, a C2-6 alkenyloxycarbonyl group, a C2-6 alkynyloxycarbonyl group, a C1-6 alkoxycarbonyloxy group, a C1-6 alkyl aminocarbonyloxy group, a group C6-10 aryl, a heterocyclyl group, a C1-6 haloalkyl sulfonyloxy group, a C1-6 alkylidene aminooxy group, a C1-6 alkoxycarbonyl amino group, an unsubstituted or substituted C7-11 aralkyl group, a C7-11 aralkyloxy group not substituted or substituted, a C 1-6 alkylthio group or a nitro group.
[00130] In formula (I), R ¹¹ preferably represents a cyano group, a halogen atom, pentafluorsulfanyl, a C1-6 haloalkyl group, a C2-6 haloalkenyl group, or a C2-6 haloalkynyl group.
[00131] In formula (I), R ²⁰ preferably represents a cyano group, a halogen atom, pentafluorsulfanyl, a C1-6 haloalkyl group, a C2-6 haloalkenyl group, or a C2-6 haloalkynyl group.
[00132] In formula (I), R ²¹ preferably represents a C1-6 alkyl group, a C1-6 alkoxy C1-6 alkyl group, a C1-6 alkoxy group C1-6 alkoxy C1-6 alkyl, a hydroxy group, a C1-6 alkoxy group, a
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44/134 C1-6 haloalkoxy group, a C2-6 haloalkenyloxy group, a C2-6 haloalkynoxy group, a C1-6 alkoxy C1-6 alkoxy group, a C3-8 cycloalkyl C1-6 alkoxy group, a C1-6 group alkoxycarbonyl, a C2-6 alkenyloxycarbonyl group, a C2-6 alkynyloxycarbonyl group, a C16 alkylidene aminooxy group, a C1-6 alkoxycarbonyl amino group, an unsubstituted or substituted C7-11 aralkyloxy group, an unsubstituted or substituted C7-11 aralkyloxy group substituted, or a nitro group.
[00133] In formula (I), Y represents an oxygen atom or a sulfur atom.
Chemical formula 8
R-
R (I) [00134] In the cyclic amine compound of the present invention, it is preferable that Cy ¹ is a phenyl group, Cy ² is a pyridin-2-yl group, R ^1b , R ^2b , R ^3a , R ^3b , R ^4a , R ^4b , and R ^5a are hydrogen atoms, R ^1a and R ^2a bond to form an unsubstituted or substituted C3-6 alkylene group, a substituted or substituted C3-6 alkenylene group, a group represented by the formula: - CH2OCH2, a group represented by the formula: -CH2SCH2-, a group represented by the formula: -CH2C (= O) CH2-, or a group represented by the formula: -CH2NR ⁶ CH2- (provided that R ⁶ is a hydrogen atom, an unsubstituted or substituted C1-6 alkyl group, an unsubstituted or substituted C1-7 acyl group or an unsubstituted or substituted C1-6 alkoxycarbonyl group), Y is an oxygen atom, r is 0, and p is an integer from 0 to 4. In other words, the cyclic amine compound of the present invention is preferably a cyclic amine compound represented by formula (II).
Chemical formula 9
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[00135] In addition, R ¹⁰ , m, R ¹¹ , n and R ²⁰ of formula (II) are the same as previously defined in formula (I). In formula (II), p 'represents the number of R ²⁰ and represents an integer from 0 to 4. When p' is 2 or more, R ²⁰ s can be the same or different. In formula (II), A represents an unsubstituted or substituted C3-6 alkylene group, an unsubstituted or substituted C3-6 alkenylene group, a group represented by the formula: -CH2OCH2-, a group represented by the formula: -CH2SCH2-, a group represented by the formula: CH2C (= O) CH2- or a group represented by the formula: -CH2NR ⁶ CH2 (provided that R ⁶ represents a hydrogen atom, an unsubstituted or substituted C1-6 alkyl group, a C1- group 7 unsubstituted or substituted acyl or an unsubstituted or substituted C1-6 alkoxycarbonyl group).
Compound of cyclic amine salt [00136] There are no particular limitations on the salts of the cyclic amine compound of the present invention, as long as they are agriculturally and horticulturally acceptable salts. Examples of salt include salts of inorganic acids such as hydrochloric acid or sulfuric acid; organic acid salts such as acetic acid or lactic acid; alkali metal salts such as lithium, sodium or potassium; alkaline earth metal salts such as calcium or magnesium; salts of transition metals such as iron and copper; and salts of organic bases such as ammonia, triethylamine, tributylamine, pyridine or hydrazine. The salt of the cyclic amine compound of the present invention can be produced by a well known method using the cyclic amine compound represented by formula (I) or (II).
Production Method
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46/134 [00137] There are no particular limitations on the production method of the cyclic amine compound or its salt.
[00138] Initially, a method of producing a hydroxylamine compound of the present invention, where Y is an oxygen atom, will be explained. When Y is an oxygen atom, the production method that passes through a compound represented by the following formula (3) as an intermediate is preferable.
Chemical formula 10
[00139] Initially, a secondary amine compound, represented by formula (1) (hereinafter referred to as "compound (1)") is prepared. An aminooxy compound represented by formula (2) (hereinafter referred to as "compound (2)") can be synthesized by oxidizing compound (1) with a suitable oxidizing agent. Specific examples of an oxidation reaction method include a method in which an oxidizing agent such as hydrogen peroxide, sodium hypochlorite or an organic oxidizing agent is allowed to act in a suitable solvent, such as an anhydrous or hydrated alcohol such as methanol, ethanol , propanol or isopropanol, an ether such as dioxane or tetrahydrofuran (THF) or acetonitrile and a
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47/134 method in which a tungstate-hydrogen peroxide and urea complex is left to act. In addition, another example of a method that can be used includes inflating a gas containing oxygen or active oxygen such as ozone in a reaction mixture.
[00140] Then, the aminooxy group is converted to a hydroxylamino group by reducing the compound (2) under suitable conditions. A hydroxylamino compound represented by formula (3) (hereinafter referred to as "compound (3)") is formed by this reduction reaction.
[00141] After the reduction reaction, a heterocyclyl halide is reacted with compound (3) in the presence of a base. As a result, a heterocyclyloxyamine compound represented by formula (4) can be obtained. This reaction is described, for example, in U.S. Patent No. 5,286,865.
[00142] Additionally, in the formulas (1) to (4) mentioned above, R _b represents a substituted phenyl group, R _a represents a substituted heterocyclyl group and X represents a halogen atom.
[00143] Additionally, compound (3) can also be obtained, for example, by the production method indicated below.
Chemical formula 11
[00144] An alkyl amino compound represented by the formula (2 ') (hereinafter referred to as a "compound (2')") is obtained by NPetição 870170092471, of 29/11/2017, p. 50/143
48/134 alkylation of the aforementioned compound (1) with acrylonitrile. Then, compound (3) can be obtained by oxidation with a suitable oxidizing agent to obtain a form of N-oxide within the reaction system and then subjecting it to a Cope elimination reaction. This reaction is described, for example, in Tetrahedron Letters, 48 (2007), pp. 1683-1686.
[00145] On the other hand, the compound of the present invention, where Y is a sulfur atom can be produced by the following production method.
Chemical formula 12
SO2Cl2
Ra-SR '(5)
Ra-S-Cl (1)
Base
[00146] Initially, a sulfenyl compound represented by formula (5) (hereinafter referred to as "compound (5)") (in the formula, R 'represents a hydrogen atom or a benzyl group) is prepared. Then, sulfuryl chloride is added and reacted with the compound (5) to obtain a sulfenyl chloride compound, followed by the reaction of the compound (1) in the presence of a base to obtain a heterocyclyloxyamine compound represented by the formula (6). The production method of the sulfenyl chloride compound is described in Synthesis 1994, volume 1994 (1): 21-22.
Hydroxylamine Compound [00147] The hydroxylamine compound according to the present invention is a compound represented by the formula (III). In addition, the salt of the hydroxylamine compound according to the present invention is a salt of the compound represented by formula (III). A compound represented by formula (III) or a salt thereof is preferable as a production intermediate for a compound represented by Petition 870170092471, of 11/29/2017, p. 51/143
49/134 by formula (I) or formula (II) or a salt thereof.
[00148] In formula (III), Cy ¹ , R ¹⁰ , R ¹¹ , m, n, R ^1a , R ^1b , R ^2a , R ^2b , R ^3a , R ^3b , R ^4a , R ^4b and R ^5a are the same as previously defined in formula (I).
[00149] In formula (III), R ^1a and R ^2a , or R ^3a and R ^4a linked together form an unsubstituted or substituted C3-6 alkylene group, an unsubstituted or substituted C3-6 alkenylene group, a group represented by formula: -CH2OCH2-, a group represented by the formula: -CH2SCH2-, a group represented by the formula: -CH2C (= O) CH2or a group represented by the formula: -CH2NR ⁶ CH2- (provided that R ⁶ represents a hydrogen atom , an unsubstituted or substituted C1-6 alkyl group, an unsubstituted or substituted C1-7 acyl group or an unsubstituted or substituted C1-6 alkoxycarbonyl group). Examples of such divalent organic groups are the same as previously defined in formula (I).
[00150] In formula (III), Cy ¹ is preferably a phenyl group, a pyrazolyl group, a thiadiazolyl group, a pyridyl group, a pyrimidinyl group or a pyridazinyl group.
[00151] In formula (III), R ¹⁰ preferably represents a C1-6 alkyl group, a C1-6 alkoxy C1-6 alkyl group, a C1-6 alkoxy C1-6 alkoxy C1-6 alkyl alkoxy, a C2- 6 alkenyl, a hydroxy group, a C1-6 alkoxy group, a C1-6 haloalkoxy group, a C3-8 cycloalkoxy group, a C2-6 alkenyloxy group, a C2-6 haloalkenyloxy group, a C2-6 alkoxy group, an C2-6 haloalkynoxy group, a C1-6 alkoxy C1-6 alkoxy group, a C3-8 cycloalkyl C1-6 alkoxy group, a cyano C1-6 alkoxy group, a C1-7 acyl C1-6 alkoxy group, to C1 hydroxy -6 alkoxy, a C1-7 acyloxy group, a C1-6 alkoxycarbonyl group, a C2-6 alkenyloxycarbonyl group, a C2-6 alkynyloxycarbonyl group, a C1-6 alkoxycarbonyloxy group, a C1-6 alkyl aminocarbonyloxy group, a C6 group -10 aryl, a heterocyclyl group, a C1-6 haloalkyl group
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50/134 sulfonyloxy, a C1-6 alkylidene aminooxy group, a C1-6 alkoxycarbonyl amino group, an unsubstituted or substituted C7-11 aralkyl group, an unsubstituted or substituted C7-11 aralkyloxy group, a C1-6 alkylthio group or a nitro group.
[00152] In formula (III), R ¹¹ preferably represents a cyano group, a halogen atom, a pentafluorsulfanyl group, a C1-6 haloalkyl group, a C2-6 haloalkenyl group, or a C2-6 haloalkynyl group.
[00153] There are no particular limitations to the salt of the hydroxylamine compound according to the present invention as long as it does not inhibit the reaction with the heterocyclyl halide in the presence of a base. Examples of salts include alkali metal salts such as lithium salts, sodium salts or potassium salts. A hydroxylamine compound salt according to the present invention can be obtained by a well known method using a hydroxylamine compound represented by formula (III).
[00154] As the cyclic amine compound of the present invention or its salt demonstrates insecticidal action on adult insects, immature insects, larvae, insect eggs and the like, it can be used to control harmful organisms such as harmful insects present in agricultural crops , mites, ticks, insects harmful to health, insects harmful to stored grains, insects harmful to clothes and insects harmful to the home environment. [00155] Examples of insects include the following:
Lepidopteran pests such as, for example, Spodoptera litura, Mamestra brassicae, Agrotis ipsilon, green caterpillars, Autographa nigrisigna, Plutella xylostella, Adoxophyes honmai, Homona magnanima, Carposina sasakii, Grapholita molesta, Phyllocnistia the citrella, ringtone, Tyylloctria Euproctis pseudoconspersa, Chilo suppressalis, Cnaphalocrocis medinalis, OsPetição 870170092471, of 11/29/2017, p. 53/143
51/134 trinia nubilasis, Hyphantria cunea, Cadra cautella, genus Heliothis, genus Helicoverpa, genus Agrothis, Tinea translucens, Cydia pomonella, and Pectinophora gossypiella;
Hemiptera pests such as, for example, Myzus persicae, Aphis gossypii, Lipaphis erysimi, Rhopalosiphum padi, Riptortus clavatus, Nezara antennata, Unaspis yanonensis, Pseudococcus comstocki, Trialeurodes vaporariorum, Bemisia pyris, Stephanie Laodelphax stratella, Sogatella furcifera, and Nephotettix cincticeps;
Coleoptera pests such as, for example, Phyllotreta striolata, Aulacophora femoralis, Leptinotarsa decemlineata, Lissorhoptrus oryzophilus, Sitophilis zeamais, Callosobruchus chinensis, Popillia japonica, Anomala rufocuprea, genus Diabrotis, geniodic, Briodocera, geniodic, Geniodus, Briodica, Epilachna vigintioctopunctata, Tenebroides mauritanicus, and Anthonomus grandis;
Diptera pests such as, for example, Musca domestica, Calliphora lata, Boettcherisca peregrine, Zeugodacus cucurbitae, Bactrocera dorsalis, Delia platura, Agromyza oryzae, Drosophila melanogaster, Stomoxys calcitrans, Culex tritaeniorhynisis, Aedes;
Herbal pests such as, for example, Thrips palmi and Scirtothrips dorsalis;
Hymenopteran pests such as, for example, Monomorium pharaonis, Vespa simillima xanthoptera, and Athalia rosae ruficornis;
Orthopteran pests such as, for example, Locusta migratoria, Blattella germanica, Periplaneta americana, and Periplaneta fuliginosa;
Isopteran pests such as, for example, Coptotermes formosanus and Reticulitermes speratus;
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Siphonapter pests such as, for example, Pulex irritans and Ctenocephalides felis; ftiráptera pests such as, for example, Pediculus humanus;
Nematode plant parasites such as Meloidogyne incognita, Pratylenchus spp., Heterodera glycines, Aphelenchoides besseyi, and Bursaphelenchus xylophilus; and mites.
[00156] Among these insects, the cyclic amine compound of the present invention or salt thereof is useful as an active ingredient in an acaricide since it is particularly effective in controlling mites. [00157] Examples of mites intended for control are indicated below:
Mites belonging to the Tetranychidae family, including Brevipalpus lewisi, Brevipalpus obovatus, Brevipalpus phoenicis, praetiosa Bryobia, rubrioculus Bryobia, Dolichotetranychus floridanus, Eotetranychus boreus, Eotetranychus geniculatus Eotetranychus pruni, Eotetranychus sexmanaculatus, Eotetranychus smithi, Eotetranychus uncatus, Oligonychus hondoensis, Oligonychus ilicis Oligonychus karamatus, Oligonychus shinkajii, Panonychus citri, Panonychus mori, Panonychus ulmi, Tenuipalpus zhizhilashviliae, Tetranychus cinnabarinus, Tetranychus kanzawai, Tetranychus urticae, Tetranychus viennensis or Tetranychus viennensis or Tetranychus viennensisucker or Tennetusucker;
Dust mites that belong to the Eriophydae family, such as Acaphylla theavagrans, Aceria paradianthi, Aceria tulipae, Aculops lycopersici, Aculops pelekassi, Aculus fockeui, Aculus schlechtendali, Calacarus carinatus, Calepitrimerus vitis, Colomerusio pisis, Epicusio chisis;
Mites that belong to the Astigmata family, such as Acarus siro, Aleuroglyphus ovatus, Carpoglyphus lactis, Lardoglyphus konoi, Rhizoglyphus echinopus, Rhizoglyphus robini, Tyrophagus putrescentiae or Tyrophagus similis;
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Mites that belong to the family Tarsonemidae, such as
Phytonemus pallidus, Polyphagotarsonemus latus, Tarsonemus bilobatus or Tarsonemus waitei;
Mites that belong to the Eupodidae family, such as Penthaleus erythrocephalus or Penthaleus major;
Mites that belong to the Ixodidae family, such as Haemaphysalis longicornis, Haemaphysalis japonica, Boophilus microplus, Dermacentor recticulatus, Dermacentor taiwanensis, Haemaphysalis flava, Ixodes ovatus, Ixodes persulcatus, Dermacentor reticulatus or similar.
[00158] Additionally, resistant mites that have resistance to conventionally known acaricides are also included in the mite examples above.
[00159] The cyclic amine compound of the present invention or its salt causes little chemical damage, demonstrates low levels of toxicity in warm-blooded fish and animals and is a compound that has a particularly high degree of safety.
Acaricide [00160] The acaricide of the present invention contains as an active ingredient at least one type selected from the group consisting of a cyclic amine compound represented by formula (I) or formula (II) or a salt thereof. In the acaricide of the present invention, one type of the cyclic amine compound represented by formula (I) or formula (II) or a salt thereof can be contained alone or two or more types can be contained in combination.
[00161] In addition, although the acaricide of the present invention may contain only the cyclic amine compound represented by formula (I) or formula (II) of the present invention or a salt thereof, it may also contain a vehicle such as a vehicle solid, liquid vehicle or gaseous vehicle. Additionally, the acaricide of this
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The invention may have the cyclic amine compound represented by formula (I) or formula (II) or a salt thereof impregnated in a base material such as a porous ceramic plate or fabric
TNT. In addition, a surfactant or other adjunct can be added if necessary.
[00162] The acaricide according to the present invention can be formulated in a form capable of being typically adopted by agricultural chemists, in other words, in the form of a water-dispersible powder, granules, powder, emulsion, water-soluble powder, suspension, water-dispersible granular powder, fluidizable preparation, aerosol, mist, heat-sweating agent, fumigant, poisonous bait or microcapsules.
[00163] Examples of additives and vehicles used when formulating a solid preparation include vegetable powders such as soy powder or flour, fine mineral powders such as diatomaceous earth, apatite, plaster, talc, bentonite, pyrophyllite or clay; and organic and inorganic compounds such as sodium benzoate, urea or sodium sulfate. [00164] Examples of solvents used when formulating liquid preparations include petroleum fractions such as kerosene, xylene or naphtha solvent; cyclohexane, cyclohexanone, dimethylformamide, dimethylsulfoxide, alcohols, acetone, methyl isobutyl ketone, mineral oils, vegetable oils and water.
[00165] Examples of gaseous vehicles used when formulating propellants include butane gas, LPG, dimethyl ether and carbon dioxide gas.
[00166] Examples of base materials for poisonous bait include components for baits such as grain powder, vegetable oil, sugar or crystalline cellulose, antioxidants such as dimethylhydroxytoluene or nordihydroguaiaretic acid, preservatives such as dehydroacetic acid, substances that prevent accidental ingestion by children pePetition 870170092471, of 11/29/2017, p. 57/143
55/134 pet and pets such as cayenne pepper powder, attractive insect fragrances such as cheese odor or onion odor.
[00167] A surfactant can be added in order to obtain a stable and uniform form during formulation. Examples of surfactants include nonionic surfactants such as polyoxyethylene alkyl ethers, polyoxyethylene higher fatty acid esters, polyoxyethylene sorbitan higher fatty acid esters or polyoxyethylene phenyl tristyryl ethers, polyoxyethylene ethylene sulfonates, phenylalkylsulfonates, polyoxyethylene sulfates and alkali sulfates. , lignin sulfonates, condensates of alkylnaphthalene sulfonates formaldehyde and isobutylene-maleic anhydride copolymers.
[00168] In the case of using the acaricide of the present invention in agricultural applications, the content of the cyclic amine compound of the present invention or salt thereof in a preparation is preferably from 0.01% by weight to 90% by weight and more preferably from 0.05% by weight to 85% by weight.
[00169] An acaricide for agricultural use that is supplied in the form of a water-dispersible powder, emulsion, suspension, fluidizable preparation, water-soluble powder or water-dispersible granular powder can be prepared in the form of a solution, suspension or emulsion by dilution to a prescribed concentration in water and then sprayed on plants or soil. In addition, an acaricide for agricultural use that is supplied in the form of a powder or granules can be sprayed directly onto plants or soil.
[00170] Additionally, an epidemic prevention acaricide that is supplied in the form of an emulsion, water dispersible powder or fluidizable preparation and the like can be applied by dilution to a prescribed concentration with water. In addition, an epidemic prevention mite killer that is provided as a solution
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56/134 oily, aerosol, mist, poisoned bait or mite plaques can be used directly.
[00171] In the case of using the acaricide of the present invention to control parasitic mites of farm animals such as cows or pigs and pets such as dogs and cats, the compound of the present invention can be used in a ratio of 0, 01 mg to 1000 mg per kg of host animal.
[00172] An acaricide to control parasitic animal mites can be applied using a known veterinary method. Examples of such methods include methods in which acaricide is administered to an animal via a tablet, capsule, immersion in liquid, food additive, suppository or injection (intramuscular, subcutaneous, intravenous or intra-abdominal injection) when administered for the purpose of systemic control, methods in which an oily or aqueous preparation is administered by spraying, dripping or localized, when administered for the purpose of non-systemic control and methods in which the mite is mixed with a resin and the mixed product is molded into a suitable form such as that of a collar or ear seal that is then attached to the animal.
[00173] The acaricide of the present invention can be mixed or used in combination with fungicides, other insecticides or acaricides, nematicides, soil pesticides, plant regulators, synergists, fertilizers, soil improvers or animal feed and the like.
[00174] The following are typical examples of fungicides, other insecticides or acaricides, nematocides, soil pesticides and plant regulators capable of being used by mixing with the compound of the present invention.
[00175] Fungicides:
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1) based on benzimidazole: benomyl, carbendazim, fuberidazole, thiabendazole, methyl thiophanate or the like;
2) dicarboxyimide-based fungicides: clozolinate, iprodione, procymidone, vinclozoline or the like;
3) DMI fungicides: imdazalil, oxpoconazole, pefurazoate, prochloraz, triflumizole, triforin, pyrifenox, fenarimol, nuarimol, azaconazole, bitertanol, bromoconazole, cyproconazol, diphenoconazole, diniconazol, flucazazol, epoxazazol, flucazazol, epoxy , metconazole, miclobutanil, penconazole, propiconazole, protioconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole, etaconazole, furconazole-cis or the like;
4) phenylamide-based: benalaxyl, furalaxil, metalaxyl, metalaxyl-M, oxadixyl, ofurace or the like;
5) amine-based: aldimorph, dodemorph, fenpropimorph, tridemorph, phenpropidine, piperalin, spiroxamine or the like;
6) based on phosphotiolate: EDDP, iprobenfos, pyrazophos or the like;
7) based on dithiolane: isoprothiolane or the like;
8) based on carboxamide: benodanil, boscalid, carboxine, fenfuran, flutolanil, furametpir, mepronil, oxycarboxine, pentiopirad, tifluzamide or the like;
9) based on hydroxy (2-amino) pyrimidine: bupirimate, dimethyrimol, ethyrimole or the like;
10) AP fungicides (based on anilinopyrimidines): cyprodinil, mepanipyrim, pyrimethanil or similar;
11) based on N-phenylcarbamate: dietofencarb or the like;
12) QoI fungicides (based on Qo inhibitor): azoxyestrobin, picoxyestrobin, pyraclostrobin, kresoxim-methyl, trifloxystroPetition 870170092471, of 11/29/2017, p. 60/143
58/134 bina, dimoxyestrobina, metominostrobina, orisastrobina, famoxadone, fluoxastrobina, fenamidone, metominofeno or similar;
13) PP fungicides (based on phenylpyrrole): fenpiconil, fludioxonil or similar;
14) based on quinoline: quinoxyphen or the like;
15) AH fungicides (based on aromatic hydrocarbon): biphenyl, chloroneb, dichloran, quintozene, tecnazene, tolclofos-methyl or similar;
16) based on MBI-R: phthalide, pyroquinone, tricyclazole or the like;
17) based on MBI-D: carpropamid, diclocimet, phenoxanil or the like;
18) SBI agents: fenhexamid, pyributicarb, terbinafine or the like;
19) phenylureas: pencicuron or similar;
20) Qil fungicides (Qi inhibitors): cyazofamid or the like;
21) based on benzamide: zoxamide or the like;
22) based on enopyranurone: blasticidine, mildiomycin or the like;
23) based on hexopyranosil: kasugamacin or similar;
24) based on glucopyranosyl: streptomycin, validamycin or the like;
25) based on cyanoacetoamide: cymoxanil or the like;
26) based on carbamate: idocarb, propamocarb, protiocarb, polycarbamate or the like;
27) non-coupling agents: binapacril, dinocap, ferimzone, fluazinam or similar;
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28) organic tin compounds: triphenyl tin acetate, triphenyl tin chloride, triphenyl tin hydroxide or the like;
29) phosphate esters: phosphonic acid, tolclofos-methyl, fosetil or similar:
30) phthalamide-based: keyboardphthalam or similar;
31) based on benzotriazine: triazoxide or the like;
32) based on benzene sulfonamide: flusulfamide or similar:
33) pyridazinones: diclomezine or the like;
34) CAA fungicide (based on carboxylic amide): dimetomorph, flumorfe, bentiavalicarb, iprovalicarb, mandipropamide or similar:
35) tetracyclines: oxytetracycline or the like;
36) thiocarbamate-based: metasulfocarb or the like; and,
37) other compounds: etridiazole, polyoxins, oxolinic acid, hydroxyisoxazole, octinoline, siltiofam, diflumetorim, acibenzolar-s-methyl, probenazole, thiadinyl, etaboxam, ciflufenamide, proquinazide, metrafenone, fluopicolide, fluopicolide, hydroxypride, hydroxide, hydroxide, hydroxide, hydroxypride manzeb, maneb, metiram, propineb, tiuram, zineb, ziram, captano, captafol, folpet, chlorotalonil, diclofluanid, tolylfluanid, dodine, guazatin, iminoctadine acetate, iminoctadine dodecylbenzene sulfonate, anilazine, ditianamine, ditianon, ditian sodium, cinomethionate, ciprofuram, siltiofam, agrobacterium, fluorimide.
[00176] Examples of insecticides, acaricides, nematocides and soil pesticides include:
1) based on (thio) organic phosphate: such as acephate, azametiphos, azinfos-methyl, chlorpyrifos, chlorpyrifos-methyl, chlorfenvinfos, diazinon, dichlorvos, dicrotofos, dimetoate, disulfoton, etion, EPN, fenamiPetição 870170092471, 2017, p. 62/143
60/134 fos, fenitrotion, fention, isoxation, malation, metamidophos, metidation, methyl paration, mevinfos, monocrotofos, oxidemeton-methyl, paraoxon, paration, fentoate, fosalone, fosmet, fosfamidon, forato, foxim, pirimifos-methyl, profenofos, protiofos, sulprofos, tetrachlorvinfos, terbufos, triazofos, trichlorfon, fosthiazate, phosfocarb, cadusafos, disulfoton, demeton-s-methyl, BRP, CYAP, etoprofos, quinalfos, dimethilvinfos, vamidotion, or similar piraclofos;
2) carbamate-based: alanicarb, aldicarb, bendiocarb, benfuracarb, carbaryl, carbofuran, carbosulfan, phenoxicarb, phenothiocarb, metiocarb, metomyl, oxamil, pirimicarb, propoxur, tiodicarb, triazamate, etiofencarb, MIP, MT, furatiocarb, XMC or the like;
3) pyrethroid-based: alethrin, bifentrin, cyflothrin, cyhalothrin, cyphenothrin, cypermethrin, alpha-cypermethrin, betacipermethrin, zetacipermethrin, deltamethrin, sphenopherine, etofenprox, fenpropatrine, permethrin, imetrotine, pretrine, lambda, , tau-fluvalinate, teflutrin, tetramethrin, tralometrine, transflutrin, proflutrin, dimeflutrin, acrinatrine, cycloprotrine, halfenprox, flucitrinate or the like;
4) growth regulators:
a) chitin synthesis inhibitors: chlorfluazuron, diflubenzuron, flucicloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, teflubenzuron, triflumuron, bistrifluron, nobifumuron, buprofezine, diofiazine, hexamzolone, or;
b) ecdysone antagonists: halofenozide, methoxyfenozide, tebufenozide, azadiractin, chromafenozide or the like;
c) substances similar to the juvenile hormone: pyriproxifen, methoprene or phenoxycarb;
d) lipid biosynthesis inhibitors: spirodiclofen, spiromesifene, spirotetramat or similar;
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5) nicotine receptor agonist / antagonist compounds: acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpiram, thiacloprid, thiamethoxam or the like;
6) GABA antagonist compounds: acetochlor, endosulfan, etiprol, fipronil, vaniliprol, pirafluprol, pyriprol or the like;
7) macrocyclic lactone insecticides: abamectin, emamectin, milbemectin, lepimectin, spinosad, ivermectin or similar;
8) METI I compounds: phenazaquin, pyridaben, tebufenpirad, tolfenpirad, flufenirim or the like;
9) METI II and III compounds: acequinocil, fluaciprim, hydramethylnon or the like;
10) decoupling agent compounds: chlorfenapyr or the like;
11) oxidative phosphorylation inhibiting compounds: cihexitin, diafentiuron, fenbutatin oxide, propargite or similar;
12) endocrine disrupting compounds: cyromazine or the like;
13) mixed-function oxidase inhibitor compounds: piperonyl butoxide or the like;
14) sodium channel blocking compounds: indoxacarb, metaflumizone;
15) microbial pesticides: BT agents, insect pathogens, insect pathogens, nematode pathogens or the like;
16) other compounds: benclothiaz, biphenazate, cartap, flonicamid, piradalil, pimetrozine, sulfur, thiocyclam, flubendiamide, cyienopyraphene, flupirazofos, ciflumetofen, amidoflumet, bensultap, dicofol, tetradifia, pyrethimine, pyrethimine, pyrethimine, pyrethimine, , 3-dichloropropene, clofentenzine, fluacripyrim, rotenone,
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DCIP, phenisobromolate, benzomato, metaldehyde, chlorantraniliprole, espinetoram, pyrifluquinzaon or similar.
[00177] Examples of plant growth regulators include:
abscisic acid, indole butyric acid, uniconazole, eticlozate, etefon, cloxifonac, clormequat, chlorella extract, calcium peroxide, cyanamide, dichlorprop, gibberellin, daminozide, decyl alcohol, trinexapac-ethyl, mepiquat chloride, paraflutrazol chlor piperonyl butoxide, piraflufen ethyl, flurprimidol, prohydrojasmon, prohexadione-calcium, benzylaminopurine, pendimethalin, forclorfenuron, potassium hydrazide maleate, 1-naphthylacetoamide, 4-CPA, MCPB, choline, ethoxylate, ethoxylate, oxyquinate , aviglycine hydrochloride and the like.
Examples [00178] The following examples provide a more detailed explanation of the present invention by its indicated examples. However, the scope of the present invention is not limited to the following examples.
Example 1 [00179] Production of 3-endo- [2-i-butoxy-4- (trifluormethyl) phenoxy] -9- [5 (trifluormethyl) -2-pyridyloxy] -9-azabicyclo [3.3.1] nonane (Compound No. H1)
Chemical formula 13

3-endo-9-benzyl-9-azabicyclo [3.3.1] nonan-3-ol (Compound (1b)) was synthesized by the method described in WO 2007/039563.
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63/134 [00180] A solution in N, N-dimethyl formamide (14 ml) of compound (1b) (1.35 g) and 4-fluor-3-i-butoxybenzotrifluoride (compound (2b)) (1.38 g) was heated to 90 ° C, followed by the addition of 60% sodium hydride (0.35 g) and stirring for 2 hours. The resulting mixture was cooled to room temperature, poured into water and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to obtain the target compound (3b) (2.04 g).
Chemical formula 14

[00181] 10% palladium on carbon (0.4 g) was added to a solution in ethanol (20 ml) of the compound (3b) (2.04 g). The resulting suspension was heated to 50 ° C under a hydrogen atmosphere for 5 hours. The suspension was cooled and filtered over celite and the filtrate was distilled under reduced pressure. The obtained compound (4b) was used in the next reaction without further purification.
Chemical formula 15
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[00182] Tungstic acid sodium hydrate (0.13 g) was added to a solution in acetonitrile (14 ml) of the crude compound (4b) (1.41 g) at room temperature, followed by stirring for 30 minutes. The resulting mixture was cooled to 0 ° C, followed by the addition of an urea-hydrogen peroxide adduct (UHP, 0.75 g). The resulting mixture was stirred at 0 ° C for 45 minutes and further stirred at room temperature for 2 hours. Water was added to the mixture followed by extraction with chloroform. The organic layer was dried and concentrated with anhydrous potassium carbonate. The residue was purified by column chromatography to obtain compound (5b) (0.57 g). Compound (5b) was diluted with chloroform and treated with aqueous ascorbic acid to obtain a crude compound (e-1) (0.37 g). Then, tert-butoxypotassium (1M tetrahydrofuran, 1.11 ml) was added to a tetrahydrofuran solution (4 ml) of the crude compound (e-1) (0.37 g) and 2 chloro-5- (trifluoromethyl) pyridine (0.18 g) at 0 ° C under a nitrogen atmosphere, followed by heating to room temperature and stirring for 2 hours. Water was added to the resulting mixture and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography to obtain the target compound H-1 (0.27 g).
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Example 2 [00183] Production of 3-endo- [2-i-butoxy-4- (trifluoromethyl) phenoxy] -9hydroxy-9-azabicyclo [3.3.1] nonane (compound No. e-1)
Chemical formula 16
[00184] Acrylonitrile (9.07 g) was added to a solution in methanol (300 ml) of the crude compound (4b) (30.23 g) at room temperature, followed by stirring overnight. The solvent was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane: ethyl acetate = 4: 1 to 6: 4) to obtain compound (7b) (30.4 g, oil viscous).
[00185] Potassium carbonate (15.5 g) and metachloroperbenzoic acid (70% purity, 23.71 g) were added to a solution in methylene chloride (600 ml) of the compound (7b) (30.4 g) at room temperature, followed by stirring the resulting mixture for 4 hours. Anhydrous magnesium sulfate (10 g) was added to the mixture and the mixture was filtered, followed by the concentration of the solvent under reduced pressure. The residue was diluted with ethyl acetate, washed with aqueous ascorbic acid, then water, dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Hexane was added to the residue to cure and thereby obtain a crude compound (e-1) (17.79 g). In addition, the stock solution was purified by chromatography
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66/134 in column to obtain a crystalline compound (e-1) (8.12 g, melting point 112-115Ό).
Example 3 [00186] Production of 3-endo- [2-i-butoxy-4- (trifluormethyl) phenoxy] -9- [5 (trifluormethyl) -2-pyridyl thio] -9-azabicyclo [3.3.1] nonane ( compound No. N-1)
Chemical formula 17
CF,
N SH (8b)
(N-1) [00187] A methylene chloride solution (10 ml) of compound (8b) (0.55 g) that can be produced by well known methods was cooled to 0Ό under an atmosphere of nitrogen followed by the addition sulfuryl chloride (0.46 g). The resulting mixture was stirred for 1 hour, followed by concentration under reduced pressure. A solution obtained by diluting the residue with methylene chloride (10 ml) was dripped into a solution in methylene chloride (10 ml) of the crude compound (4b) (1.0 g) and triethylamine (0.34 g) with cooling with ice, followed by slow heating to room temperature and stirring overnight. The resulting mixture was poured into water, followed by extraction with chloroform. The organic layer was washed with water, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane: ethyl acetate = 9: 1) to obtain the target compound (N-1) (1.36 g, viscous oil).
Example 4 [00188] Production of 3-oxa-7-endo- [5- (trifluormethyl) -2-pyridyloxy] -9- [2Petition 870170092471, of 11/29/2017, p. 69/143
67/134 isopropoxycarbonyl-4- (trifluormethyl) phenoxy] -9-azabicyclo [3.3.1] nonane (compound No. (K-12))
Chemical formula 18
NaBH4

[00189] 9-benzyl-3-oxa-9-azabicyclo [3.3.1] nonan-7-one (1c) was synthesized by the method described in W02007 / 022502. Boron sodium hydride (0.785 g) was added to a solution in ethanol (50 ml) of compound (1c) (4 g) at room temperature, followed by stirring the resulting mixture for 3 hours. The mixture was cooled and concentrated under reduced pressure, followed by dripping in water and extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to obtain compound (2c) (3.62 g).
Chemical formula 19 'Ό ,, ΛΧ (2c) (3c)
N ll
[00190] A DMF solution (30 ml) of compound (2c) (2.45 g) and 2-chloro-5- (trifluoromethyl) pyridine (2.86 g) was heated to 80 °, followed by the addition of 60% sodium (0.42 g) to the solution. The resulting mixture was stirred for 30 minutes, followed by the addition of 60% sodium hydride (0.42 g). The resulting mixture was stirred for an additional 2 hours. Then, the resulting mixture was cooled to room temperature, poured into water, followed by extraction with ethyl acetate. THE
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68/134 organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to obtain compound (4c) (3.05 g)
Chemical formula 20
[00191] 20% palladium hydroxide on carbon (0.92 g) was added to a solution in ethanol (50 ml) of compound (4c) (3.05 g), followed by heating the resulting suspension at 50Ό for 6 hours . The resulting mixture was cooled and filtered over celite, and the filtrate was distilled under reduced pressure. The obtained compound (5c) was used in the next reaction without further purification.
Chemical formula 21
(5c)
[00192] Acrylonitrile (1.06 g) was added to a solution in methanol (50 ml) of the crude compound (5c) (2.3 g) at room temperature, followed by stirring overnight. The solvent was concentrated under reduced pressure and the residue was purified by silica gel column chromatography to obtain compound (6c) (2.11 g).
[00193] Compound (6c): melting point 87-90Ό
H-NMR (CDCl3, δppm) 8.41 (s, 1H), 7.73 (d, 1H), 6.81 (d,
1H), 5.47-5.40 (m, 1H), 3.87 (d, 2H), 3.60 (d, 2H), 2.98 (t, 2H), 2.84 (d, 2H) ), 2.50-2.42 (m, 4H), 1.87 (d, 1H), 1.82 (d, 1H)
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Chemical formula 22
(oc) (8c) (7c) [00194] Meta-chloroperbenzoic acid (70% purity, 0.58 g) and potassium carbonate (0.4 g) were added to a solution in methylene chloride (20 ml) of compound (6c) (0.76 g) at room temperature, followed by stirring for one hour. Anhydrous magnesium sulfate was added to the mixture and the mixture was filtered over celite, followed by the concentration of the solvent under reduced pressure. The residue was purified by column chromatography to obtain compound (7c) (0.38) and compound (8c) (0.2 g).
[00195] Compound (8c): melting point 110-113Ό
1H-NMR (CDCI3, oppm, measuring temperature 21.2Ό)
8.43 (s, 1H), 7.73 (d, 1H), 6.80 (d, 1H), 5.68-5.61 (m, 0.7H), 5.39-5.36 ( m, 0.3H), 4.38 (d, 0.5H), 3.79 (s, 3H), 3.37 (d, 0.5H), 3.24 (d, 1.5H), 3 , 11 (d, 0.5H), 2.75-2.53 (m, 2H), 2.17-2.05 (brd, 0.5H), 1.78-1.72 (d, d, 1.5H)
Chemical formula 23
(7c) (K-12) [00196] 1,2-diphenyl hydrazine (0.14 g) was added to a THF solution (5 ml) of compound (7c) (0.38 g) at room temperature, followed by by stirring the resulting mixture for 30 minutes. A 60% sodium hydride solution (0.06 g) was added to the mixture followed by stirring for 10 minutes. Then, a THF solution (5 ml) of
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70/134 Isopropyl 2-fluoro-5- (trifluormethyl) benzoic acid (0.314 g) was added to the resulting mixture, followed by stirring for one hour. The mixture was poured into water, and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to obtain the target compound (compound No. (K12)) (0.27 g, viscous oil).
Example 5 [00197] Production of 3-endo- [2-butoxy-4- (trifluormethyl) phenoxy] -9- [5 (trifluormethyl) -2-pyridyloxy] -9-azabicyclo [3.3.1] nonane (compound No. (H54))
chemical formula
(9) (10)
[00198] 60% sodium hydride (0.75 g) was added to a DMF solution (20 ml) of 2-fluorine-5- (trifluoromethyl) phenol (2.83 g) with ice cooling. The resulting mixture was stirred at room temperature for 30 minutes, and methyl chlorine ether (1.39 g) was dripped into the mixture with ice cooling. The mixture was then warmed to room temperature and stirred for 30 minutes, and then heated to 80Ό and stirred for another hour. Compound (10) (4 g) and 60% sodium hydride (0.94 g) were added to the resulting mixture, followed by stirring for 3 hours. The mixture was then cooled to room temperature, poured into water and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to obtain the target compound (11)
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71/134 (6.29 g).
Chemical formula 25

(12) [00199] 20% palladium hydroxide on carbon (1.25 g) was added to a solution in ethanol (100 ml) of compound (11) (6.27 g). The resulting suspension was heated to 50Ό under a hydrogen atmosphere for 2 hours, followed by stirring at room temperature for one night. The mixture was then filtered over celite and the filtrate was distilled off under reduced pressure. The obtained compound (12) was used in the next reaction without further purification.
Chemical formula 26
[00200] Acrylonitrile (1.45 g) was added to a solution in methanol (50 ml) of crude compound (12) (4.71 g) at room temperature, followed by stirring overnight. The solvent was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain compound (13) (5.09 g, viscous oil).
Chemical formula 27
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(13) tZ '
K2CO [00201] Meta-chloroperbenzoic acid (70% purity, 1.2 g) and potassium carbonate (0.78 g) were added to a solution in methylene chloride (30 ml) of compound (13) (1, 5 g) at room temperature followed by stirring the resulting mixture for 2 hours. Anhydrous magnesium sulfate (10 g) was added to the mixture and the mixture was filtered, followed by the concentration of the solvent under reduced pressure. The residue was diluted with methylene chloride, washed with aqueous ascorbic acid, then with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to obtain compound (e-14) (1.35 g).
Chemical formula 28

[00202] t-butoxypotassium (1M THF, 3.6 ml) was added to a THF solution (20 ml) of compound (e-14) (1.3 g) and 2-chloro-5 (trifluoromethyl) pyridine (0 , 65 g) at 0Ό under a nitrogen atmosphere, followed by heating to room temperature with stirring for 2 hours. The resulting mixture was then poured into water and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to obtain compound (H-51) (0.67g, viscous oil).
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Chemical formula 29

[00203] Bromine trimethyl silane (0.302 g) was added slowly to a solution in methylene chloride (5 ml) of compound (H-51) (0.25 g) under an atmosphere of nitrogen at -30Ό. The resulting mixture was then stirred at -30 ° for one hour, followed by 2 hours to warm to 0 °. The mixture was then poured into ice water, followed by extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to obtain compound (H-53) (0.13g, melting point 141-144X3).
Chemical formula 30

cf ₃ nBul
(H-54) [00204] t-Butoxypotassium (0.085 g) was added to a solution in THF (6 ml) of compound (H-53) (0.35 g) and 1-iodobutane (0.14 g) with cooling with ice. Then, the mixture was warmed to room temperature, and further heated to 50 ° and stirred overnight. The resulting mixture was then cooled to room temperature, poured into water, and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to obtain the target compound (compound
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No. (H-54)) (0.24 g, viscous oil).
Example 6 [00205] Production of 3-endo- [2-phenyl-4- (trifluormethyl) phenoxy] -9- [5 (trifIuormethyl) -2-pyridyloxy] -9-azabicyclo [3.3.1] nonane (compound No. (H85))
Chemical formula 31
[00206] Anhydrous trifluoromethane sulfonic acid (3.66 g) was added slowly to a solution in methylene chloride (50 ml) of compound (H-53) (5 g) and pyridine (2.14 g) with ice cooling . Then, the mixture was warmed to room temperature and stirred overnight. The resulting mixture was then poured into ice water and extracted with methylene chloride. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to obtain compound (H-84) (3.7 g, m.p. 127-130 °).
Chemical formula 32

(H-85) [00207] Water (2 ml), cesium carbonate (0.88 g), phenyl boronic acid (0.098 g) and tetracis (triphenyl phosphine) palladium (0) (0.078 g) were added to a solution in THF (4 ml) of the compound (H-84) (0.4 g) under a nitrogen atmosphere. The resulting mixture was then heated to
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80 ° C and stirred overnight. The mixture was cooled to room temperature, poured into water and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to obtain the target compound (compound No. (H-85)) (0.2 g, viscous oil).
[00208] The cyclic amine compounds of the present invention, which can be produced by the production methods described above, are shown in TABLES 1 to 5.
[00209] Additionally, (R ¹⁰ ) m, (R ¹¹ ) n, A, (R ²¹ ) r, and Cy ² - (R ²⁰ ) p in TABLE 1 represent the substituents of the cyclic amine compound represented by the formula (Ig ).
[00210] (R ¹⁰ ) m, (R ¹¹ ) n, A, (R ²¹ ) r, and Cy ² - (R ²⁰ ) p in TABLE 2 represent the substituents of the cyclic amine compound represented by the formula (Ih).
[00211] (R ¹⁰ ) m, (R ¹¹ ) n, A, (R ²¹ ) r, Cy ¹ , Cy ² , and (R ²⁰ ) p in TABLE 3 represent the substituents of the cyclic amine compound represented by the formula ( Ii).
[00212] (R ¹⁰ ) m, (R ¹¹ ) n, A, (R ²¹ ) r, Cy ¹ , Cy ² , and (R ²⁰ ) p in TABLE 4 represent the substituents of the cyclic amine compound represented by the formula ( Ij).
[00213] (R ¹⁰ ) m, (R ¹¹ ) n, A, (R ²¹ ) r, Cy ¹ , Cy ² , and (R ²⁰ ) p in TABLE 5 represent the substituents of the cyclic amine compound represented by the formula ( Ik).
[00214] (R ¹⁰ ) m, (R ¹¹ ) n, A, (R ²¹ ) r, Cy ¹ , Cy ² , and (R ²⁰ ) p in TABLE 6 represent the substituents of the cyclic amine compound represented by the formula ( Il).
[00215] Additionally, in TABLES 1-6, the numerical values shown in front of the substituents represent the places of substitution. Additionally, Et represents an ethyl group, Me represents
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76/134 methyl group, ⁿ Bu represents n-butyl group, 'Bu represents sibutyl group, ^s Bu represents s-butyl group, ^l Bu represents t-butyl group, ⁿ Pen represents n-pentyl group, ⁿ Hex represents n- group hexyl, ^c Pr represents cyclopropyl group, ^c Bu represents cyclobutyl group, ^c Pen represents cyclopentyl group, ^c Hex represents cyclohexyl group.
Chemical formula 33
Ç (R) _n
V ¹ <ύ ^Ν · ₂ / ^r2 ° 'p ⁰ (R ²¹ ) _r (fe)
[Table 11] TABE LA 1 At the. A'A, aa THE CyMUA IR ² '/ i-i-l 2-ÍOC-l / Pr) 4-C-3 UA 5-0 F ₃ - pyridin -2- il - H-2 2-ÍOCH / Pri 4-C = j UA 5-CF3-pyridin -2-yl - H-3 2-ÍCH ₂ OCHÍOCH ₃ ) CH ₃ ) 4-C = ₃ C _to H _t 5-0 F ₃ - pyridin -2- il - H-4 Z-ICsCHs) 4-C- ₃ UA 5-0F ₃ - pyridin -2- il - H-5 2-ÍOCH / Pr) 4-C = j UA 5-CF3-pyridazin -3- yl - H-6 2-ÍOCH / Pr) 4-C = ₃ C _to H _t 5-CF3-pyridazin -3- j | - H-7 2-; CH ₂ OCH (OCH: i) CI-I: i) 4-C- ₃ UA 6-0 F3- pyridazin -3- il - H-8 2-; CO ₂ 'Pr) 4-0 = 3 UA 6-0 F3-pyridazin -3- i | - H-9 2-ÍOCH / Pr) 4-C = ₃ UA 5-CF3-pyrimidin-2-yl - H-1D 2-ÍOC-l / Pr) 4-C = ₃ UA 5-0 F3- pyrimidin-2-yl - H-11 2-; θΗ ₂ ΟΟΗίΟΟΗ3) ΟΗ3) 4-0 = 3 UA 5-0 F3- pyrimidin-2-yl - H-12 2-ÍCOj'Pr) 4-C = ₃ UA 5-C F3- pyrimidin-2-yl - H-13 2-ÍOCH / Pr) 4-C = ₃ UA 5-CF3- thiazol-2-yl - H-14 2-ÍOCH / Pri 4-0 = 3 UA 5-CF3- thiazol-2-yl - H-15 2 — IC ^ OCHÍOCHjJCHj) 4-C ^ UA 5-CF3- thiazol-2-yl - H-16 2- {εθ ₂ ^! ΡιΟ 4-0 = 3 UA 5-CF ₃ - thiazol-2-yl - H-17 2-ÍOCH / Pr) 4-0 = 3 UA 5-CF ₃ - [1.3,4] thiadiazol-2-yl - H-18 2-ÍOCH / Pr) 4-0 = 3 UA 5-CF ₃ - 3 4]. thiadiazol-2-il - H-19 2-; C- ₂ OCH (OCH3) C-13) 4-0 = 3 UA 5-CF ₃ - [1,3,4} thiadiazol-2-yl - H-2D 2-ÍCO / Pr) 4-0 = 3 UA 5-CF3-[1,3,4} thiadiazol-2-yl - H-21 2-ÍOCH / Pr) 4-0 = 3 ch ₂ och ₂ 5-CF3-pyridin -2-yl - H-22 2-ÍOC-l / Pr) 4-0 = 3 CH ₂ OC-i ₂ 5-CF3-pyridin -2-yl - H-23 2-ÍCH ₂ OCHÍOCH ₃ ) CH ₃ ) 4-0 = 3 ch ₂ och ₂ 5-0 F3-pyridin -2-il - H-24 2-; CO ₂ 'Pr) 4-0 = 3 ch ₂ och ₂ 5-CF3-pyridin -2-yl - H-25 2-ÍOCH / Pr) 4-0 = 3 CH ₂ OC-i ₂ 6-CF3-pyridazin -3- yl -
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77/134 [Table 2] TABLE 1 (Continued)
At the. THE -1-26 2-ÍOC'H / Pr) 4-CF, C4 ₂ OC4 ₂ δ-CF, - pyridazin -3- il - -1-27 2-; CH ₃ OC4 (OC4j) CHj) 4-CF, C4 ₃ OC4 _; 6-CF, - pyridazin -3- il - 4-28 2-'CO / Pr) 4-CFj C4 ₃ OC4j 6-CF, - pirdazin -3- il - 4-29 2- (OC4 ₃ Pr) 4-CFj C4 ₃ OC4 ₃ 5-CF, - pyrimidin-2-yl - -1-30 2- (OC V Pr) 4-CF, C4 ₃ OC4j 5-CF _s - pyrimidin-2-yl - 4-31 2-; C4 ₂ OC4COCHj) C4jj 4-CF, C4 ₂ OC4 ₃ 5-CF, - pyrimidin-2-yl - -1-32 2- (CO ₃ 'Pr) 4-CF, C4 ₃ OC4í 5-CF _s - pyrimidin-2-yl - -1-33 2- (OC4 _s Pr) 4-CF, C4 ₂ OC4 ₃ 5-CI-3-thiazol-2-yl - 4-34 2-IOCH; 'Pr) 4-CFj C4 ₃ OC4í 5-CF3- thiazole-241 - -1-35 2- (04,004 (004,) 04,) 4-CF, C4 ₃ OC4 ₃ 5-CF, - thiazol-2-yl - -1-36 2-; οο; ργ) 4-CFs C4 ₃ OC4í 5-CF ₃ - liazol-2-yl - -1-37 2- (OC4 ₃ Pr) 4-CF, C4jOC4 ₃ Õ-CF3-[1,3,4] thiadia20l-2-yl - -1-38 2- (004 / Pr) 4-CF, C4 ₃ OC4 ₃ 5 ^_ CFa ^- [1Λ4ί thiadiazol-2-il - -1-39 2- (C4 ₃ OC4 (OC4 ^ C4,) 4-CF, C4 ₃ OC4 ₃ 5-CFj-[l, 3.4] thiadiazole-241 - -1-40 2-CCOj'Pr) 4-CF, C4 ₃ OC4j õ-CF ₃ - [1.3.4] tiadi3201-241 - - 41 2- (004, Pr) 4-CF, 5-C -pyridin -2-yl - -1-42 Z-COEO 4-CF, C, 4 _S S-CFj-pyridin -2-yl - 4-43 2-ÍOPr) 4-CF, C, H ₆ 5-CF ₃ -pjndi _n * 2- il - 4-44 2- (OC4 / Pr) 4-CF, C, 4 _s 5-C -pyridin -2-yl - 4-45 2-CH ₃ OCHCOCHj) CH3) 4-CF, C _s H ₆ 5-C N-pyridin -2-yl - 4-46 2- (CO ₃ 'Pr) 4-CF, 5-C -pyridin -2-yl - 4-47 2- (OC4 ₂ Pr) 4-CF, 6-C -piridaiin -3- yl - 4-48 2-COC4 / Pr) 4-CF, C, H ₆ 5-C -pyrid In -3- il - 4-49 2- (042004 (004,) 045) 4-CF, c, h ₅ 5-C -pÍNda2in -3 * il - 4-50 2 - ,; COjPr) 4-CF, C ₃ H _s S-C -pinda2Ín -3- il -
Petition 870170092471, of 11/29/2017, p. 80/143
78/134
Table 3] TABLE 1 (Continued]
At the. Λ THE H-51 2-tOCHiOWe) 4-CFa C3-I6 5 — CF3- pyridin -2-yl - H-52 Z- (OCHo’Pr) 4-CF _s Cshe S-CN-pitidazin -3- il - H-53 2-0 H 4-CF ₅ CaMe 5-CF3- pyridiri -2- íl - H-54 2-; oblü 4-CF ₃ C ₃ Hb 5-CF3- pyridine ~ 2 il - H-55 2 - ([l.3] Dioxolarr-2-yl) 4-CF _q CjHt 5-CF ₃ - pyridin -2- il - H-55 i-ico-joA; 4-CFj C3H6 5-CF ₃ - pyridir -2- il - H-57 2-ICH3OCH3) 4 CF ₃ CíHg 5-CF3- pyridir -2-yl - H-58 2- (CH ₄ OEt) 4-CF _a C ₃ H6 5-CF ₃ - pyridin -2- il - H-58 2-ÍNH'Bu) 4-CF3 C ₃ H6 5-CF ₃ - pyridin -2- il - H-ÔO 2- (0 ¹ Pr) 4-CFj C ₃ H, í 5-CF3- pyridir -2-yl - H-51 2-ium ^s Bu) 4-CF3 C ₃ H6 5 — CF ₃ - pyridine -2- j | - H-57 2- (OCO _s ' Pr) 4-CF3 Cjhe 5-CF3- pyridir -2-yl - H-53 Z-; OCH ₄ CF ₃ ) 4-CF ₃ C ₃ H6 5-CF3- pyridir -2-yl - H-54 2-COCH, C- ^ CH ₂ ) 4-CF ₃ C ₃ Hb 5-CF ₃ - pyridir -2- il - H-55 2- (OC-hCH = C (CHji) 4-CF3 C ₃ H6 5-CF ₃ -pyridin -2-yl - H-55 2-COCh / B'J) 4-CG C ₃ Hg 5-CF3- pyridir -2-yl - H-57 2- (OCHjCH = CCI ₄ ) 4-CFj C ₃ H5 5-CF3-pyridir -2-yl - H-53 2-IOCH-jC = CH) 4-CF _a C ₃ -fe 5-CF3-pyridin -2-yl - H-58 2- (OC-b «CH, 3 = CH ₂ > 4-CF3 C ₃ Hb 5-CF3-pyridin -2-yl - H-70 2-IOCHi’B'j) 4-CF _a C ₃ H6 5-GF3- pyridir -2-yl - H-71 2- (OCHjCN) 4-CF3 C ₃ Hg 5-CF ₃ - pyridir -2- il - H-72 2-rocHCCH, x) CH3) 4-CFj C ₃ Hs 5-CF3-pyridin -2-yl - H-73 2-ÍCO, ’Pr) 4-CF _a Cj-ΐ 5-CF3-pyridin -2-yl - H-74 2-ÍCOjEt) 4-CF ₃ CsHs 5-CF3- pyridir -2-yl - H-75 2- (OCH ₂ 'pr) 4-CF, 5-GF3-6-CI-pyridin -2-yl -
JTabela4] ^^^^^^^^^^ TABLE J CDTTtnua £ ãD2 _i
At the. Λ THE CyNB ^ p (r ²¹ ; H-76 2-iOC-j'Pr) 4-CF ₃ CjH; 3-CF3-6-CI-pyridin -2-yl - H-77 2- (0Here 4-CFj CjH ₅ 5-CF, - pyridir -2- il - H-78 2-IOCH _z [2,2-CI ia-Pti-Tr]) 4-CFj CjHj 5-CF, -pyridin -2-yl - H-79 2 - 0 C “2 Ac} 4-0 ^ 3 CjH, 5-CFj-pyridin -2-yl - H-00 2-COCH ₅ CH (OH) GH3) 4-CFj CjH ₅ 5-CFj-pyridin -2-yl - H-81 Z-ÍOCHjCHÍOCHjXJHj) 4-CFj CjH; 5-CFj-pyridin -2-yl - H-82 2-ÍO‘Pen) 4-CF _s CjHí 5-CF _} -pyridin -2- il - H-83 2 ^- (OCONH'Pr) 4-C ^ C3H3 5-CFj- pyridir -2-yl - H-84 2- (0 SOjC-j) 4-CFj c ₃ h _s 5-CFj-pyridin -2-yl - H-85 2-Ph 4-CFj CjHj 5-CF, - pyridir -2- il - H-96 2-pmdtn -3- jl) 4-CF ₃ CjH, 5-CFj- pyridir -2-yl - H-87 2- {Y ⁿ Prt 4-CFj HERE 5-CFj-pyridin -2-yl - H-83 2- (CH _i CH = CHj5 4-CFj CjH _{ 5-CF, -pyridin -2-yl - H-89 2-CO ^r Pr) 4-CI CjHj 5-CFj-pyridin -2-yl - H-90 2- (OPr) 4-CFj CjHj 5-CFj- pyridir -2-yl - H-91 2- (OC- ₂ 'Pr) 4-CI CHjOCHj 5-CFj-pyridin -2-yl -
Petition 870170092471, of 11/29/2017, p. 81/143
79/134 [Table 5]
TABLE 1 (Continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE Cy2- (R ²⁰ ) p (R ²¹ ) r H-92 2- (OCH3), 3- ⁿ Pr 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-93 2- (OCH (CH3) CH2) -3 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-94 2- ⁿ Bu 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-95 2-Pen 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-96 2- (CH2CH2CeCH) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-97 2- (CH = N-OH) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-98 2- (CH = N-OCH3) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-99 2- (CO ⁱ Pr) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-100 2- (OCH2OAc) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-101 2- (OCH2CH (O CH3) 2) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-102 2- (OCH2CH2SO2CH3) 4-CF3 C3H6 5-CF3-pyridin-2-yl H-103 2- (OCH2Ph) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-104 2- (OCH2- (pindin-3-yl)) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-105 2- (OCH2-tetrahydrofuran-2-il]) 4-CF3 C3H6 5-CF3-pyridin-2-yl H-106 2- (OCH2CO2CH3) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-107 2- (OCH2CON (CH3) 2) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-108 2- (OC2H4NO2) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-109 2- (OC2H4Si (CH3) 3) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-110 2- (SCH2CH = CH2) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-111 2- (SCH2CeCH) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-112 2- (SO2CH3) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl
Petition 870170092471, of 11/29/2017, p. 82/143
80/134 [Table 6]
TABLE 1 (Continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE Cy2- (R ²⁰ ) p (R ²¹ ) r H-113 2- (SO ₂ CH ₂ CH = CH ₂ ) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-114 2- (OPh) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-115 2- (O- (pyridine-3-il)) 4-CF3 C3H6 5-CF3-pyridin-2-yl H-116 2-NH2 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-117 2- (N (CH3) ⁱ Pr) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-118 2- (NHCH ₂ CH = CH ₂ ) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-119 2- (NHCH2CECH) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-120 2- (NHAc) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-121 2- (NHSO2CH3) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-122 2- (NHSO ₂ Ph) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-123 2- (CONH ₂ ) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-124 2- (O-N = C (CH3) 2) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-125 2- (SPh) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-126 2- (S- (pyridin-3-yl)) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-127 2- (CS'Pr) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-128 2- (CO (S ⁱ Pr)) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-129 2- (CS (O ⁱ Pr)) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-130 2- (CS ₂ ⁱ Pr) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-131 2- (Si (CH3) 3) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-132 2-NO2 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-133 2- (OCH ₂ CH ₂ ) -3 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-134 2- (OCH ₂ CH ₂ O) -3 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-135 2- (OCH ₂ O) -3 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-136 24CH2OCH2CF3) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-137 24CH2OCH2CN) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl
Petition 870170092471, of 11/29/2017, p. 83/143
81/134 [Table 7]
TABLE 1 (continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE Cy2- (R ²⁰ ) p (R ²¹ ) r H-138 24CH2OCH2OCH3) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-139 2- (CH2OCH2OCPen) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-140 2- (CH2OCH2Ac) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-141 2- (CH2OCH2CH (OCH3) 2) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-142 24CH2OCH2SO2CH3) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-143 2- (CH2OCH2Ph) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-144 2- (CH2OCH2- (pyridine-3-yl)) 4-CF3 C3H6 5-CF3-pyridin-2-yl H-145 2- (CH2OCH2- [tetrahydrofuran-2-l]) 4-CF3 C3H6 5-CF3-pyridin-2-yl H-146 2- (CH2SCH2CF3) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-147 2- (CH2SCH2CN) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-148 2- (CH2SCH3) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-149 2- (CH2SCH2O ^C Pen) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-150 2- (CH2SCH2Ac) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-151 2- (CH2SCH2Ph) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-152 2- (CH2SCH2- (pyridin-3-yl)) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl H-153 2- (CH2SCH2-[tetrahydrofuran-2-il]) 4-CF3 C3H6 5-CF3-pyridin-2-yl
[Table 8]
TABLE 1 (Continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE Cy2- (R ²⁰ ) p (R ²¹ ) r H-154 2- (CO2CH2[tetrahydrofuran-2-yl]) 4-CF3 C3H6 5-CF3-pyridin-2-yl H-155 2- (Spiro [2.2] pent-1-yl) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl
Petition 870170092471, of 11/29/2017, p. 84/143
82/134
TABLE 1 (Continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE Cy2- (R ²⁰ ) p (R ²¹ ) r H-156 2- (1-CH ₃ -spiro [2.2] pent-1-yl) 4-CF3 C3H ₆ 5-CF ₃ -pyridin-2-yl H-157 2- (1-HOCH ₂ -piro [2.2] pent-1-yl) 4-CF3 C3H ₆ 5-CF ₃ -pyridin-2-yl H-158 2- (Spiro [2.2] pent-1-yloxy) 4-CF3 C3H ₆ 5-CF ₃ -pyridin-2-yl H-159 2- (Spiro [2.2] pent-1-ylmethoxy) 4-CF3 C3H ₆ 5-CF ₃ -pyridin-2-yl H-160 2- (2- ^c Pr- ^c Pr) 4-CF3 C3H ₆ 5-CF ₃ -pyridin-2-yl H-161 2- (2- ^c Pr- ^c PrO) 4-CF3 C3H ₆ 5-CF ₃ -pyridin-2-yl H-162 2- (OCH2 ⁱ Pr) 4-CF3 C3H ₆ 5-SF ₅ -pyridin-2-ylH-163 2- (OCH2 ^C Pr) 4-CF3 C3H ₆ 5-SF ₅ -pyridin-2-yl H-164 2- (CH2OCH (OCH3) CH3) 4-CF3 C3H ₆ 5-SF ₅ -pyridin-2-yl H-165 2- (CO2 ⁱ Pr) 4-CF3 C3H ₆ 5-SF ₅ -pyridin-2-yl H-166 2- (O ⁿ Pr) 4-CF3 C3H ₆ 5-SF ₅ -pyridin-2-yl H-167 2- (OCH2 ⁱ Pr) 4-CF3 C3H ₆ 5-SF ₅ -pyridin-2-yl H-168 2- (OCH2 ^C Pr) 4-CF3 C3H ₆ 5-SF ₅ -pyridin-2-yl H-169 2- (CH2OCH (OCH3) CH3) 4-CF3 C3H ₆ 5-SF ₅ -pyridin-2-yl
[Table 9]
TABLE 1 (Continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE Cy2- (R ²⁰ ) p (R ²¹ ) r H-170 2- (CO2 ⁱ Pr) 4-CF3 C3H ₆ 5-SF ₅ -pyridin-2-yl H-171 2- (O ⁿ Pr) 4-CF3 C3H ₆ 5-SF ₅ -pyridin-2-yl H-172 2- (OCH2 ⁱ Pr) 4-SF5 C3H ₆ 5-SF ₅ -pyridin-2-yl H-173 2- (OCH2 ^C Pr) 4-SF5 C3H ₆ 5-SF ₅ -pyridin-2-yl H-174 2- (CH ₂ OCH (OCH3) CH3) 4-SF5 C3H ₆ 5-SF ₅ -pyridin-2-yl H-175 2- (CO2 ⁱ Pr) 4-SF5 C3H ₆ 5-SF ₅ -pyridin-2-yl H-176 2- (O ⁿ Pr) 4-SF5 C3H ₆ 5-SF ₅ -pyridin-2-yl H-177 2- (OCH2 ⁱ Pr) 4-SF5 C3H ₆ 5-SF ₅ -pyridin-2-yl H-178 2- (OCH2 ^C Pr) 4-SF5 C3H ₆ 5-SF ₅ -pyridin-2-yl H-179 2- (CH ₂ OCH (OCH3) CH3) 4-SF5 C3H ₆ 5-SF5-pyridin-2-yl
Petition 870170092471, of 11/29/2017, p. 85/143
83/134
TABLE 1 (Continued) H-180 2- (CO2 ⁱ Pr) 4-SF5 C3H6 5-SF ₅ -pyridin-2-yl H-181 2- (O ⁿ Pr) 4-SF5 C3H6 5-SF ₅ -pyridin-2-yl H-182 2- (OCH2'Pr) 4-CN C3H6 5-CF ₃ -pyridin-2-yl H-183 2- (OCH2 ^C Pr) 4-CN C3H6 5-CF ₃ -pyridin-2-yl H-184 2- (CH2OCH (OCH3) CH3) 4-CN C3H6 5-CF ₃ -pyridin-2-yl H-185 2- (CO2 ⁱ Pr) 4-CN C3H6 5-CF ₃ -pyridin-2-yl H-186 2- (O ⁿ Pr) 4-CN C3H6 5-CF ₃ -pyridin-2-yl H-187 2- (OCH ^ Pr) 4-CF3 C3H6 5-Cl-pyridin-2-yl H-188 2- (OCH2 ^C Pr) 4-CF3 C3H6 5-Cl-pyridin-2-yl H-189 2- (CH2OCH (OCH3) CH3) 4-CF3 C3H6 5-Cl-pyridin-2-yl H-190 2- (CO2 ⁱ Pr) 4-CF3 C3H6 5-Cl-pyridin-2-yl
[Table 10]
TABLE 1 (continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE Cy2- (R ²⁰ ) p (R ²¹ ) r H-191 2- (O ⁿ Pr) 4-CF3 C3H6 5-Cl-pyridin-2-yl H-192 2- ⁿ Bu 4-Br C3H6 5-CF ₃ -pyridin-2-i H-193 2- (CH2CH = CH2) 4-Br C3H6 5-CF ₃ -pyridin-2-i H-194 2- (CH2O ⁱ Pr) 4-Br C3H6 5-CF ₃ -pyridin-2-i H-195 2- (CH2OEt) 4-Br C3H6 5-CF ₃ -pyridin-2-i H-196 2- (OEt) 4-Br C3H6 5-CF ₃ -pyridin-2-i H-197 2- (O ⁿ Pr) 4-Br C3H6 5-CF ₃ -pyridin-2-i H-198 2- (O ⁱ Pr) 4-Br C3H6 5-CF ₃ -pyridin-2-i H-199 2- (O ⁿ Bu) 4-Br C3H6 5-CF ₃ -pyridin-2-i H-200 2- (O ^s Bu) 4-Br C3H6 5-CF ₃ -pyridin-2-i H-201 2- (OCH2 ^S Bu) 4-Br C3H6 5-CF ₃ -pyridin-2-i H-202 2- (OCH2 ^t Bu) 4-Br C3H6 5-CF ₃ -pyridin-2-i H-203 24OCH2CF3) 4-Br C3H6 5-CF ₃ -pyridin-2-i H-204 2- (OCH2CN) 4-Br C3H6 5-CF ₃ -pyridin-2-i H-205 2- (OCH2CH (OH) CH3) 4-Br C3H6 5-CF ₃ -pyridin-2-i H-206 2- (OCH2CH (OCH3) CH3) 4-Br C3H6 5-CF ₃ -pyridin-2-i
Petition 870170092471, of 11/29/2017, p. 86/143
84/134
TABLE 1 (continued) H-207 24OCH2OCH3) 4-Br C3H6 5-CF ₃ -pyridin-2-yl H-208 2- (OCH (CH3) OCH3) 4-Br C3H6 5-CF ₃ -pyridin-2-yl H-209 2- (OCH _: Ac) 4-Br C3H6 5-CF ₃ -pyridin-2-yl H-210 2- (OCH ₂ CH = CH ₂ ) 4-Br C3H6 5-CF ₃ -pyridin-2-yl H-211 2- (OCH ₂ CH = C (CH3) 2) 4-Br C3H6 5-CF ₃ -pyridin-2-yl H-212 2- (OCH2CECH) 4-Br C3H6 5-CF ₃ -pyridin-2-yl
[Table 11]
TABLE 1 (Continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE Cy2- (R ²⁰ ) p (R ²¹ ) r H-213 2- (OAc) 4-Br C3H6 5-CF ₃ -pyridin-2-yl H-214 2- (OCO2'Pr) 4-Br C3H6 5-CF ₃ -pyridin-2-yl H-215 2- (OCONH Pr) 4-Br C3H6 5-CF ₃ -pyridin-2-yl H-216 24OSO2CF3) 4-Br C3H6 5-CF ₃ -pyridin-2-yl H-217 2- (NHCH2'Pr) 4-Br C3H6 5-CF ₃ -pyridin-2-yl H-218 2- (CO2Et) 4-Br C3H6 5-CF ₃ -pyridin-2-yl H-219 2- (Y ⁿ Pr) 4-Br C3H6 5-CF ₃ -pyridin-2-yl H-220 2 - ([1,3] dioxolan-2-yl) 4-Br C3H6 5-CF ₃ -pyridin-2-yl H-221 2- (OCH2'Pr) 4-CH (CF3) 2 C3H6 5-CF ₃ -pyridin-2-yl H-222 2- (OCH2 ^c Pr) 4-CH (CF3) 2 C3H6 5-CF ₃ -pyridin-2-yl H-223 2- (CH ₂ OCH (OCH3) CH3) 4-CF (CF3) 2 C3H6 5-CF3-pyridin-2-yl H-224 2- (CO ₂ Pr) 4-CF (CF3) 2 C3H6 5-CF ₃ -pyridin-2-yl H-225 2- (O ⁿ Pr) 4-C (CF3) 2OCH3 C3H6 5-CF ₃ -pyridin-2-yl H-226 2- ⁿ Bu 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-yl H-227 2- (CH ₂ CH = CH ₂ ) 4-CF3 CH ₂ N (CH3) CH ₂ 5-CF ₃ -pyridin-2-yl H-228 2- (CH ₂ OPr) 4-CF3 CH ₂ N (CH3) CH ₂ 5-CF ₃ -pyridin-2-yl H-229 2- (CH ₂ OEt) 4-CF3 CH ₂ N (CH3) CH ₂ 5-CF ₃ -pyridin-2-yl H-230 2- (OEt) 4-CF3 CH ₂ N (CH3) CH ₂ 5-CF ₃ -pyridin-2-yl H-231 2- (O ⁿ Pr) 4-CF3 CH ₂ N (CH3) CH ₂ 5-CF ₃ -pyridin-2-yl H-232 2- (OPr) 4-CF3 CH ₂ N (CH3) CH ₂ 5-CF ₃ -pyridin-2-yl
Petition 870170092471, of 11/29/2017, p. 87/143
85/134
TABLE 1 (Continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE Cy2- (R ²⁰ ) p (R ²¹ ) r H-233 2- (O ⁿ Bu) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-yl H-234 2- (O ^s Bu) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-yl H-235 2- (OCH / Pr) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-yl
Table 12
TABLE 1 (Continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE Cy2- (R ²⁰ ) p (R ²¹ ) r H-236 2- (OCH2 ^C Pr) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-i H-237 2- (OCH2 ^S Bu) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-i H-238 2- (OCH2 ^t Bu) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-i H-239 24OCH2CF3) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-i H-240 2- (OCH2CN) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-i H-241 2- (OCH2CH (OH) CH3) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-i H-242 2- (OCH2CH (OCH3) CH3) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-i H-243 24OCH2OCH3) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-i H-244 2- (OCH (CH3) OCH3) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-i H-245 2- (OCH2Ac) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-i H-246 2- (OCH2CH = CH2) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-i H-247 2- (OCH2CH = C (CH3) 2) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-i H-248 2- (OCH2CECH) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-i H-249 2- (OAc) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-i H-250 2- (OCO / Pr) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-i H-251 2- (OCONH Pr) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-i H-252 24OSO2CF3) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-i H-253 2- (NHCH / Pr) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-i H-254 2- (CO2Et) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-i H-255 2- (CO2 ⁱ Pr) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-i H-256 2- (Y ⁿ Pr) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-i
Petition 870170092471, of 11/29/2017, p. 88/143
86/134
Table 13
TABLE 1 (Continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE Cy2- (R ²⁰ ) p (R ²¹ ) r H-257 2 - ([1,3] dioxolan-2-yl) 4-CF3 CH2N (CH3) CH2 5-CF ₃ -pyridin-2-yl H-258 2- ⁿ Bu 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-yl H-259 2- (CH2CH = CH2) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-yl H-260 2- (CH2O ⁱ Pr) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-yl H-261 2- (CH2OEt) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-yl H-262 2- (OEt) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-yl H-263 2- (O ⁿ Pr) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-yl H-264 2- (O ⁱ Pr) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-yl H-265 2- (O ⁿ Bu) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-yl H-266 2- (O ^s Bu) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-yl H-267 2- (OCH2 ^S Bu) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-yl H-268 2- (OCH2 ^t Bu) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-yl H-269 24OCH2CF3) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-yl H-270 2- (OCH2CN) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-yl H-271 2- (OCH2CH (OH) CH3) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-yl H-272 2- (OCH2CH (OCH3) CH3) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-yl H-273 24OCH2OCH3) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-yl H-274 2- (OCH (CH3) OCH3) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-yl H-275 2- (OCH2Ac) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-yl H-276 2- (OCH2CH = CH2) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-yl H-277 2- (OCH2CH = C(CH3) 2) 4-CF3 CH2OCH2 5-CF3-pyridin-2-yl
[Table 14]
TABLE 1 (Continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE Cy2- (R ²⁰ ) p (R ²¹ ) r H-278 2- (OCH2CECH) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-yl H-279 2- (OAc) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-yl H-280 2- (OCO2'Pr) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-yl
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TABLE 1 (Continued) H-281 2- (OCONH Pr) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-i H-282 24OSO2CF3) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-i H-283 2- (NHCH / Pr) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-i H-284 2- (CO2Et) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-i H-285 2- (Y ⁿ Pr) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-i H-286 2 - ([1,3] dioxolan-2-yl) 4-CF3 CH2OCH2 5-CF ₃ -pyridin-2-i H-287 2- ⁿ Bu 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-i H-288 2- (CH2CH = CH2) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-i H-289 2- (CH2O ⁱ Pr) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-i H-290 2- (CH2OEt) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-i H-291 2- (OEt) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-i H-292 2- (O ⁿ Pr) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-i H-293 2- (OPr) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-i H-294 2- (O ⁿ Bu) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-i H-295 2- (O ^s Bu) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-i H-296 2- (OCH / Pr) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-i H-297 2- (OCH2 ^C Pr) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-i H-298 2- (OCH2 ^S Bu) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-i H-299 2- (OCH2 ^t Bu) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-i H-300 24OCH2CF3) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-i H-301 2- (OCH2CN) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-i
[Table 15]
TABLE 1 (Continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE Cy2- (R ²⁰ ) p (R ²¹ ) r H-302 2- (OCH2CH (OH) CH3) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-yl H-303 2- (OCH2CH (OCH3) CH3) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-yl H-304 24OCH2OCH3) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-yl H-305 2- (OCH (CH3) OCH3) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-yl H-306 2- (OCH2Ac) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-yl H-307 2- (OCH2CH = CH2) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-yl
Petition 870170092471, of 11/29/2017, p. 90/143
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H-308 2- (OCH2CH = C (CH3) 2) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-yl H-309 2- (OCH2CECH) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-yl H-310 2- (OAc) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-yl H-311 2- (OCO / Pr) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-yl H-312 2- (OCONH Pr) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-yl H-313 24OSO2CF3) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-yl H-314 2- (NHCH / Pr) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-yl H-315 2- (CO2Et) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-yl H-316 2- (CO ₂ Pr) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-yl H-317 2- (Y ⁿ Pr) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-yl H-318 2 - ([1,3] dioxolan-2-yl) 4-CF3 CH2CF2CH2 5-CF ₃ -pyridin-2-yl H-319 2- ⁿ Bu 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-yl H-320 2- (CH ₂ CH = CH ₂ ) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-yl
[Table 16]
TABLE 1 (Continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE Cy2- (R ²⁰ ) p (R ²¹ ) r H-321 2- (CH ₂ OPr) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-i H-322 2- (CH ₂ OEt) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-i H-323 2- (OEt) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-i H-324 2- (O ⁿ Pr) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-i H-325 2- (OPr) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-i H-326 2- (O ⁿ Bu) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-i H-327 2- (O ^s Bu) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-i H-328 2- (OCH2 ^S Bu) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-i H-329 2- (OCH2 ^t Bu) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-i H-330 24OCH2CF3) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-i H-331 2- (OCH ₂ CN) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-i H-332 2- (OCH ₂ CH (OH) CH3) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-i H-333 2- (OCH ₂ CH (OCH3) CH3) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-i H-334 24OCH2OCH3) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-i
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89/134
TABLE 1 (Continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE Cy2- (R ²⁰ ) p (R ²¹ ) r H-335 2- (OCH (CH3) OCH3) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-yl H-336 2- (OCH2Ac) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-yl H-337 2- (OCH2CH = CH2) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-yl H-338 2- (OCH2CH = C (CH3) 2) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-yl H-339 2- (OCH2CECH) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-yl H-340 2- (OAc) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-yl H-341 2- (OCO2'Pr) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-yl [Tabe to 17]
TABLE 1 (Continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE Cy2- (R ²⁰ ) p (R ²¹ ) r H-342 2- (OCONH Pr) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-i H-343 24OSO2CF3) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-i H-344 2- (NHCH2'Pr) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-i H-345 2- (CO2Et) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-i H-346 2- (Y ⁿ Pr) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-i H-347 2 - ([1,3] dioxolan-2-yl) 4-CF3 CH2SCH2 5-CF ₃ -pyridin-2-i H-348 2- ⁿ Bu 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-i H-349 2- (CH2CH = CH2) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-i H-350 2- (CH2OPr) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-i H-351 2- (CH2OEt) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-i H-352 2- (OEt) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-i H-353 2- (O ⁿ Pr) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-i H-354 2- (OPr) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-i H-355 2- (O ⁿ Bu) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-i H-356 2- (O ^s Bu) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-i H-357 2- (OCH2 ⁱ Pr) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-i H-358 2- (OCH2 ^C Pr) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-i H-359 2- (OCH2 ^S Bu) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-i H-360 2- (OCH2 ^t Bu) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-i
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TABLE 1 (Continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE Cy2- (R ²⁰ ) p (R ²¹ ) r H-361 2- (OCH2CF3) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-yl H-362 2- (OCH2CN) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-yl H-363 2- (OCH2CH (OH)CH3) 4-CF3 CH2C (CH3) 2CH2 5-CF3-pyridin-2-yl
[Table 18]
TABLE 1 (Continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE Cy2- (R ²⁰ ) p (R ²¹ ) r H-364 2- (OCH2CH (OCH3) CH3) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-yl H-365 2- (OCH2OCH3) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-yl H-366 2- (OCH (CH3) OCH3) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-yl H-367 2- (OCH2Ac) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-yl H-368 2- (OCH2CH = CH2) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-yl H-369 2- (OCH2CH = C (CH3) 2) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-yl H-370 2- (OCH2CECH) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-yl H-371 2- (OAc) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-yl H-372 2- (OCO2 ⁱ Pr) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-yl H-373 2- (OCONH ⁱ Pr) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-yl H-374 2- (OSO2CF3) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-yl H-375 2- (NHCH2 ⁱ Pr) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-yl H-376 2- (CO2Et) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-yl H-377 2- (CO2 ⁱ Pr) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-yl H-378 2- (Y ⁿ Pr) 4-CF3 CH2C (CH3) 2CH2 5-CF ₃ -pyridin-2-yl H-379 2 - ([1,3] dioxolan-2-il) 4-CF3 CH2C (CH3) 2CH2 5-CF3-pyridin-2-yl Form the chemistry 34
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(R ²⁰ ),> y,
O 21 (R) r (Ui) [Table 191 TABLE 2
At the. THE Cy ^; - «X J-21 24OCH ₂ Pr) 4-CF ₃ C ₃ H ₃ 5-CF ₃ - pyridin -2- il - J-22 2-COCHj’Pr) 4-CF ₃ HERE 5-CF ₃ - pyridin -Z- il - J-23 2-; cHjOchíoch ₃ ) ch ₃ ) 4-CF ₃ HERE 5-CF ₃ - pyridin ~ 2 ~ il - J-24 2- (00 / Pr) 4-CF ₃ here 5-CF ₃ - pyridin -2- il - J-25 24OCH ₂ Pr) 4-CF ₃ HERE 6-CF ₃ -pyridazin -3- yl - J-26 2-ÍOCH / Pr) 4-CF ₃ c ₃ h ₅ 6-CF ₃ - pyridazirt -3- il - J-27 2-; ch _i och (och ₃ ) ch ₃ ) ^ -cf ₃ HERE 6-CF ₃ -pyridazin -3- yl - J-28 2- (CO / Pr) 4-CF ₃ HERE 6-CF ₃ - pyridazin -3- il - J-29 2-COCHjPr) 4-CF ₃ HERE 5 — CF ₃ - pyrimidin-2-yl - J-30 2-COCH / Pr) 4-CFj here 5-CF ₃ -pyrimidin-2-yl - J-31 2-; ch ₃ och (och ₃ ) ch ₃ ) 4-CF ₃ here 5-CF ₃ -pyrimidin-2-yl - J-32 2- (00 / Pr) 4-CF ₃ HERE 5-CF ₃ - pyrimidin-2-yl - J-33 2-ÍOCH; Pr) 4-CF ₃ HERE 5-CF ₃ - thiazol-2-yl - J-34 2- (OCH ₂ 'Pr) 4-CF ₃ HERE 5-CF ₃ - thiazol-2-yl - J-35 2- (CH ₂ OCH (OCH ₃ ) CH ₃ ) 4-CF ₃ HERE 5-CF ₃ - thiazol-2-yl - J-36 2- (CO / Pr) 4-CF ₃ HERE 5-CF ₃ - thiazol-2-yl - J-37 2-; OCH _: Pr) 4-CF ₃ HERE 5-CF ₃ - [1.3.4] thiadiazol-2-yl - J-38 2- / OCHj ^: Pr) 4-CF ₃ here 5-CF ₃ - [1.3.4] thiadiazol-2-yl - J — 39 2-; cHjOchcoch ₃ ) ch ₃ ) 4-CF ₃ here 5-CF ₃ - [1.3.4] thiadiazo) -2-yl - J-40 2- (00 / Pr) 4-CF ₃ HERE 5-CF ₃ - [1.3.4] thiadiazol-2-yl - J-41 2- (OCH _: Pr) 4-CF ₃ ch ₂ och ₂ 5-CF ₃ - pyridin -2- il - J-42 2- (OCH / Pr) 4-CF ₃ ch ₂ och ₂ 5-CF ₃ - pyridin ~ 2 ~ il - J-43 2-; ch ₂ och; och ₃ ) ch ₃ ) 4-CF ₃ CH ₂ OCH ₂ 5-CF ₃ - pyridin -2- il - J-44 2- {C0 / Pr) 4-CF ₃ CHjOCHj 5-CF ₃ - pyridin -2- il - J-45 2 ^ OCH ₂ Pr) 4-CFj CHjOCHj 6-CFj- pyridazin -3- yl -
Petition 870170092471, of 11/29/2017, p. 94/143
92/134 [Table 201 TABLE 2 (Continued)
At the (* ”)„ THE c / -c = f% (P ¹¹ ), J-46 2-COCHj'Pr) 4-CF ₃ CHjOCHj 6-CFj-pyridazin -3- yl - J-47 2-CC-í ₂ OCH (OCH3) CHj) 4-CFj CH ₂ OC-i ₂ 6-CFj- pyridazin -3- yl - J-48 2-ÍCOj'Pr) 4-CFj CHjOCH; 6-CFj- pyridazin -3- yl - J-49 Z-ÍOCH / Pr) 4-CF ₃ CHjOCHj 5-CFj-pyrimidin-2-yl - J-50 2-ÍOCH / Pr) 4-CFj Cl ₂ OC-i ₂ 5 ~ CFj- ptrimidin-2-yl - J-51 Z-ÍC-ijOCHCOCHjJCHj) 4-CFj CHjOCH; 5-CFj- primidin-2-yl - J-52 2-ÍCO ₂ 'Pr) 4-CFj CHjOCHj 5-CF ₃ - pyrimidin-2-yl - J-53 2-ÍOCHj'Pr) 4-CFj CHjOCHj 5-CFj- 1Ϊ3ζοΙ-2-ιΙ - J-54 2-ÍOCH / Pr) 4-CFj CHjOCH; 5-CFj- thiazol-2-yl - J-55 Z-IC-IIOCHIOCH ^ CHj) 4-CFj CHjOCHj 5-CF3- thiazol-2-yl - J-56 2-ÍCO ₂ 'Pr) 4-CFj CHjOCHj 5-CFj- thiazol-2-yl - J-57 2-CO CH j'Pr) 4-CFj CHjOC-ij 5-CFj-[1.3.4] thiadiazol-2-yl - J-58 2-COCH _; ^c Pr) 4-CFj CHjOC-ij 5-CFj-[1.3.4] thiadiazol-2-yl - J-59 Z-CC- ^ OC-IOCHjCHi) 4-CFj CHjOCHj 5-CFj-[1.3.4] thiadiazol-2-yl - J-60 2-ÍCO / Pr) 4-CFj Ch _; OC “í ₂ 5-CFj-[l, 3.4] thiadiazol-2-yl -
[Table 21]
TABLE 2 (Continued) At the. (R ¹ °) m (R ¹¹ ) n THE Cy ² - (R ^2Ü ) _P (R ² ) r J-61 2- (CO ₂ CH ₃ ) 4-CF ₃ C ₃ Hg 5-CF ₃ -pyridin-2-yl J-62 2- (OCH ₂ 'Pr) 4-CF ₃ C ₃ Hg 5-CN-pyridin-2-yl J-63 2- (0Et) 4-CF ₃ C ₃ H _S 5-CF ₃ -pyridin-2-yl J-64 2- (O ⁿ Pr) 4-CF ₃ C ₃ H _S 5-CF ₃ -pyridin-2-yl J-65 2- (OCH ₂ OCH ₃ ) 4-CF ₃ C ₃ H _S 5-CF ₃ -pyridin-2-yl J-66 2- (OCH ₂ 'Pr) 4-CF ₃ C ₃ H ₆ S-CN-pyridazin-3-yl J-67 2-OH 4-CF ₃ C ₃ H _s 5-CF ₃ -pyridin-2-yl J-68 2- (O ⁿ Bu) 4-CF ₃ C ₃ H _S 5-CF ₃ -pyridin-2-yl J-69 2 - ([1,3] dioxolan-2-yl) 4-CF ₃ C ₃ H _S 5-CF ₃ -pyridin-2-yl J-70 2- (CH ₂ O'Pr) 4-CF ₃ C ₃ H _S 5-CF ₃ -pyridin-2-yl J-71 2- (CH ₂ OCH ₃ ) 4-CF ₃ C ₃ H _S 5-CF ₃ -pyridin-2-yl J-72 2- (CH ₂ OEt) 4-CF ₃ C ₃ H _S 5-CF ₃ -pyridin-2-yl
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93/134
TABLE 2 (Continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE Cy ² - (R ²⁰ ) p (R ²¹ ) r J-73 2- (NHCH ₂ Pr) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl J-74 2- (OPr) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl J-75 2- (O ^s Bu) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl J-76 2- (OCO / Pr) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl J-77 2 / OCH2CF3) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl J-78 2- (OCH2CH = CH2) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl J-79 2- (OCH2CH = C (CH3) 2) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl J-80 2- (OCH ₂ ^t Bu) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl J-81 2- (OCH2CH = CCl2) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl J-82 2- (OCH2CECH) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl J-83 2- (OCH2C (CH3) = CH2) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl J-84 2- (OCH ₂ ^s Bu) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl J-85 2- (OCH2CN) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl J-86 2- (OCH (CH) OCH) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl J-87 2- (CO2Et) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl
[Table 22]
TABLE 2 (Continued) J-88 2- (OAc) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl J-89 2- (OCH ₂ [2,2-Cl ₂ -3-Ph- ^c Pr]) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl J-90 2- (OCH ₂ Ac) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl J-91 2- (OCH2CH (OH) CH3) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl J-92 2- (OCH2CH (OCH3) CH) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl J-93 2- (The ^c Pen) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl J-94 2- (OCONH 'Pr) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl J-95 2 / OSO2CF3) 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl J-96 2-Ph 4-CF3 C3H6 5-CF ₃ -pyridin-2-yl
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TABLE 2 (Continued) J-97 2- (pyridin-3-yl) 4-CF ₃ c ₃ h _s 5-CF ₃ -pyridin-2-yl J-98 2- (Y ⁿ Pr) 4-CF3 c ₃ h _s 5-CF ₃ -pyridin-2-yl J-99 2- (CH ₂ CH = CH ₂ ) 4-CF3 c ₃ h _s 5-CF ₃ -pyridin-2-yl J-100 2- (O ⁿ Pr) 4-CI c ₃ h _s 5-CF ₃ -pyridin-2-yl J-101 2- (O ⁿ Pr) 4-CF3 c ₄ h ₈ 5-CF ₃ -pyridin-2-yl J-102 2- (OCH ₂ 'Pr) 4-CI ch ₂ och ₂ 5-CF ₃ -pyridin-2-yl
Chemical formula 35
/ (R) n

(R) _r (Π)
At the. Cy ' C = ' í = f’V THE Cy ² Λ Λ -í-5 pyridin -2- il - 5-CF ₃ c ₃ h ₆ Ph 2-ÍOC-i ₂ 'Pr) 4-CFj <-6 pyridin -2- il - 5-CF ₃ CjH _s Ph 2-fOC-t / Pr) 4-CF ₃ <-7 pyridin -2- í | - 5-CF ₃ C; Hí Ph 2- (CH _i OCH: oCH _s 3CH33 4-CF, <-a pyridin -2- il - 5-CF3 C ₃ H _£ Ph 2-! CO ₂ 'Pr) 4-C-3 <-9 pyridin -2- il - 5-CF3 CHjOCHí Ph 2- (OC-i ₂ Pr) 4-C5 <-10 pyridin -2- il - 5-CF; CHjOCH; Ph 2-COCH / Pr) 4-CFj <-11 pyridin -2- il - 5-CF ₃ C-1 ₂ OC-1 ₂ Ph Z-tCHjOC-iiOCrljlCHj) 4-CFj <-12 pyridin -2- il - 5-CFj CHjOC-II Ph 2-ÍCOj'Pr) 4-CF, <-13 pyridazin -3- il - 6-CF3 Ph 2- (OCrl ₂ ^! Pr) 4-CF3 <-19 pyridazin -3- il - 6-CF3 c _{£ 3} Ph 2-fOCVPr) 4-CFj <-20 pyridazin -3- il - 6-CF3 C ₃ H _t Ph 2-fCH ₂ OC- <OCr (j) CH ₃ l 4-CFj <-21 pyridazin ~ 3 il - 6-CFj Ο _3. -Ι _£ Ph Z-ÍCO ₂ 'Pr) 4-CFj <-22 pyridazin -3- il - 6-CF ₃ CHiOCH ₂ Ph 2- (OCH ₂ Pr> 4-C5 <-23 pyridazin -3- il - 6-CF3 CHiOCHí Ph 2-ÍOC-l / Pr) 4-C-3 <-24 pyridazin 3 * il - 6-CF ₃ C-1 ₂ OC-1 ₂ Ph 2- <Cl ₂ OC <IOC-l3 / CHj) 4-CF3 <-25 piridazin -3 il - 6-CF ₃ CH ₂ OCH ₂ Ph 2-ÍCOj’Pr) 4-CFj <-30 pyridin -2- il - 5-C c ₃ h _s Ph 2- (OC-i ₂ Pr) 4-CFj <-31 pyridin -2- il - 5-C c ₃ h « Ph 2-ÍOCH / Pr) 4-cf, <-32 piricin -2- il - 5-C CjHs Ph 2-ICH0C4; 0C-TiCHs) 4-C-s <-33 pyridin ~ 2 ~ il - 5-C c ₃ h ₆ Ph Z-ÍCO ₂ 'Pr) 4-CFj <-34 pmdin -2- il - 5-C ch ₂ och ₂ Ph 2- (OCH ₂ Pr) 4-CFj <-35 pyridin -2- il - 5-CN1 CHiOC-II Ph 2-COCH ₂ 'Pr) 4-CFj <-3S pyridin -2- il - 5-C CH ₂ OCH ₂ Ph 2- (CH ₂ OC: -KOC Hj) C Hj) 4-CF3 <-37 pyridin -2- il - 5-C ch ₂ och ₂ Ph 2-ÍCOj'Pr) 4-CF3
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95/134 [Table 24] TABLE 3 (Continued)
At the. Cy ' THE Cy ¹<R ^I0 ) _and K-38 piridín —3- μ 2- / O ⁿ Pr) 6-CF, C, H, pyridin -2- il - 5-CFj K-39 pyrazol-5-il 1-Bu 3-CF, C ₃ H, pyridin -2- il - 5-CFj K-40 pyrazole5-il 1- (CH ₂ 'Pr) 3-CFj C, H, piridín -2- íl - 5-CFj K-41 pyrazol-5-il 1-ÍCH / Pr) 3-CFj CíHj pyridin -2- il - 5-CFj K-42 pyrazol-5-il 1- (CHjOCHjOCHj) 3-CFj C, H, pyridin -2- íl - 5-CFj K-43 pyrazol-5-il I-CCHjOCHCOCHjJCH,) 3-CFj C ₃ H, pyridin -2- il - 5-CFj K-44 pyrazol-5-il 1-ÍCH (OCHj) CHj) 3-CFj C, H, pyridin -2- il - 5-CFj K-45 pyrazole5-il Ι-ΐΟΟ / Pr) 3-CFj CjHj pyridin -2- il - 5-CFj K-46 pyrazole5-il 1- (CH ₂ CH (OCH,) ₂ ) 3-CFj C, H, pyridin -2- il - 5-CFj K-47 pyrazol-5-il 1 - ([l.3] dioxolan-2-yl) 3-CFj C ₃ H, pyridin -2- il - 5-CFj K-48 pyrazol-5-il 2- (CH; 'Pr) 3-CFj C, H, pyridin -2- il - 5-CFj K-49 pyrazol-5-il 2 “ÍCHj ^S Pr) 3-CFj CjHj pyridin -2- il - 5-CFj K-50 pyrazol-5-il 2-Bu 3-CFj C, H, pyridin -2- il - 5-CFj K-5T pyrazol-5-íl 2- (CH ₂ OCH ₂ OCH ₃ ) 3-CFj C ₃ H, pyridin -2- íl - 5-CFj K-52 pyrazol-5-il 2- (ΟΗ ₂ ΟΟΗ (ΟΟΗ, ΧΪΗ ₃ ) 3-CFj C) H _{ pyridin -2- il - 5-CFj K-53 pyrazol-5-il 2- (CH (OCH ₃ ) CH ₃ ) 3-CFj CjHj pyridin -2- il - 5-CFj K-54 pyrazol-5-il 2-ÍCO / Pr) 3-CFj C, H, pyridin -2- íl - 5-CFj K-55 pyrazol-5-il 2-CCH ₂ CH (OCH ₃ ) ₂ ) 3-CFj C ₃ H, pyridin -2- il - 5-CFj K-56 pyrazol-5-il 2-C (1.3] dioxolan-2-yl) 3-CFj C, H, pyridin -2- il - 5-CFj K-57 pyrazol-5-il 1.3- «5ΗΛ - CíHj pyridin -2- il - 5-CFj K-58 pyrazol-5-il 1- ° Bu-3-CH ₃ - Ο, Η, pyridin -2- il - 5-CFj K-59 pyrazol-5-il 1-CH _S 3-CFj C ₃ H ₅ pyridin -2- il - 5-CFj K-60 pyrazol-5-il 1-Et 3-CFj CjH, pyridin -2- il - 5-CFj K-61 pyrazol-5-il 1-Pr 3-CFj CaH, pyridin -2- il - 5-CFj K-62 pyrazol-5-íl 1-Pen 3-CFj Ο, Η, pyridin -2- il - 5-CFj
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96/134 [Table 25] TABLE 3 (Continued)
At the. Oy ' GO'% <R ^H ) _n THE Cy ²ir ²⁰ ; K-63 pyrazol-5-il 1-Hex 3-CF, C ₃ H ₆ pyridin -2- il - 5-CF ₃ K-64 pyrazole5-i) 1-'Pr 3-CF ₃ C ₃ H ₆ pyridin -2- il - 5-CF ₃ K-65 pyrazol-5-il 3-CF ₃pyridin -2- il - 5-CF ₃ K-66 pyrazole-S-jJ 1- (CH ₂ C h = ch ₂ ) 3-CF ₃ c ₃ h ₈ pyridin -2- il - 5-CF ₃ K-67 pyrazole-5-i I 1- (CH ₂ CN) 3-CF ₃ CrçHg pyridin -2- il - 5-CF ₃ K-68 pyrazole-5-i I 1-C (CH ₂ ) ₃ CN) 3-CFj C ₃ H ₈ pyridin -2- il - 5-CF ₃ K-69 pyrazole-5-i I 1-Bn 3-CF ₃ c ₃ h _s pyridin -2- il - 5-CF ₃ K-70 pyrazole5-i I 1 - (2-CI-Bn) 3-CF ₃ c ₃ h ₆ pyridin -2 il - 5-CF ₃ K-71 pyrazol-5-íl 1-Ph 3-CF, C ₃ H _b pyridin -2- il - 5-CF ₃ K-72 pyrazol-5-il 1 - (3 — Cl — Ph) 3-CF ₃ c ₃ h ₆ pyridin -2- il - 5-CF ₃ K-73 pyrazole-5-i I 1- (3,5-CI ₂ -Ph) 3-CF ₃pyridin -2- il - 5-CF ₃ K-74 pyrazol-5-il 1 - (Py-2-yl) 3-CF ₃ c ₃ h ₆ pyridin -2- il - 5-CF ₃ K-75 pyrazol-5-il 1-Bu 3-CF ₃ 4—01 6385 pyridin -2- il - 5-CF ₃ K-76 pyrazol-5-il 1-Bu 3-CF,4-Br C ₃ H ₈ pyridin -2- il - 5-CF ₃ K-77 pyrazol-5-il 1-Bu-4-Ph 3-CF ₃ c ₃ h ₆ pyridin -2- il - 5-CF ₃ K-78 pyrazole - 5-il 1-CH ₃ -4- (CHO) 3-CF ₃ C ₃ H _b pyridin -2- il - 5-CF ₃ K-79 pyrazol-5-il 1-CH ₃ -4-CCH = NOCH ₃ ) 3-CF ₃ θ3 ^ 6 pridin -2 il - 5-CF ₃ K-80 pyrazol-5-il 1-Bu-4- (CHO) 3-CF ₃ CaH ₈ pyridin -2- il - 5-CF ₃ K-81 pyrazol-5-il 1-Bu-3-Ph - c ₃ h ₆ pyridin -2- il - 5-CF ₃ K-82 pyrazol-5-il 1- ⁿ Bu-3-C3-CI-Ph) - pyridin -2- il - 5-CF ₃ K-83 pyrazole5-il 1-Bu-3-C4-CI-Ph) - c ₃ h ₆ pyridin -2- il - 5-CF ₃ K-84 pyrazol-5-il 1-Bu-3-C3.4-dj-Ph) - c ₃ h _s pyridin -2- il - 5-CF ₃ K-85 pyrazol-5-il I ^ Bu-S-O.Õ-dj-Ph) - c ₃ h ₆ pyridin -2- il - 5-CF ₃
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97/134 [Table 26] TABLE 3 (Continued)
At the. Cy ‘ (R ’% THE Cy ^! <FA _r (R “)„ K-86 pyrazol-5-il 1-Bu 3-CFj HERE pyridin -2- il - 5-CN K-87 pyrazol-5-yl 1-Bu 3-CF, C ₃ H _S pyridin -2- íl 5-NOj - K-88 pyrazol-5-il t- {3-CF _s -Ph) 3-CF, here pyridin -2- il - 5-CF, K-89 pyrazol-5-il l-O-CHj-Ph) 3-CF: here pyridin -2- il - 5-CF, K-90 pyrazol-5-il 1- (Py-2-tl) 3- (3.4.5-F ₃ -Ph) - HERE pyridin -2- il - 5-CF, K-91 pyrazol-5-il 1- {Py-2-yl) 3- (3.5-F ₂ -Ph) - C ₃ H _s pyridin -2- il - s-cf ₃ K-92 pyrazol-5-il 1- (3-CI-Py-2-yl) 3-CF ₃ here pyridin -2- il - 5-CF, K-93 pyrazol-5-il 1- (6-CH ₃ -Py-2-yl) 3-CF ₃ c ₃ h _s pindin ~ 2 ~ il - 5-CF, K-94 pyrazol-5-il 1- (4-CF ₃ - thiazol -2-yl) 3-CFj C ₃ H ₆ pyridin -2- il - 5-CF, K-95 pyrazole - 5-il 1.4-CCH _a ) _a 3-CF, HERE pyridin -2- il - 5-CF, K-96 pyrazol-5-il 1-CH ₃ -4- (CH ₂ OH) 3-CF, HERE pyridin -2- il - s-cf ₃ K-97 pyrazole - 5-il 1-Bu-4-CH, 3-CF ₃ HERE pyridin -2- il - 5-CF, K-98 pyrazole - 5-il 1- _n Bu 3- (3.5- (CF ₃ ) ₂ -Ph) - HERE pyridin -2- il - 5-CF, K-99 pyrazol-5-il 1-Bu-3- (3.5-F ₂ -Ph) - HERE pyridin -2- il - 5-CF, K-100 pyrazol-5-il 1- ° Bu-3- (3.4.5-F _s -Ph) - HERE pyridin -2 ~ il - 5-CF, K-1 01 pyrazol-5-il 1,4- (CH,) ₂ -3- (CO ₂ Et) - HERE pindin ~ 2 ~ il - 5-CF, K-102 pyrazol-5-il 1-CH, 4-CI3-CF, here pyridin -2- il - 5-CF, K-1 03 pyrazol-5-il - 3-CF-, HERE pyridin ~ 2 ~ il - 5-CF, K-1 04 pyrazol-5-il 1- (C (= O) ‘Bu) 3-CF: HERE pyridin ~ 2 ~ il - 5-CF, K-1 05 pyrazol-5-il 1 - (Py-2-yl) 3-C3.5-CI ₂ -Ph) - HERE pindin -2- il - 5-CF, K-1 06 pyrazol-5-il l-tCHjOCHj) 3-CFj HERE pyridin -2- il - 5-CF,
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98/134 [Table 27] TABLE 3 (Continued)
At the. Cy 'CFl ”) _n THE Cy ² <FA, A ') _o K-107 pyrazol-5-il 1-ÍCHjOEt) 3-CFj HERE pyridin -2- il - 5-CF; K-108 pyrazole · 5-íl 1- (CH ₂ CH ₃ OCH ₃ ) 3-CFj C _S H _S pyridin -2- il - 5-CFj K-109 pyrazol-5-yl 1-CCHjCHjOEt) 3-CFj HERE pyridin -2- il - 5-CFj K-110 pyrazol-5-il 1-CHCH (OEt) _z ) 3-CF ₃ CjH _s pyridin -2- il - 5-CF _s K-111 pyrazol-5-il 1- (CH, CH ₈ CH (OCH,) P 3-CF ₃ HERE pyridin -2- il - 5-CFj K-112 pyrazol-5-il lUCH ₂ CH ₂ CH (OEt) ₂ ) 3-CFj HERE pyridin -2- il - 5-CFj K-113 pyrazol-5-il 1-ÍCH ₂ ([1.3] dioxolan-2-yl)) 3-CF ₃ HERE pyridin -2- il - 5-CF ₃ K-114 pyrazol-5-il 1 — CC HjCtetrahy dro-fvi ran-2ii » 3-CFj here pyridin -2- il - 5-CF3 K-115 pyrazol-5-il 1- (CHjCHj ([1,3,3] dioxolan-2il)> 3-CFj HERE pyridin -2- il - 5-CF3 K-116 pyrazol-5-il 1- (CHjCHj ([1, 3] dioxan-2il)) 3-CFj HERE pyridin -2- il - 5-CF3 K-117 pira20l-5.il 1 —Ac 3-CF, HERE pyridin -2- il - 5-CF ₃ K-118 pyrazol-5-il 1- (C (= O) Et) 3-CF ₃ HERE pyridin -2- il - 5-CF ₃ K-119 pyrazol-5-il 1- «X = 0rPr) 3-CF ₃ HERE pyridin -2- il - 5-CF3 K-1 20 pyrazol-5-il 1- (C (= O) Bu) 3-CF ₃ HERE pyridin -2- il - 5-CF ₃ K-1 21 pyrazol-5-il 1- (C (= O) Ph) 3-CF ₃ CjH; pyridin -2- il - 5-CFj K-1 22 pyrazol-5-il 1- (COjCH ₃ ) 3-CF ₃ here pyridin ~ 2 ~ il - 5-CF3 K-1 23 pyrazol-5-il 1-CC0; Et) 3-CF ₃ HERE pyridin -2- il - 5-CFj K-1 24 pyrazol-5-il l-CCO / Pr) 3-CF ₃ here pyridin -2- il - 5-CF3 K-1 25 pyrazol-5-il 1- (CO ₂ Bu) 3-CF ₃ HERE pyridin -2- il - 5-CFj K-1 26 pyrazol-5-il KCHjCHO) 3-CF ₃ HERE pyridin -2- il - 5-CF3 K-1 27 pyrazol-5-il HCHjCHjCHO) 3-CF ₃ HERE pyridin -2- il - 5-CFj
[Table 28] TABLE 3 (Continued)
At the. Cy ’ Í3 ”) _b THE Cy ^{2 2} ') _r (R ²⁰ ) „ K-128 pyrazol-5-il 1 -CH ₃ -4- (CH = NOH) 3-CF ₃ HERE pyridin -2- il - 5-CF3 K-129 pyrazol-5-il 1-CH ₃ -4- (CH = NOEt) 3-CF, HERE pyridin -2- il - 5-CF ₃ K-130 pyrazol-5-il 3- (3.5-F _to -Ph) - HERE pyridin -2- il - 5-CF ₃ K-131 pyrazol-5-il 1- {CH ₂ CH (OCHj) p-3- (3,5-F ₂ -Ph) - HERE pyridin -2- il - 5-CF ₃ K-132 pyrazol-5-yl 1- (CH _z 0.3] dioxolan-2-yl)) - 3-C3.5-F ₂ -Ph) - HERE pyridin -2- il - 5-CF ₃ K-133 pyrazol-5-il 1- {Py-2-'1) -3- (thiophen 2 H) - HERE pyridin -2- il - 5-CF ₃ K-134 pyrazol-5-il 1-CCH ₂ CHjCH = CHj) 3-CF ₃ HERE pyridin -2- il - 5-CF3 K-135 pyrazol-5-il 1- (CHjCHjCH (Et) j) 3-CF, HERE pyridin -2- il - 5-CF ₃ K-136 pyrazol-5-il 1-Pen 3-CF ₃ here pyridin -2- il - 5-CF ₃
Chemical formula 36
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-O (R ¹¹ ) n ^Z ₂ / ^r20 v (R) r (Ij) [Table 29] TABLE 4
At the Cy ' <= T '„ THE Cy ¹ L-5 pyridin -2- il - 5-CF, Pb 2-; οοη ₂ ^! Ργ) 4-CF, L-6 pyridin -2- il - 5-CF, hjFl _s Pb 2-ÍOCH / Pr) 4-CF, L-7 pyridin -2- il - 5-CF, C, H _S Pb 2-: ch _i och: och ₃ ; ch ₃ ) 4-CF, L-S pyridin ~ 2 ~ il - 5-CF, C, H _S Pb 2-CCO / Pr) 4-CF, L-S pyridin -2- il - 5-CF, CHjOCH ₂ Pb 2-ÍOCH, 'Pr) 4-CF, L-10 pyridin -2- il - 5-CF, ch ₂ och ₂ Pb 2 — ÍOCHj ^í Pr; 4-CF, L-11 pyridin -2- il - 5-CF, ch ₂ och ₂ Pb 2-; ch ₂ och; och,; ch,) 4-CF, L-12 pyridin -2- il - 5-CF, ch ₂ och ₂ Pb 2-CCO / Pr) 4-CF, L-13 pindazin -3- il - 6-CF, U, Pb 2-; ocH; pr) 4-CF, L-19 pyridazin -3- il - S-CF, C, H _and Pb 2-: ocH ₂ ^and Pr: · 4-CF, L-20 pyridazin -3- il - 6-CF, C, H _and Pb 2-; ch _i ochoch,: ch ₃ ) 4-CF, L-21 pyridazin -3- il - 6-CF, C, H, Pb 2 <οο; ργ) 4-CF, L-22 pyridazin -3 * il - 5-CF, CHjOCH, Pb Í-ÍOCK / Pr) 4-CF, L-23 pyridazin -3- il - 6-CF, CH ₂ 0CM ₂ Pb 2-: OCH, ^s Pr; 4-CF, _-2í pyridazin -3- il - 6-CF, ch, ogh ₂ Pb 2-; ch _t och: och,; ch ₃ ) 4-CF, L-25 pyridazin -3- il - S-CF, CHjOCHj Pb 2-CCO / Pr) 4-CF,
[Table 30]
TABLE 4 (continued) At the. Cy ¹ (R Jm (R ¹¹ ) n THE Cy ² (R ² (R ² °) p L-26 pyridin-2-il - 5-CF ₃ C ₃ Hg Ph 2- (CO ₂ CH ₃ ) 4-CF ₃ L-27 pyridin-2-il - 5-CN C ₃ Hg Ph 2- (OCH ₂ 'Pr) 4-CF ₃ L-28 pyridin-2-il - 5-CF3 C ₃ Hg Ph 2- (0Et) 4-CF ₃ L-29 pyridin-2-il - 5-CF3 C ₃ Hg Ph 2- (O ⁿ Pr) 4-CF ₃ L-30 pyridin-2-il - 5-CF3 C ₃ Hg Ph 2- (OCH ₂ OCH ₃ ) 4-CF ₃ L-31 pyridazin-3-yl - 6-CN C ₃ Hg Ph 2- (OCH ₂ 'Pr) 4-CF ₃ L-32 pyridin-2-il - 5-CF3 C ₃ Hg Ph 2-OH 4-CF ₃ L-33 pyridin-2-il - 5-CF3 C ₃ Hg Ph 2- (O ⁿ Bu) 4-CF ₃
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TABLE 4 (continued) At the. Cy ¹ (R ¹⁰ ) m (R ¹¹ ) n THE Cy ² (R ²¹ ) r (R ²⁰ ) p L-34 pyridin-2-il - 5-CF3 C3H6 Ph 2 - ([1,3] dioxolan-2-yl) 4-CF3 L-35 pyridin-2-il - 5-CF3 C3H6 Ph 2- (CH ₂ O ⁱ Pr) 4-CF3 L-36 pyridin-2-il - 5-CF3 C3H6 Ph 2- (CH2OCH) 4-CF3 L-37 pyridin-2-il - 5-CF3 C3H6 Ph 2- (CH ₂ OEt) 4-CF3 L-38 pyridin-2-il - 5-CF3 C3H6 Ph 2- (NHCH ₂ ⁱ Pr) 4-CF3 L-39 pyridin-2-il - 5-CF3 C3H6 Ph 2- (O ⁱ Pr) 4-CF3 L-40 pyridin-2-il - 5-CF3 C3H6 Ph 2- (O ^s Bu) 4-CF3 L-41 pyridin-2-il - 5-CF3 C3H6 Ph 2- (OCO / Pr) 4-CF3 L-42 pyridin-2-il - 5-CF3 C3H6 Ph 2- (OCH ₂ CF3) 4-CF3 L-43 pyridin-2-il - 5-CF3 C3H6 Ph 2- (OCH ₂ CH = CH ₂ ) 4-CF3 L-44 pyridin-2-il - 5-CF3 C3H6 Ph 2- (OCH ₂ CH = C (CHs) 2) 4-CF3 L-45 pyridin-2-il - 5-CF3 C3H6 Ph 2- (OCH ₂ ^t Bu) 4-CF3 L-46 pyridin-2-il - 5-CF3 C3H6 Ph 2- (OCH ₂ CH = CCl ₂ ) 4-CF3 L-47 pyridin-2-il - 5-CF3 C3H6 Ph 2- (OCH ₂ ChCH) 4-CF3 L-48 pyridin-2-il - 5-CF3 C3H6 Ph 2- (OCH ₂ C (CH3) = CH ₂ ) 4-CF3 L-49 pyridin-2-il - 5-CF3 C3H6 Ph 2- (OCH ₂ ^s Bu) 4-CF3 L-50 pyridin-2-il - 5-CF3 C3H6 Ph 2- (OCH ₂ CN) 4-CF3 [Tabe to 31]
TABLE 4 (continued) At the. Cy ¹ (R ¹⁰ ) m (R ¹¹ ) n THE Cy ² (R ²¹ ) r (R ²⁰ ) p L-51 pyridin-2-il - 5-CF3 C3H6 Ph 2- (OCH (CH) OCH) 4-CF3 L-52 pyridin-2-il - 5-CF3 C3H6 Ph 2- (CO ₂ Et) 4-CF3 L-53 pyridin-2-il - 5-CF3 C3H6 Ph 2- (OAc) 4-CF3 L-54 pyridin-2-il - 5-CF3 C3H6 Ph 2- (OCH ₂ [2,2-Cl ₂ -3 - Ph- ^c Pr]) 4-CF3
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TABLE 4 (continued) At the. Cy ¹ (R Tm (R) n THE Cy ² (R ²¹ ) r (R ²⁰ ) p L-55 pyridin-2-il - 5-CF ₃ c ₃ h _s Ph 2- (OCH ₂ Ac) 4-CF3 L-56 pyridin-2-il - 5-CF3 c ₃ h _s Ph 2- (OCH ₂ CH (OH) ch ₃ ) 4-CF3 L-57 pyridin-2-il - 5-CF3 c ₃ h _s Ph 2- (OCH ₂ CH (OCH ₃ ) ch ₃ ) 4-CF3 L-58 pyridin-2-il - 5-CF3 c ₃ h _s Ph 2- (The ^c Pen) 4-CF3 L-59 pyridin-2-il - 5-CF3 c ₃ h _s Ph 2- (OCONH 'Pr) 4-CF3 L-60 pyridin-2-il - 5-CF3 c ₃ h _s Ph 2- (OSO ₂ CF ₃ ) 4-CF3 L-61 pyridin-2-il - 5-CF3 c ₃ h _s Ph 2-Ph 4-CF3 L-62 pyridin-2-il - 5-CF3 c ₃ h _s Ph 2- (pyridin-3-yl) 4-CF3 L-63 pyridin-2-il - 5-CF3 c ₃ h _s Ph 2- (Y ⁿ Pr) 4-CF3 L-64 pyridin-2-il - 5-CF3 c ₃ h _s Ph 2- (CH ₂ CH = CH ₂ ) 4-CF3 L-65 pyridin-2-il - 5-CF3 c ₃ h _s Ph 2- (O ⁿ Pr) 4-CI L-66 pyridin-2-il - 5-CF3 c ₄ h ₈ Ph 2- (O ⁿ Pr) 4-CF3 L-67 pyridin-2-il - 5-CF3 ch ₂ o ch ₂ Ph 2- (OCH ₂ 'Pr) 4-CI
Chemical formula 37 (R ¹ °) m (R
V 1 - ° Cy
M / ^N ° (R ²¹ ) _r (Ik)
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102/134 [Table 32] TABLE 5
At the. Cy IR ¹¹ ) _n THE Cy ² (R ^2, ) _r ír ² á M-5 Ph 2-COCH; Pr) 4-CF ₃ here pyridin -2- tl - 5-CF ₃ M-6 Ph 2-ÍOCH / Pr) 4-CFj here pyridin -2- tl - 5-CF ₃ M-7 Ph 2-; ch ₂ och; och ₃ ) chj) 4-CF ₃ here pyridin -2- il - 5-CF ₃ M-8 Ph 2-; CO _; Pr) 4-CF ₃ c ₃ h ₆ pyridin -2- il - 5-CF ₃ M-9 Ph 2-ÍOCH ₂ Pr) 4-CF ₃ CH ₂ OCH; pyridin -2- tl - 5-CF ₃ M-10 Ph 2-; OCH ₂ ⁼ Pr) 4-CF ₃ CH ₂ OCH; pyridin -2- il - 5-CF ₃ M-11 Ph 2-; ch ₂ och; och _; ) ch3) 4-CF ₃ CH ₂ OCH; pyridin -2- il - 5-CF ₃ M-12 Ph 2- (CO ₂ Pr) 4-CF ₃ CH ₂ OCH; pyridin -2- il - 5-CF ₃ M-1 7 Ph 2- (OCH ₂ Pr) 4-CF ₃ here pyridazin -3- il - 6-CF ₃ M-18 Ph 2-; OCH Pr) 4-CF ₃ HERE pyridazin -3- il - 6-CF ₃ M-19 Ph 2-; ch ₂ och; och,) cHj) 4-CF ₃ here pyridazin -3- il - 6-CF ₃ M-20 Ph 2- {CO; Pr) 4-CF ₃ HERE pyridazin -3- il - 6-CF ₃ M-21 Ph 2-ÍOCH; Pr) 4-CF ₃ CHjOCH; pindazin -3- il - 6-CF ₃ M-22 Ph 2-; 0CH / Pr) 4-CF ₃ CH ₂ OCH; pyridazin -3- il - 6-CF ₃ M-23 Ph 2-; ch ₂ och; och ₃ ) ch3) 4-CF ₃ CH ₂ OCH; pyridazin -3- il - 6-CF ₃ M-24 Ph 2-ÍC0 ₂ Pr) 4-CF ₃ CH ₂ OCH; piridazin -3 il - 6-CF ₃
[Table 33]
TABLE 5 (Continued) At the. Cy ¹ (R ^1ü ) _m (R) n THE Cy ² (R ² ) r (R ²⁰ ) p M-25 Ph 2- (CO ₂ CH ₃ ) 4-CF ₃ C ₃ Hg pyridin-2-il 5-CF ₃ M-26 Ph 2- (OCH ₂ 'Pr) 4-CF ₃ C ₃ Hg pyridin-2-il 5-CN M-27 Ph 2- (0Et) 4-CF ₃ C ₃ Hg pyridin-2-il 5-CF ₃ M-28 Ph 2- (O ⁿ Pr) 4-CF ₃ C ₃ Hg pyridin-2-il 5-CF ₃ M-29 Ph 2- (OCH ₂ OCH ₃ ) 4-CF ₃ C ₃ Hg pyridin-2-il 5-CF ₃ M-30 Ph 2- (OCH ₂ 'Pr) 4-CF ₃ C ₃ Hg pyridazin-3-yl 5-CN M-31 Ph 2-OH 4-CF ₃ C ₃ Hg pyridin-2-il 5-CF ₃ M-32 Ph 2- (O ⁿ Bu) 4-CF ₃ C ₃ Hg pyridin-2-il 5-CF ₃ M-33 Ph 2 - ([1,3] dioxolan-2-il) 4-CF ₃ C ₃ Hg pyridin-2-il 5-CF ₃ M-34 Ph 2- (CH ₂ O'Pr) 4-CF ₃ C ₃ Hg pyridin-2-il 5-CF ₃ M-35 Ph 2- (CH ₂ OCH ₃ ) 4-CF ₃ C ₃ Hg pyridin-2-il 5-CF ₃
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TABLE 5 (Continued) At the. Cy ¹ (R ¹⁰ ) m (R ¹¹ ) n THE Cy ² (R ²¹ ) r (R ²⁰ ) p M-36 Ph 2- (CH ₂ OEt) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-37 Ph 2- (NHCH ₂ 'Pr) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-38 Ph 2- (O'Pr) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-39 Ph 2- (O ^s Bu) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-40 Ph 2- (OCO ₂ 'Pr) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-41 Ph 2- (OCH2CF3) 4-CF3 C3H6 pyridin-2-il 5-CF3 [Tabe to 34]
TABLE 5 (Continued) At the. Cy ¹ (R ¹⁰ ) m (R ¹¹ ) n THE Cy ² (R ²¹ ) r (R ²⁰ ) p M-42 Ph 2- (OCH ₂ CH = CH ₂ ) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-43 Ph 2- (OCH ₂ CH = C (CH3) 2) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-44 Ph 2- (OCH ₂ ^t Bu) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-45 Ph 2- (OCH ₂ CH = CCl2) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-46 Ph 2- (OCH ₂ CECH) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-47 Ph 2- (OCH ₂ C (C ^) = CH ₂ ) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-48 Ph 2- (OCH ₂ ^s Bu) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-49 Ph 2- (OCH ₂ CN) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-50 Ph 2- (OCH (CH) OCH3) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-51 Ph 2- (CO2Et) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-52 Ph 2- (OAc) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-53 Ph 2- (OCH ₂ [2,2-Cl ₂ -3- 4-CF3 C3H6 pyridin-2 5-CF3
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TABLE 5 (Continued) At the. Cy ¹ (R ¹⁰ ) m (R ¹¹ ) n THE Cy ² (R ²¹ ) r (R ²⁰ ) p Ph- ^c Pr]) -il M-54 Ph 2- (OCH ₂ Ac) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-55 Ph 2- (OCH ₂ CH (OH) CH3) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-56 Ph 2- (OCH ₂ CH (OCH3) CH3) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-57 Ph 2- (The ^c Pen) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-58 Ph 2- (OCONH Pr) 4-CF3 C3H6 pyridin-2-il 5-CF3 [Tabe to 35]
TABLE 5 (Continued) At the. Cy ¹ <R '% (R ¹¹ ) n THE Cy ² (R ²¹ ) r (R ²⁰ ) p M-59 Ph 2- (OSO2CF3) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-60 Ph 2-Ph 4-CF3 C3H6 pyridin-2-il 5-CF3 M-61 Ph 2- (pyridin-3-yl) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-62 Ph 2- (Y ⁿ Pr) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-63 Ph 2- (CH ₂ CH = CH ₂ ) 4-CF3 C3H6 pyridin-2-il 5-CF3 M-64 Ph 2- (O ⁿ Pr) 4-Cl C3H6 pyridin-2-il 5-CF3 M-65 Ph 2- (O ⁿ Pr) 4-CF3 C4H ₈ pyridin-2-il 5-CF3 M-66 Ph 2- (OCH ₂ Pr) 4-Cl ch ₂ och ₂ pyridin-2-il 5-CF3 M-67 pyridin-2-il 5-CF3 C3H6 Ph 2- (OCH ₂ ⁱ Pr) 4-CF3 M-68 pyridin-2-il 5-CF3 C3H6 Ph 2- (OCH ₂ ^c Pr) 4-CF3 M-69 pyridin-2-il 5-CF3 C3H6 Ph 2- (CH ₂ OCH (OCH) CH3) 4-CF3 M-70 pyridin-2-il 5-CF3 C3H6 Ph 2- (CO ₂ Pr) 4-CF3
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TABLE 5 (Continued) At the. Cy ¹ (R ¹⁰ ) m (R ¹¹ ) n THE Cy ² (R ²¹ ) r (R ²⁰ ) p M-71 pyridin-2-il 5-CF3 CH2OCH2 Ph 2- (OCH ₂ ⁱ Pr) 4-CF3 M-72 pyridin-2-il 5-CF3 CH2OCH2 Ph 2- (OCH ₂ ^c Pr) 4-CF3 M-73 pyridin-2-il 5-CF3 CH2OCH2 Ph 2- (CH2OCH(OCH3) CH3) 4-CF3 M-74 pyridin-2-il 5-CF3 CH2OCH2 Ph 2- (CO2Pr) 4-CF3 M-75 Pyridazin-3-il _- 6-CF3 C3H6 Ph 2- (OCH ₂ ⁱ Pr) 4-CF3 [Tabe to 36]
TABLE 5 (Continued) At the. Cy ¹ (R ¹⁰ ) m (R ¹¹ ) _n THE Cy ² (R ²¹ ) r (R ²⁰ ) p M-76 Pyridazin -3-il 6-CF3 C3H6 Ph 2- (OCH ₂ ^c Pr) 4-CF3 M-77 Pyridazin -3-il 6-CF3 C3H6 Ph 2- (CH2OCH(OCH3) CH3) 4-CF3 M-78 Pyridazin-3-il 6-CF3 C3H6 Ph 2- (CO2 ⁱ Pr) 4-CF3 M-79 Pyridazin-3-il 6-CF3 CH2OCH2 Ph 2- (OCH ₂ ⁱ Pr) 4-CF3 M-80 Pyridazin-3-il 6-CF3 CH2OCH2 Ph 2- (OCH ₂ ^c Pr) 4-CF3 M-81 Pyridazin-3-il 6-CF3 CH2OCH2 Ph 2- (CH2OCH(OCH3) CH3) 4-CF3 M-82 Pyridazin-3-il 6-CF3 CH2OCH2 Ph 2- (CO2 ⁱ Pr) 4-CF3 M-83 Pyrazol-5-il 1- ⁿ Bu 3-CF3 C3H6 pyridin-2-il 5-CF3 M-84 pyrazol-5-il 1- (CH2CH(OCH3) 2) 3-CF3 C3H6 pyridin-2-il 5-CF3 M-85 pyrazol-5-il 1- ⁿ Pen 3-CF3 C3H6 pyridin-2-il 5-CF3 M-86 pyrazol-5-il 1- ⁿ Hex 3-CF3 C3H6 pyridin-2-il 5-CF3 M-87 pyrazol-5-il 1-Pr 3-CF3 C3H6 pyridin-2- 5-CF3
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TABLE 5 (Continued) At the. Cy ¹ (R ¹⁰ ) m (R ¹¹ ) n THE Cy ² (R ²¹ ) r (R ²⁰ ) pil M-88 pyrazol-5-il 1- (CH2CH = CH2) 3-CF3 C3H6 pyridin-2-il 5-CF3 M-89 pyrazol-5-il 1- (CH2CN) 3-CF3 C3H6 pyridin-2-il 5-CF3 M-90 pyrazol-5-il 1-Bn 3-CF3 C3H6 pyridin-2-il 5-CF3 M-91 pyrazol-5-il 1- (Pi ² -il) 3-CF3 C3H6 pyridin-2-il 5-CF3
Table 37
TABLE 5 (Continued) At the. Cy ¹ (R '% (R ¹¹ ) n THE Cy ² (R ²¹ ) r (R ²⁰ ) p M-92 pyrazol-5-il 1- _n Bu-3- (3,5- (CF3) 2- Ph) _- C3H6 pyridin-2-il 5-CF3 M-93 pyrazol-5-il 1- ⁿ Bu-3- (3,5-F ₂ -Ph) _- C3H6 pyridin-2-il 5-CF3 M-94 pyrazol-5-il 1- ⁿ Bu-3- (3,4,5-F ₃ - Ph) _- C3H6 pyridin-2-il 5-CF3 M-95 pyrazol-5-il HCH2OCH3) 3-CF3 C3H6 pyridin-2-il 5-CF3 M-96 pyrazol-5-il 1- (CH2OEt) 3-CF3 C3H6 pyridin-2-il 5-CF3 M-97 pyrazol-5-il HCH2CH2O CH3) 3-CF3 C3H6 pyridin-2-il 5-CF3 M-98 pyrazol-5-il HCH2CH2 OEt) 3-CF3 C3H6 pyridin-2-il 5-CF3 M-99 pyrazol-5-il 1- (CH2CH (OEt) 2) 3-CF3 C3H6 pyridin-2-il 5-CF3 M-100 pyrazol-5-il 1- (CH ₂ CH ₂ CH (OCH3) 2) 3-CF3 C3H6 pyridin-2-il 5-CF3 M-101 pyrazol-5-il HCH2CH2CH (OEt) 2) 3-CF3 C3H6 pyridin-2-il 5-CF3 M-102 pyrazol-5-il 1- (CH ₂ ([1,3] dioxo- 3-CF3 C3H6 pyridin-2-il 5-CF3
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lan-2-il)) M-103 pyrazol-5-il 1- (CH ₂ CH (OCH ₃ ) ₂ ) - 3- (3,5-F ₂ -Ph) C ₃ Hg pyridin-2-il 5-CF ₃
Chemical formula 38
[Table 38]
At the, Cy ' C8 ”) _o THE Cy ²(R ") _B N-1 Ph 2-COCHj'Pr) 4-CFj QA pyridin 2-il - 5-CF ₃ N-2 Ph 2-fOCH / Pr) 4-CF ₃ CjHj pyridin 2-il - 5-CF ₃ N-3 Ph 2-; CH _i OCH (OCH ₃ ) CHP 4-CF, pyridin 2-il - 5-CF ₃ N-4 Ph 2- (CO; Pr) 4-CF ₂ QsH, pyridin 2-il - 5-CF ₃ N-5 Ph 2; _ΟΟΗ: Ργ) 4-CF ₂ CH ₂ OCH ₂ pyridin 2-il - 5-CF ₃ N-6 Ph 2-ÍOCH, ⁵ Pr) 4-CF ₃ ch ₂ och ₂ pyridin 2-il - 5-CFj N-7 Ph 2-ÍCH ₂ OCH (OCH ₃ ) CH ₃ ) 4-CF ₂ ch ₂ och ₂ pyridin 2-il - 5-CF ₃ N-8 Ph 2-'COjPr) 4-CF ₃ ch ₂ och ₂ pyridin 2-il - 5-CF ₃ N-9 Ph 2-: OCH ₂ 'Pr; 4-CFj CsH, pindazin-3-il - 6-CF ₃ N-10 Ph 2-; OCH ₂ = Pr) 4-CF ₃ HERE pyridazin-3-il - 6-CF _s N-11 Ph 2-; ch ₂ och (och ₃ ) chj) 4-CF, ChH, pyridazin-3-il - 6-CF3 N-12 Ph 2-ÍCÜ.Pr) 4-CF ₃ C3H5 pyridazin-3-il - 6-CF ₃ N-13 Ph 2-; OCH ₂ 'Pri 4-CFj CHjOCH ₂ pyridazin-3-il - 6-CF ₃ N-14 Ph 2-; OCH _: = Pr) 4-CF ₃ CHjOCH ₂ pyridazin-3-il - 6-CF ₃ N-15 Ph 2-; ch ₂ och (ocHj) ch ₃ ) 4-CF ₃ CHjOCH ₂ pyridazin-3-il - 6-CF ₃
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108/134 [Table 39] TABLE 6 (Continued)
At the. Cy ' (R ’° X, (R), THE Cy ² (HR (R ³³ ), N-16 Ph 2- (CCb'Pr) 4-CF ₃ CHjOCI-t pyridazin-3-il - 6-CF ₃ N-17 pyridin 2-il - 5-CF ₃ CàHfe Ph 2-ÍOCI-VPr) 4-CF ₃ IM-18 pyridin 2-il - 5-CF ₃ cm Ph 2- (OCI-t ^and Pr) 4-CF ₃ N-19 pyridin 2-il - 5-CF ₃ HERE Ph 2- (CH _J OCrtOCH ₃ ) CI-l _i ) 4-CF ₃ N-20 pyridin 2-il - 5-CF ₃ here Ph 2- (Οθ / Ρτ) 4-CF ₃ N-21 pyridin 2-il - 5-CF ₃ ci-toci-t Ph 2- (0CI-yPr) 4-CF ₃ N-22 pyridin 2-il - 5-CF ₃ CHjOCH; Ph 2- (0CI-t ^Q Pr) 4-CF ₃ N-23 pyridin 2-il - 5-CF ₃ CHjOCHj Ph S-íd-ljCCHtCjCI-qJCI-lj) 4-CFj N-24 pyridin 2-il - 5-CF ₃ ChljOCH; Ph 2- (CCÇPr) 4-CF ₃ N-25 pyridazin-3-il - 6-CF ₃ CiHs Ph 2- (0CI-yPr) 4-CF ₃ N-26 pyridazin-3-il - 6-CF ₃ HERE Ph 24OCH, ^c Pr) 4-CF ₃ N-27 pyridazin-3-il - 6-CF ₃ CM Ph 2- (CHjOCKOCht3) CH3) 4-CF ₃ N-28 pyridazin-3-il - 6-CF ₃ HERE Ph 2-ÍCO / Pr) 4-CF ₃ N-29 pyridazin-3-il - 6-CF ₃ CHjCChl; Ph 2-ÍOCHjPr) 4-CFj N-30 pyridazin-3-il - 6-CF ₃ Cl-kOCI-k Ph 2- (CCI-fc ^c Pr) 4-CF ₃
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109/134 [Table 40] TABLE 6 (Continued)
At the. Cy Λ CR), THE ç/ CR ” _ir / nia ^uri / p N-31 pyridazin-3-il - 6-CFj CHjOCHí Ph a-iCHjOCHíocHjíCHj) 4-CFj N-32 pyridazin-3-il - 6-CFj CHjOCHj Ph 2-: COí’Pr) 4-CFj N-33 pyrazole-S-il 1-Bu 3-CFj CjH, pyridin 2-il - 5-CFj N-34 pyrazole-5-il 1- (CHjCH (OCH ₃ ) j) 3-CFj CjH, pyridin 2-il - 5-CFj N-35 pyrazole-5-il 1-Pen 3-CFj C ₃ H, pyridin 2-il - 5-CFj N-36 pyrazole-5-il l-Hex 3-CFj CjH, pyridin 2-il - 5-CFj N-37 pyrazole-5-il 1-'Pr 3-CFj CjH, pyridin 2-il - 5-CFj N-3S pyrazole-5-íl 1-CHI ₂ CH = CH ₂ ) 3-CFj CjH ₄ pyridin 2-il - 5-CFj N-39 pyrazole-5-il 1- (CHiCN) 3-CF ₃ CjHj pyridin 2-il - 5-CFj N-40 pyrazole-5-il 1-Bn 3-CF ₃ CjH, pyridin 2-il - 5-CFj N-41 pyrazole-5-il 1- (Py-2-yl) 3-CF ₃ C ₃ H, pyridin 2-il - 5-CFj N-42 pyrazole-5-il 1-nBu 3- (3.5- (CFj) ₂ -Rh) - CjH, pyridin 2-il - 5-CFj N-43 pyrazole-5-íl 1- ⁿ Bu 3- (3.5-F ₃ -Ph) - HERE pyridin 2-il - 5-CFj N-44 pyrazole-5-il 1- ^r Bu 3- <3.4.5-F ₃ -Ph) - CjH ₄ pyridin 2-il - 5-CFj N-45 pyrazole-5-il I- (CHiOCHj) 3-CF ₃ CjH, pyridin 2-il - 5-CFj
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110/134 [Table 41]
TABLE 6 (Continued)
At the. Cy ' I Q/ rt THE Cy ¹π N-46 pyrazole-5-il 1- (CH; OEt) 3-CF ₃ CjH, pyridin 2-il - 5-CF, N-47 pyrazole-5-il I-CCHjCH ^ OCHj) 3-CFj CjH, pyridin 2-il - 5-CFj N-48 pyrazole-E-il 1- (CH; CHjOEt) 3-CF ₃ CjHj pyridin 2-il - 5-CFj N-49 pyrazole-5-ÍI l-tCHjCHÍOEtíí) 3-CF ₃ C} H _f pyridin 2-il - 5-CFj N-50 pyrazole-5-il 1 - (CHjCHjCH (OCHj) j) 3-CF ₃ CjHj pyridin 2-il - 5-CFj N-51 pyrazole-Sil 1-CCHíCH ^ HÍOEtíi) 3-CF ₃ C, H, pyridin 2-il - 5-CFj N-52 pyrazole-5-il 1-ÍCHí ([1.3] (fexo! Art-2-il » 3-CFj CjH, pyridin 2-il - 5-CFj N-53 pyrazole-5-il 1- (CH ₂ CH (OCH3) ₂ ) 3- (3.5-F ₂ -Ph) - C, H, pyridin 2-il - 5-CFj
[00216] The physical constants of some of the compounds shown in TABLES 1 to 6 are shown below. Additionally, "vis" means "viscous oil".
[00217] Compound H-1: vis; ¹ H-NMR (CDCI ₃ , δ ppm, measurement temperature 25Ό) 8.49 (s, 1H), 7.90-7.86 (m, 1H), 7.39 (d, 0.8H), 7 , 26 (d, 0.2H), 7.15 (d, 1H), 7.08 (s, 1H), 6.91 (d, 1H), 4.91 - 4.89 (m, 0.8H ), 4.65 (m, 0.2H), 3.78 (d, 2H), 3.59 (brs, 2H), 2.76-2.30 (m, 3H), 2.162.04 (m, 3H), 1.83-1.67 (m, 4H), 1.41-1.37 (m, 1H), 1.07 (d-similar, 6H). [00218] Additionally, it is evaluated that Compound H-1 is a mixture of two compounds that are conformational isomers and represented by the following formulas. One of the compounds is a compound in which the distance between position 7 of methylene and position 9 of pyridyloxy on the 9-azabicyclo ring [3.3.1] nonane is smaller and the other is a compound in which the distance between position 7 of methylene and the 9-position of pyridyloxy on the 9-azabicyclo ring [3.3.1] nonane is greater.
Chemical formula 39
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W ^ cf ₃

(Hl) [00219] Compound H-2: vis; ¹ H-NMR (CDCI ₃ , δ ppm, measuring temperature 20.2Ό) 8.49 (s, 1H), 7.88 (dd, 1H), 7.39 (d, 1 H), 7.17 ( d, 1H),
7.08 (s, 1H), 6.95 (d, 1H), 5.00-4.92 (m, 0.8H), 4.67 (m, 0.2H), 3.87 (d, 2H), 3.59 (brs, 2H), 2.75-2.41 (m, 3H), 2.14-2.05 (m, 2H), 1.83-1.71 (m, 3H) , 1.43-1.24 (m, 3H), 0.66-0.60 (m, 2H), 0.39-0.35 (m, 2H).
[00220] Compound H-5: vis; ¹ H-NMR (CDCI ₃ , δ ppm, measurement temperature: 22.7Ό) 7.77 (d, 1H), 7.68 (d, 1H), 7.17 (d, 1H), 7.08 ( s, 1H), 6.91 (d, 1H), 4.95-4.90 (m, 0.7H), 4.63 (m, 0.3H), 3.78 (d, 2H), 3 , 62 (brs, 2H), 2.80-2.43 (m, 2H), 2.19-2.03 (m, 2H), 1.85-1.75 (m, 2H), 1,411.37 (m, 1H), 1.05 (d, 6H).
[00221] Compound H-41: vis; ¹ H-NMR (CDCI ₃ , δ ppm, measurement temperature: 20.7Ό) 8.53 (d, 1H), 7.90 (dd, 1H), 7.40 (d, 1H), 7.16 (d , 1H), 7.08 (s, 1H), 6.90 (s, 1H), 4.90-4.85 (m, 0.7H), 4.60 (m, 0.3H), 3, 78 (d, 2H), 3.58 (brs, 2H), 2.74-2.40 (m, 3H), 2.18-2.05 (m, 3H), 1,821.72 (m, 3H) , 1.41-1.34 (m, 2H), 1.06 (d, 6H).
[00222] Compound H-42: vis; ¹ H-NMR (CDCI ₃ , δ ppm, measurement temperature: 22.3Ό) 8.49 (s, 1H), 7.88 (dd, 1H), 7.39 (d, 1H), 7.17 ( d, 1H),
7.09 (s, 1H), 6.95 (d, 1H), 4.98-4.94 (m, 0.8H), 4.60 (m, 0.2H), 4.10 (q,
2H), 3.59 (brs, 2H), 2.74-2.40 (m, 3H), 2.11-2.05 (m, 2H), 1.81-1.69 (m,
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3H), 1.49-1.37 (m, 5H).
[00223] Compound H-43: vis; ¹ H-NMR (CDCl ₃ , δ ppm, measurement temperature: 21.3 ° C) 8.49 (s, 1H), 7.87 (dd, 1H), 7.39 (d, 1H), 7, 17 (d, 1H), 7.09 (s, 1H), 6.92 (d, 1H), 4.95-4.90 (m, 0.9H), 4.60 (m, 0.1H) , 3.98 (t, 2H), 3.59 (brs, 2H), 2.75-2.40 (m, 3H), 2.14-2.04 (m, 2H), 1.89-1 , 69 (m, 6H), 1.41-1.36 (m, 1H), 1.08 (t, 3H) [00224] Compound K-8: vis; ¹ H-NMR (CDCl ₃ , δ ppm, measuring temperature: 21.0 ° C) 8.44 (d, 1H), 8.04 (d, 1H), 7.79-7.63 (m, 3H ), 6.81 (d, 1H), 5.78 (m, 0.7H), 5.50 (m, 0.3H), 5.32-5.24 (m, 1H), 3.57 ( brs, 2H),
2.78-2.68 (m, 2H), 2.42-1.90 (m, 4H), 1.77-1.60 (m, 2H), 1.45-1.26 (m, 8H).
[00225] Compound K-12: vis; ¹ H-NMR (CDCl3, δ ppm, measurement temperature: 20.8 ° C) 8.43 (s, 1H), 8.07 (d, 1H), 7.76 (dd, 1H), 7.68 (d, 1H), 7.26 (s, 1H), 6.84 (d, 1H), 5.69-5.64 (m, 0.7H), 5.51 (m, 0.3H), 5.335,24 (m, 1H), 4.47 (d, 0.5H), 4.00 (dd, 3.5H), 3.54-3.27 (d, d, d, 2H), 2.852, 68 (m, 2H), 2.27 (d, 0.3H), 1.91 (d, 1.7H), 1.41 (d, 6H) [00226] Compound H-51: vis; ¹ H-NMR (CDCl3, δ ppm, measurement temperature: 21.2 ° C) 8.49 (s, 1H), 7.88 (dd, 1H), 7.40-7.35 (d, d, total 2H), 7.26 (s, 1H), 6.98 (d, 1H), 5.22 (s, 2H), 5.06-5.01 (m, 1H), 3.62 (brs, 2H), 3.53 (s, 3H), 2.75-2.65 (m, 2H), 2.50-2.39 (m, 1H), 2.14-2.04 (m, 2H) ,
1.79- 1.67 (m, 3H), 1.45-1.33 (m, 2H) [00227] Compound H-52: melting point [107-110 ° C] [00228] Compound H-53: point melting [141-144 ° C] [00229] Compound H-54: vis; ¹ H-NMR (CDCl3, δ ppm, measurement temperature: 21.3 ° C) 8.49 (s, 1H), 7.88 (dd, 1H), 7.39 (d, 1H), 7.17 (d, H), 7.08 (s, 1H), 6.92 (d, 1H), 4.93-4.91 (m, 1H), 4.01 (t, 2H), 3.59 ( brs, 2H), 2.74-2.40 (m, 3H), 2.14-2.05 (m, 2H), 1.86-1.74 (m, 5H), 1.70-1, 49 (m, 2H), 1.41-1.39 (m, 2H), 1.01 (t, 3H) [00230] Compound H-55: vis; ¹ H-NMR (CDCl3, δ ppm, measurement temperature: 21.3 ° C) 8.50 (s, 1H), 7.88 (dd, 1H), 7.80 (s, 1H), 7.58 (d,
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1H), 7.36 (d, 1H), 6.99 (d, 1H), 6.16 (s, 1H), 5.12-5.09 (m, 1H), 4,194.01 (m, 4H ), 3.64 (brs, 2H), 2.77-2.03 (m, 3H), 1.80-1.66 (m, 3H), 1,471.35 (m, 2H) [00231] Compound H -56: ¹ H-NMR (CDCl ₃ , δ ppm, measurement temperature: 22.1 ° C) 8.51 (s, 1H), 7.89 (dd, 1H), 7.71 (s, 1H) , 7.49 (d, 1H), 7.38 (d, 1H), 6.92 (d, 1H), 5.08-5.04 (m, 1H), 4.57 (s, 2H), 3.77-3.67 (m, brs, total 3H), 2.79-2.69 (m, 2H), 2.44-2.02 (m, 3H), 1.80-1.59 ( m, 3H),
1.48- 1.44 (m, 2H), 1.25 (d, 6H) [00232] Compound H-57: vis; ¹ H-NMR (CDCl3, δ PPM, measurement temperature: 21.3 ° C) 8.50 (s, 1H), 7.88 (dd, 1H), 7.66 (s, 1H), 7.51 (d, 1H), 7.39 (d, 1H), 6.93 (d, 1H), 5.07-5.03 (m, 1H), 4.52 (s, 2H), 3.65 ( brs, 2H), 3.50 (s, 3H), 2.79-2.68 (m, 2H), 2.40-2.02 (m, 3H), 1.80-1.61 (m, 3H), 1.40-1.30 (m, 2H) [00233] Compound H-58: vis; ¹ H-NMR (CDCl ₃ , δ ppm, measurement temperature: 21.3 ° C) 8.50 (s, 1H), 7.88 (d, 1H), 7.69 (s, 1H), 7, 50 (d, 1H), 7.38 (d, 1H), 6.93 (d, 1H), 5.04 (m, 1H), 4.57 (s, 2H), 3.66-3.58 (brs, q, total 4H), 2.78-2.68 (m, 2H), 2.40-2.04 (m, 3H), 1.79-1.60 (m, 3H), 1.401, 33 (m, 2H), 1.26 (t, 3H) [00234] Compound H-59: vis; ¹ H-NMR (CDCl3, δ ppm, measuring temperature: 21.3 ° C) 8.50 (s, 1H), 7.88 (dd, 1H), 7.36 (s, 1H), 6.87 (d, 1H), 6.78 (s, 1H), 6.74 (d, 1H), 5.05-5.01 (m, 1H), 4.41 (brt, 1H), 3.64 ( brs, 2H), 2.98 (t, 2H), 2.80-2.70 (m, 2H), 2.44-1.90 (m, 4H), 1.80-1.65 (m, 3H),
1.49- 1.43 (m, 2H), 1.01 (d, 6H) [00235] Compound H-60: vis; ¹ H-NMR (CDCl3, δ ppm, measurement temperature: 21.2 ° C) 8.49 (s, 1H), 7.87 (dd, 1H), 7.39 (d, 1H), 7.18 (d, 1H), 7.13 (s, 1H), 6.94 (d, 1H), 4.97-4.92 (m, 1H), 4.59-4.50 (m, 1H), 3.59 (brs, 2H), 2.74-2.41 (m, 3H), 2.14-2.05 (m, 2H), 1.81-1.69 (m, 3H), 1, 42-1.35 (m, d, total 8H) [00236] Compound H-61: vis; ¹ H-NMR (CDCl3, δ ppm, measurement temperature: 21.7 ° C) 8.49 (s, 1H), 7.87 (dd, 1H), 7.38 (d, 1H), 7.16 (d,
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1H), 7.10 (d, 1H), 6.93 (d, 1H), 4.95-4.91 (m, 1H), 4.36-4.30 (m, 1H), 3.58 (brs, 2H), 2.74-2.40 (m, 3H), 2.13-2.04 (m, 2H), 1.81-1.56 (m, 5H), 1.41-1 , 33 (m, 2H), 1.31 (d, 3H), 1.00 (t, 3H) [00237] Compound H-62: vis; ¹ H-NMR (CDCl ₃ , δ ppm, measurement temperature: 21.6 ° C) 8.49 (s, 1H), 7.88 (dd, 1H), 7.48 (d, 1H), 7, 40 (d, 1H), 7.36 (s, 1H), 7.06 (d, 1H), 5.09-5.06 (m, 1H), 5.01-4.93 (m, 1H) , 3.62 (brs, 2H), 2.76-2.66 (m, 2H), 2.40-2.05 (m, 3H), 1.77-1.61 (m, 3H), 1 , 38 (d, 6H), 1.45-1.33 (m, 2H) [00238] Compound H-63: vis; ¹ H-NMR (CDCl3, δ ppm, measurement temperature: 19.7 ° C) 8.50 (s, 1H), 7.89 (d, 1H), 7.46 (d, 1H), 7.41 -7.38 (d, s, total 2H), 7.19-7.02 (m, 1H), 5.11-5.04 (m, 1H), 4.45 (d, 1H), 3, 63 (brs, 2H), 2.76-2.66 (m, 2H), 2.44-2.20 (m, 1H), 2.11-2.05 (m, 2H), 1.801.63 ( m, 3H), 1.49-1.44 (m, 2H) [00239] Compound H-64: vis; ¹ H-NMR (CDCl3, δ ppm, measurement temperature: 22.2 ° C) 8.49 (s, 1H), 7.88 (dd, 1H), 7.38 (d, 1H), 7.20 (d, 1H), 7.10 (s, 1H), 6.96 (d, 1H), 6.11-6.02 (m, 1H), 5.49-5.28 (m, 2H), 5.00-4.99 (m, 1H), 4.60 (d, 2H), 3.61 (brs, 2H), 2.75-2.30 (m, 3H), 1.821.69 (m, 3H), 1.45-1.35 (m, 2H) [00240] Compound H-65: vis; ¹ H-NMR (CDCl ₃ , δ ppm, measurement temperature: 22.0 ° C) 8.49 (s, 1H), 7.87 (d, 1H), 7.38 (d, 1H), 7, 17 (d, 1H), 7.10 (s, 1H), 6.96 (d, 1H), 5.47 (t, 2H), 5.01-4.95 (m, 1H), 4.58 (d, 2H), 3.59 (brs, 2H), 2.73-2.40 (m, 3H), 2.14-2.02 (m, 2H), 1.77 (d, 6H), 1,791.68 (m, 3H), 1.41-1.37 (m, 2H) [00241] Compound H-66: vis; ¹ H-NMR (CDCl3, δ ppm, measurement temperature: 21.7 ° C) 8.49 (s, 1H), 7.88 (dd, 1H), 7.39 (d, 1H), 7.16 (d, 1H), 7.07 (s, 1H), 6.88 (d, 1H), 4.87-4.82 (m, 1H), 3.65 (s, 2H), 3.58 ( brs, 2H), 2.78-2.63 (m, 2H), 2.50-2.41 (m, 1H9, 2.17-2.05 (m, 2H), 1,821.71 (m, 3H ), 1.43-1.36 (m, 2H), 1.08 (s, 9H) [00242] Compound H-67: vis; ¹ H-NMR (CDCl3, δ ppm, measurement temperature: 21.7 ° C) 8.49 (s, 1H), 7.88 (dd, 1H), 7.38 (d, 1H), 7.24 (d,
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1H), 7.11 (s, 1H), 6.97 (d, 1H), 6.18 (t, 1H), 5.08-5.00 (m, 1H), 4.72 (d, 2H ), 3.62 (brs, 2H), 2.74-2.64 (m, 2H), 2.49-2.36 (m, 1H), 2.15-2.04 (m, 2H), 1.80-1.66 (m, 3H), 1.45-1.33 (m, 2H) [00243] Compound H-68: vis; ¹ H-NMR (CDCl ₃ , δ ppm, measurement temperature: 21.7 ° C) 8.49 (s, 1H), 7.87 (dd, 1H), 7.38 (d, 1H), 7.277, 25 (d, s, total 2H), 6.98 (d, 1H), 5.09-5.01 (m, 1H), 4.77 (s, 2H), 3.63 (brs, 2H), 2.74-2.59 (m, 2H), 2.54 (s, 1H), 2.53-2.35 (m, 1H), 2,132.01 (m, 2H), 1.81-1, 67 (m, 3H), 1.45-1.33 (m, 2H) [00244] Compound H-69: vis; ¹ H-NMR (CDCl ₃ , δ ppm, measurement temperature: 21.9 ° C) 8.49 (s, 1H), 7.87 (dd, 1H), 7.38 (d, 1H), 7, 17 (d, 1H), 7.10 (s, 1H), 6.93 (d, 1H), 5.14 (s, 1H), 5.00 (s, 1H), 4.98-4.93 (m, 1H), 4.48 (s, 2H), 3.59 (brs, 2H), 2.76-2.40 (m, 3H), 2.15-2.03 (m, 2H), 1.85 (s, 3H), 1.80-1.70 (m, 3H), 1.43-1.34 (m, 2H) [00245] Compound H-70: vis; ¹ H-NMR (CDCl3, δ ppm, measurement temperature: 21.5 ° C) 8.49 (s, 1H), 7.88 (dd, 1H), 7.38 (d, 1H), 7.16 (d, 1H), 7.07 (s, 1H), 6.90 (d, 1H), 4.90-4.88 (m, 1H), 3.89-3.77 (m, 2H), 3.59 (brs, 2H), 2.76-2.30 (m, 3H), 2.20-2.05 (m, 2H), 1.92-1.55 (m, 6H), 1, 40-1.26 (m, 2H), 1.06 (d, 3H), 0.97 (t, 3H) [00246] Compound H-71: vis; ¹ H-NMR (CDCl3, δ ppm, measuring temperature: 21.8 ° C) 8.50 (s, 1H), 7.89 (dd, 1H), 7.38 (d, 1H), 7.30 (s, 1H), 7.06 (d, 1H), 5.17-5.13 (m, 1H), 4.86 (s, 2H), 3.68 (brs, 2H), 2,772.66 ( m, 2H), 2.46-2.02 (m, 3H), 1.80-1.62 (m, 3H), 1.50-1.45 (m, 2H) [00247] Compound H-72 : ¹ H-NMR (CDCl3, δ ppm, measurement temperature: 21.1 ° C) 8.49 (s, 1H), 7.88 (dd, 1H), 7.39 (d, 1H), 7, 32 (s, 1H), 7.25 (d, 1H), 6.98 (d, 1H), 5.33 (q, 1H), 5.04-5.02 (m, 1H), 3.63 (brs, 2H), 3.44 (s, 3H), 2.76-2.65 (m, 2H), 2.50-2.40 (m, 1H), 2.17-2.07 (m , 2H),
1.80-1.68 (m, 3H), 1.53 (d, 3H), 1.50-1.30 (m, 2H) [00248] Compound H-73: melting point [87-89 ° C] [00249] Compound H-74: melting point [93-97 ° C] [00250] Compound H-75: melting point [102-105 ° C]
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116/134 [00251] Compound H-76: melting point [114-117 ° C] [00252] Compound H-77: ¹ H-NMR (CDCl ₃ , δ ppm, measurement temperature: 21.3 * 0) 8.50 (s, 1H), 7.88 (dd, 1H), 7.48 (d, 1H), 7.37 (d, 1H),
7.32 (s, 1H), 7.04 (d, 1H), 5.30-5.01 (m, 1H), 3.62 (brs, 2H), 2.77-2.67 (m,
2H), 2.46-2.10 (m, 3H), 2.26 (s, 3H), 1.77-1.41 (m, 5H) [00253] Compound H-78: ¹ H-NMR ( CDCl3, δ ppm, measuring temperature: 21.2 ° C) 8.48 (s, 1H), 7.86 (dd, 1H), 7.38-7, 23 (m, 8H), 6.97 ( d, 1H), 4.99-4.95 (m, 1H), 4.50 (q, 1H), 4.37 (d, 2H), 3.56 (brs, 2H), 2.73 (d , 1H), 2.73-2.64 (m, 2H), 2.54-2.47 (m, 1H), 2.09-1.99 (m, 2H), 1.741.68 (m, 3H ), 1.47-1.35 (m, 2H) [00254] Compound H-79: ¹ H-NMR (CDCl3, δ ppm, measurement temperature: 21.8 ° C) 8.50 (s, 1H) , 7.88 (dd, 1H), 7.39 (d, 1H), 7.28 (d, 1H), 7.04 (s, 1H), 6.98 (d, 1H), 5.07- 5.04 (m, 1H), 4.57 (s, 2H), 3.60 (brs, 2H), 2.78-2.35 (m, 3H), 2.35 (s, 3H), 2 , 27-2.07 (m, 2H), 1.79-1.61 (m, 3H), 1.58-1.40 (m, 2H) [00255] Compound H-80: ¹ H-NMR ( CDCl3, δ ppm, measurement temperature: 21.4 ° C) 8.49 (s, 1H), 7.88 (dd, 1H), 7.39 (d, 1H), 7.21 (d, 1H) , 7.14 (s, 1H), 6.97 (d, 1H), 5.14-5.10 (m, 1H), 4.23-4.19 (m, 1H), 4.094.03 (m , 1H), 3.87-3.82 (m, 1H), 3.63 (brs, 2H), 2.96 (d, 1H), 2.75-2.41 (m, 3H), 2, 13-2.06 (m, 2H), 1.79-1.60 (m, 3H), 1.4 [00256] Compound H-81: ¹ H-NMR (CDCl3, δ ppm, temper measuring range: 22.0 ° C) 8.49 (s, 1H), 7.88 (dd, 1H), 7.38 (d, 1H), 7.18 (d, 1H), 7.10 ( s, 1H), 6.92 (d, 1H), 4.95-4.93 (m, 1H), 4.04-4.01 (m, 1H), 3,943.89 (m, 1H), 3 , 78-3.73 (m, 1H), 3.60 (brs, 2H), 3.46 (s, 3H), 2.76-2.50 (m, 3H), 2.11-2.04 (m, 2H), 1.80-1.68 (m, 3H), 1.4 [00257] Compound H-82: ¹ H-NMR (CDCl3, δ ppm, measurement temperature: 21.7 ° C) 8.49 (s, 1H), 7.87 (dd, 1H), 7.38 (d, 1H), 7.15 (d, 1H), 7.13 (s, 1H), 6.92 (d , 1H), 4.90-4.84 (m, 1H), 4.83-4.79 (m, 1H), 3.58 (brs, 2H), 2.74-2.60 (m, 2H ), 2.41 - 2.08 (m, 3H), 1.91 - 1.63 (m, 11H), 1.381.34 (m, 2H)
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117/134 [00258] Compound H-83: ¹ H-NMR (CDCl ₃ , δ ppm, measurement temperature: 21.2 ° C) 8.49 (s, 1H), 7.87 (dd, 1H), 7.44 (d, 1H), 7.38-7.36 (m,
2H), 7.03 (d, 1H), 5.07 (m, 1H), 4.95 (d, 1H), 3.92-3.86 (m, 1H), 3.62 (brs,
2H), 2.75-2.65 (m, 2H), 2.44-2.01 (m, 3H), 1.77-1.61 (m, 3H), 1,431.34 (m, 2H) , 1.30 (d, 6H) [00259] Compound H-84: melting point [127-130 ° C] [00260] Compound H-85: ¹ H-NMR (CDCl ₃ , δ ppm, measurement temperature: 23.3 ° C) 8.48 (s, 1H), 7.86 (dd, 1H), 7.58-7, 52 (m, 4H), 7,497.33 (m, 4H), 7.03 ( d, 1H), 5.02 (m, 1H), 3.53 (brs, 2H), 2.71-2.61 (m, 2H), 2.25-1.89 (m, 3H), 1 , 62-1.51 (m, 3H), 1.50-1.40 (m, 2H), [00261] Compound H-86: ¹ H-NMR (CDCl3, δ ppm, measurement temperature: 23.1 ° C) 8.79 (s, 1H), 8.59 (t, 1H), 8.49 (s, 1H), 7.89-7.81 (m, 1H), 7.65-7.57 (dd, s, total 2H), 7.38-7.34 (m, 2H), 7.09 (d, 1H), 5.11 (m, 1H), 3.56 (brs, 2H), 2 , 74-2.64 (m, 2H), 2.25-1.90 (m, 3H), 1.70-1.54 (m, 3H), 1.26-1.00 (m, 2H) , [00262] Compound H-87: ¹ H-NMR (CDCl3, δ ppm, measurement temperature: 21.8 ° C) 8.50 (s, 1H), 7.89 (dd, 1H), 7.41 -7, 36 (d, d, s, total 3H), 6.90 (d, 1H), 5.07-5.05 (m, 1H), 3.64 (brs, 2H), 2.87 ( t, 2H), 2.75-2.68 (m, 2H), 2.45-2.08 (m, 3H), 1.83-1.42 (m, 7H), 1.08 (t, 3H) [00263] Compound H-88: ¹ H-NMR (CDCl3, δ ppm, temperature measuring a: 22.0 ° C) 8.33 (s, 1H), 7.74 (dd, 1H), 7.58 (d, 1H), 7.47 (s, 1H), 7.32 ( d, 1H), 7.18 (d, 1H), 5.80-5.66 (m, 1H), 5.30-5.05 (m, 3H), 3.68 (brs, 2H), 2 , 97-2.85 (m, 2H), 2.77-2.39 (m, 2H), 2.39-2.00 (m, 3H), 1,791.26 (m, 5H) [00264] Compound H-89: ¹ H-NMR (CDCl3, δ ppm, measurement temperature: 23.5 ° C) 8.48 (s, 1H), 7.87 (dd, 1H), 7.37 (d, 1H) , 6.91-6.83 (m, 3H), 4.82-4.77 (m, 1H), 3.94 (t, 2H), 3.57 (brs, 2H), 2.69-2 , 30 (m, 3H), 2.12-2.04 (m, 2H), 1.89-1.60 (m, 5H), 1.41-1.32 (m, 2H), 1.07 (t, 3H) [00265] Compound H-90: ¹ H-NMR (CDCl3, δ ppm, measurement temperature: 20.8 ° C) 8.49 (s, 1H), 7.91 (dd, 1H) , 7.48 (d, 1H), 7.17 (d, 1H),
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7.08 (s, 1H), 6.99 (d, 1H), 5.02-4.98 (m, 1H), 3.98 (t, 2H), 3.60-3.58 (m, 2H), 2.58-2.49 (m, 2H), 2.30-2.20 (m, 2H), 1.91-1.75 (m, 7H), 1.07 (t, 3H) [00266] Compound H-29: ¹ H-NMR (CDCl ₃ , δ ppm, measurement temperature: 20.4 ° C) 8.50 (s, 1H), 7.89 (dd, 1H), 7.38 (d, 1H), 7.16 (d, 1H), 7.09 (s, 1H), 7.03 (d, 1H), 4.97-4.95 (m, 1H), 3.97 ( q, 4H), 3.79 (d, 2H), 3.58-3.33 (ddd, 2H), 2.74-2.65 (m, 2H), 2.19-2.12 (m, 1H), 1.98 (brd, 2H), 1.06 (d, 6H) [00267] Compound J-42: melting point [170-172 ° C] [00268] Compound K-38: ¹ H-NMR (CDCl3, δ ppm, measurement temperature: 21.5 ° C) 8.49 (s, 1H), 7.88 (dd, 1H), 7.39 (d, 1H), 7.19 (d, 1H ), 7.07 (d, 1H), 4.98-4.93 (m, 1H), 4.34 (t, 2H), 3.60 (brs, 2H), 2.75-2.30 ( m, 3H), 2.14-2.07 (m, 2H), 1.86-1.67 (m, 5H), 1.44-1.38 (m, 2H), 1.04 (t, 3H) [00269] Compound K-39: ¹ H-NMR (CDCl3, δ ppm, measurement temperature: 22.3 ° C) 8.51 (s, 1H), 7.90 (dd, 1H), 7, 38 (d, 1H), 5.78 (s, 1H), 5.10-4.80 (m, 1H), 4.00 (t, 2H), 3.66 (brs, 2H), 2.75 -1.20 (m, 14H), 0.97 (t, 3H) [00270] Compound N-1: ¹ H-NMR (CDCl ₃ , δ ppm, measuring temperature: 20.8 ° C) 8.64 (s, 1H), 7.85-7.81 (m, 1H), 7.74-7.69 (m, 1H), 7.17 (d , 1H), 7.08 (s, 1H), 6.92 (d, 1H), 4.69 (m, 1H), 3.80 (d, 2H),
3.36 (brs, 2H), 2.61-2.56 (m, 2H), 2.17-2.05 (m, 3H), 1.91-1.86 (m, 1H), 1, 65-1.53 (m, 3H), 1.27-1.26 (m, 2H), 1.08 (d, 6H) [00271] Compound H-92: ¹ H-NMR (CDCl ₃ , δ ppm , measuring temperature: 21.3 ° C) 8.50 (s, 1H), 7.88 (d, 1H), 7.37 (d, 1H), 7.31 (d, 1H), 6.84 (d, 1H), 5.11-5.07 (m, 0.8H), 4.75 (m, 0.2H), 3.88 (s, 3H), 3.66 (brs, 2H), 2.77-2.67 (m, 4H), 2.50-2.25 (m, 1H), 2.13-2.04 (m, 3H),
1.80-1.48 (m, 6H), 1.02 (t, 3H) [00272] Compound H-93: ¹ H-NMR (CDCl3, δ ppm, measurement temperature: 20.2 ° C) 8 , 49 (s, 1H), 7.87 (dd, 1H), 7.38 (d, 1H), 7.05 (d, 1H),
6.85 (d, 1H), 5.20-4.80 (m, 2H), 3.61 (brs, 2H), 3.52-3.44 (m, 1H), 3.012.90 (m, 1H), 2.70-2.33 (m, 3H), 2.10-2.01 (m, 3H), 1.79-1.55 (m, 4H),
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1.48 (d, 3H) [00273] Now, examples of the hydroxylamine compound suitable for use as a production intermediate for cyclic amine compounds of the present invention are shown in Tables 15 to 20. In addition, these hydroxylamine compounds are substances formed in intermediate stages of a method similar to the production methods shown in the Examples mentioned above.
[00274] In TABLE 7, (R ¹⁰ ) m, (R ¹¹ ) n θ A represent the substituents on the hydroxylamine compound represented in the formula (llld). [00275] In TABLE 8, (R ¹⁰ ) m, (R ¹¹ ) n θ A represent the substituents on the hydroxylamine compound represented in the formula (IIIr). Chemical formula 40
ÍR ¹⁰ ) my (R) n> y ¹
OH fTable 42]
TABLE 7
At the Cy ¹ ir ¹⁰ ) _m GO)" THE e-1 Ph 2- (OCH ₂ Pr) 4-CF ₃ CjH = e-2 Ph 2-ÍOCH / Pr) 4-CF ₃ CjH _and e-3 Ph 2- _(t OCHíOCH CH,) CH _j) 4-CF ₃ CjHí e-4 Ph 2-; COz'Pr) 4-CF ₃ CjH, e-5 Ph 2- (OCH ₂ Pr) 4-CF ₃ CH ₂ OCH ₂ e-6 Ph 2-ÍOCH / Pr) 4-CF ₃ ch ₂ och ₂ e-7 Ph OCHÍOCH-2 CCH _{2:) CH3)} 4-CF ₃ ch ₂ och ₂ e-8 Ph 2- (CO / Pr) 4-CF ₃ CHjOCHj e-9 Ph 2-I ^r Pr) 4-CF ₃ CjH. _: e-11 pyridin -2- il - 5-CF ₃ c _} h ₅ e-12 pyridin -2- il - 5-CF ₃ ch ₂ och ₂ e-13 Ph 2- (CO ₂ CHj) 4-CF ₃ c ₃ h _: e-14 Ph 2-; OCHíOCH ₃ ) 4-CF ₃ c ₃ h. _: e-15 Ph 2-IOCHzPr) 4-CF ₃ CHjOCH ₂ e-16 Ph 2- (OCH ₂ Pr) 4-CF3 C ₃ H _e e-1 7 piridin - 3-il 2- (O ^r 'Pr) 6-CF ₃ CjH _: e-18 pyrazol-5-yl 1 -CBu) 3-CF ₃ CjH,
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TABLE 7 (Continued) At the. Cy ¹ (R '") m (R) n THE e-20 Ph 2- (OEt) 4-CF3 C3H6 e-22 Ph 2-OH 4-CF3 C3H6 e-23 Ph 2- (O ⁿ Bu) 4-CF3 C3H6 e-24 Ph 2 - ([1,3] dioxolan-2-yl) 4-CF3 C3H6 e-25 Ph 2- (CH ₂ O ⁱ Pr) 4-CF3 C3H6 e-26 Ph 2- (CH2OCH3) 4-CF3 C3H6 e-27 Ph 2- (CH2OEt) 4-CF3 C3H6 e-28 Ph 2- (NHCH ₂ 'Pr) 4-CF3 C3H6 e-29 Ph 2- (O'Pr) 4-CF3 C3H6 e-30 Ph 2- (O ^s Bu) 4-CF3 C3H6 e-31 Ph 2- (OCO2'Pr) 4-CF3 C3H6 e-32 Ph 2- (OCH2CF3) 4-CF3 C3H6 e-33 Ph 2- (OCH2CH = CH2) 4-CF3 C3H6 e-34 Ph 2- (OCH2CH = C (CH3) 2) 4-CF3 C3H6 e-35 Ph 2- (OCH ₂ ^t Bu) 4-CF3 C3H6 e-36 Ph 2- (OCH2CH = CCl2) 4-CF3 C3H6 e-37 Ph 2- (OCHCECH) 4-CF3 C3H6 e-38 Ph 2- (OCH2C (CH3) = CH2) 4-CF3 C3H6 e-39 Ph 2- (OCH ₂ ^s Bu) 4-CF3 C3H6 e-40 Ph 2- (OCH2CN) 4-CF3 C3H6 e-41 Ph 2- (OCH (CH3) OCH3) 4-CF3 C3H6 e-42 Ph 2- (CO2Et) 4-CF3 C3H6 e-43 Ph 2- (OAc) 4-CF3 C3H6 e-44 Ph 2- (OCH ₂ [2,2-Cl ₂ -3-Ph- ^c Pr]) 4-CF3 C3H6 e-45 Ph 2- (OCH2Ac) 4-CF3 C3H6 e-46 Ph 2- (OCH2CH (OH) CH3) 4-CF3 C3H6
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TABLE 7 (Continued) e-47 Ph 2- (OCH2CH (OCH3) CH) 4-CF3 C3H6
[Table 44]
TABLE 7 (Continued) At the. Cy ¹ (R ¹⁰ ) m (R ¹¹ ) n THE e-48 Ph 2- (The ^c Pen) 4-CF3 C3H6 e-49 Ph 2- (OCONH 'Pr) 4-CF3 C3H6 e-50 Ph 2- (OSO2CF3) 4-CF3 C3H6 e-51 Ph 2-Ph 4-CF3 C3H6 e-52 Ph 2- (pyridin-3-yl) 4-CF3 C3H6 e-53 Ph 2- (Y ⁿ Pr) 4-CF3 C3H6 e-54 Ph 2- (CH2CH = CH2) 4-CF3 C3H6 e-55 Ph 2- (O ⁿ Pr) 4-Cl C3H6 e-56 Ph 2- (OCH ₂ ⁱ Pr) 4-Cl CH2OCH2 e-57 Ph 2- ⁿ Bu 4-CF3 C3H6 e-58 Ph 2-'Pen 4-CF3 C3H6 e-59 Ph 2- (CBCHCECH) 4-CF3 C3H6 e-60 Ph 2- (CH = N-OH) 4-CF3 C3H6 e-61 Ph 2- (CH = N-OCH ₃ ) 4-CF3 C3H6 e-62 Ph 2- (OCH2CH (OCH3) 2) 4-CF3 C3H6 e-63 Ph 2- (OCH2CH2SO2CH) 4-CF3 C3H6 e-64 Ph 2- (OCH2Ph) 4-CF3 C3H6 e-65 Ph 2- (OCH ₂ - (pyridin-3-yl)) 4-CF3 C3H6 e-66 Ph 2- (OCH ₂ - [tetrahydrofuran-2-yl]) 4-CF3 C3H6 it's 67 Ph 2- (SCH2CH = CH2) 4-CF3 C3H6 e-68 Ph 2- (SCHCECH) 4-CF3 C3H6 e-69 Ph 2- (SO2CH3) 4-CF3 C3H6 e-70 Ph 2- (SO2CH2CH = CH2) 4-CF3 C3H6
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TABLE 7 (Continued) e-71 Ph 2- (OPh) 4-CF3 C3H6 e-72 Ph 2- (O- (pyridin-3-yl)) 4-CF3 C3H6 e-73 Ph 2-NH ₂ 4-CF3 C3H6 e-74 Ph 2- (N (CH ₃ ) ⁱ Pr) 4-CF3 C3H6
Table 45
TABLE 7 (Continued) At the. Cy ¹ (R ¹⁰ ) m (R ¹¹ ) n THE e-75 Ph 2- (NHCH ₂ CH = CH ₂ ) 4-CF3 C3H6 e-76 Ph 2- (NHCH ₂ CECH) 4-CF3 C3H6 e-77 Ph 2- (NHAc) 4-CF3 C3H6 e-78 Ph 2- (NHSO ₂ CH ₃ ) 4-CF3 C3H6 e-79 Ph 2- (NHSO ₂ Ph) 4-CF3 C3H6 e-80 Ph 2- (CONH2) 4-CF3 C3H6 e-81 Ph 2- (O-N = C (CH) 2) 4-CF3 C3H6 e-82 Ph 2- (SPh) 4-CF3 C3H6 e-83 Ph 2- (S- (pyridin-3-yl)) 4-CF3 C3H6 e-84 Ph 2- (CSPr) 4-CF3 C3H6 e-85 Ph 2- (CO (S ⁱ Pr)) 4-CF3 C3H6 e-86 Ph 2- (CS (O ⁱ Pr)) 4-CF3 C3H6 e-87 Ph 2- (CS2Pr) 4-CF3 C3H6 e-88 Ph 2- (Si (CH3) 3) 4-CF3 C3H6 e-89 Ph 2-NO ₂ 4-CF3 C3H6 e-90 Ph 2- (OCH2CO2CH3) 4-CF3 C3H6 e-91 Ph 2- (OCH2CH2) -3 4-CF3 C3H6 e-92 Ph 2- (OCH2CH2O) -3 4-CF3 C3H6 e-93 Ph 2- (OCH2O) -3 4-CF3 C3H6 e-94 Ph 2- (CH2OCH2CF3) 4-CF3 C3H6 e-95 Ph 2- (CH2OCH2CN) 4-CF3 C3H6
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TABLE 7 (Continued) At the. Cy ¹ (R ¹ °) m (R) n THE e-96 Ph 2- (CH ₂ OCH ₂ OCH ₃ ) 4-CF ₃ C ₃ Hg e-97 Ph 2- (CH ₂ OCH ₂ O ^c Pen) 4-CF ₃ C ₃ Hg e-98 Ph 2- (CH ₂ OCH ₂ Ac) 4-CF ₃ C ₃ H _S e-99 Ph 2- (CH ₂ OCH ₂ CH (OCH ₃ ) ₂ ) 4-CF ₃ C ₃ H _S e-100 Ph 2- (CH ₂ OCH ₂ SO ₂ CH ₃ ) 4-CF ₃ C ₃ H _S e-101 Ph 2- (CH ₂ OCH ₂ Ph) 4-CF ₃ C ₃ H _S
[Table 46]
TABLE 7 (Continued) At the. Cy ¹ (R ¹ °) m (R) n THE e-102 Ph 2- (CH ₂ OCH ₂ - (pyridin-3-yl)) 4-CF ₃ C ₃ H _S e-103 Ph 2- (CH ₂ OCH ₂ - [tetrahydrofuran-2-yl]) 4-CF ₃ C ₃ H _S e-104 Ph 3- (OCH ₂ 'Pr) 4-CF ₃ C ₃ H _S e-105 Ph 3- (OCH ₂ ^c Pr) 4-CF ₃ C ₃ H _S e-106 Ph 3- (CH ₂ OCH (OCH ₃ ) CH ₃ ) 4-CF ₃ C ₃ H _S e-107 Ph 3- (CO ₂ 'Pr) 4-CF ₃ C ₃ H _S e-108 Ph 3- (O ⁿ Pr) 4-CF ₃ C ₃ H _S e-109 Ph 2- (OCH ₂ 'Pr) 4-CN C ₃ H _S e-110 Ph 2- (OCH ₂ ^c Pr) 4-CN C ₃ H _S e-111 Ph 2- (CH ₂ OCH (OCH ₃ ) CH ₃ ) 4-CN C ₃ H _S e-112 Ph 2- (CO ₂ 'Pr) 4-CN C ₃ H _S e-113 Ph 2- (O ⁿ Pr) 4-CN C ₃ H _S
Chemical formula 41
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At the. ; r’V y _r , THE f-5 2-ÍOCH ₂ Pr) 4-CF ₃ c ₃ h _{ f-6 2-; OCH / Pr) 4-CF ₃ CsHe f-7 2-; ch ₂ och: ochj) ch ₃ ) 4-CF ₃ CsHe f-8 2-ÍCO ₂ Pr) 4-CF ₃ c _{£ 3} f-9 2-ÍOCH ₂ Pr) 4-CF ₃ ch ₂ och ₂ f-10 2-ÍOCH / PU 4-CF3 ch ₂ och ₂ f-11 2-; ch ₂ och; ocHj) ch ₃ ) 4-CF ₃ ch ₂ och ₂ f-12 2-ÍCO ₂ Pr) 4-CF ₃ ch ₂ och ₂
[Table 48]
TABLE 8 (continued) At the. (R ^{, 0} ) m (R ¹¹ ) n THE f-13 2- (0Et) 4-CF ₃ c ₃ h _s f-14 2-OH 4-CF ₃ c ₃ h _s f-15 2- (O ⁿ Bu) 4-CF ₃ c ₃ h _s f-16 2 - ([1,3] dioxolan-2-yl) 4-CF ₃ c ₃ h _s f-17 2- (CH ₂ OPr) 4-CF ₃ c ₃ h _s f-18 2- (CH ₂ OCH ₃ ) 4-CF ₃ c ₃ h _s f-19 2- (CH ₂ OEt) 4-CF ₃ c ₃ h _s f-20 2- (NHCH ₂ Pr) 4-CF ₃ c ₃ h _s f-21 2- (0Pr) 4-CF ₃ c ₃ h _s f-22 2- (O ^s Bu) 4-CF ₃ c ₃ h _s f-23 2- (OCO ₂ Pr) 4-CF ₃ c ₃ h _s f-24 2- (OCH ₂ CF ₃ ) 4-CF ₃ c ₃ h _s f-25 2- (OCH ₂ CH = CH ₂ ) 4-CF ₃ c ₃ h _s f-26 2- (OCH ₂ CH = C (CH ₃ ) ₂ ) 4-CF ₃ c ₃ h _s
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TABLE 8 (continued) f-27 2- (OCH ₂ ^t Bu) 4-CF3 C3H6 f-28 2- (OCH2CH = CCl2) 4-CF3 C3H6 f-29 2- (OCH ₂ CECH) 4-CF3 C3H6 f-30 2- (OCH2C (CHa) = CH2) 4-CF3 C3H6 f-31 2- (OCH ₂ ^s Bu) 4-CF3 C3H6 f-32 2- (OCH ₂ CN) 4-CF3 C3H6 f-33 2- (OCH (CHa) OCHa) 4-CF3 C3H6 f-34 2- (CO2Et) 4-CF3 C3H6 f-35 2- (OAc) 4-CF3 C3H6 f-36 2- (OCH ₂ [2,2-Cl ₂ -3-Ph- ^c Pr]) 4-CF3 C3H6 f-37 2- (OCH ₂ Ac) 4-CF3 C3H6 f-38 2- (OCH ₂ CH (OH) CH ₂ ) 4-CF3 C3H6 [Table 4 Í9]
TABLE 8 (continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE f-39 2- (OCH ₂ CH (OCH3) CH3) 4-CF3 C3H6 f-40 2- (The ^c Pen) 4-CF3 C3H6 f-41 2- (OCONH Pr) 4-CF3 C3H6 f-42 2- (OSO ₂ CF3) 4-CF3 C3H6 f-43 2-Ph 4-CF3 C3H6 f-44 2- (pyridin-3-yl) 4-CF3 C3H6 f-45 2- (Y ⁿ Pr) 4-CF3 C3H6 f-46 2- (CH ₂ CH = CH ₂ ) 4-CF3 C3H6 f-47 2- (O ⁿ Pr) 4-Cl C3H6 f-48 2- (OCH ₂ Pr) 4-Cl CH ₂ OCH ₂
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TABLE 8 (continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE f-49 2- ⁿ Bu 4-CF3 C3H6 f-50 2-Pen 4-CF3 C3H6 f-51 2- (CH ₂ CH ₂ CECH) 4-CF3 C3H6 f-52 2- (CH = N-OH) 4-CF3 C3H6 f-53 2- (CH = N-OCH ₃ ) 4-CF3 C3H6 f-54 2- (OCH ₂ CH (OCH3) ₂ ) 4-CF3 C3H6 f-55 2- (OCH ₂ CH ₂ SO ₂ CH) 4-CF3 C3H6 f-56 2- (OCH ₂ Ph) 4-CF3 C3H6 f-57 2- (OCH ₂ - (pyridin-3-yl)) 4-CF3 C3H6 f-58 2- (OCH ₂ - [tetrahydrofuran-2-yl]) 4-CF3 C3H6 f-59 2- (SCH ₂ CH = CH ₂ ) 4-CF3 C3H6 f-60 2- (SCH ₂ CECH) 4-CF3 C3H6 f-61 2- (SO ₂ CH3) 4-CF3 C3H6 f-62 2- (SO ₂ CH ₂ CH = CH ₂ ) 4-CF3 C3H6 f-63 2- (OPh) 4-CF3 C3H6
[Table 50]
TABLE 8 (continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE f-64 2- (O- (pyridin-3-yl)) 4-CF3 C3H6 f-65 2-NH ₂ 4-CF3 C3H6 f-66 2- (N (CH ₃ ) Pr) 4-CF3 C3H6 f-67 2- (NHCH ₂ CH = CH ₂ ) 4-CF3 C3H6 f-68 2- (NHCH ₂ CECH) 4-CF3 C3H6 f-69 2- (NHAc) 4-CF3 C3H6
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TABLE 8 (continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE f-70 2- (NHSO ₂ CH ₃ ) 4-CF3 C3H6 f-71 2- (NHSO ₂ Ph) 4-CF3 C3H6 f-72 2- (CONH ₂ ) 4-CF3 C3H6 f-73 2- (O-N = C (CH) 2) 4-CF3 C3H6 f-74 2- (SPh) 4-CF3 C3H6 f-75 2- (S- (pyridin-3-yl)) 4-CF3 C3H6 f-76 2- (CSPr) 4-CF3 C3H6 f-77 2- (CO (SPr)) 4-CF3 C3H6 f-78 2- (CS (OPr)) 4-CF3 C3H6 f-79 2- (CS2 ⁱ Pr) 4-CF3 C3H6 f-80 2- (Si (CH3) 3) 4-CF3 C3H6 f-81 2-NO ₂ 4-CF3 C3H6 f-82 2- (OCH ₂ CO ₂ CH3) 4-CF3 C3H6 f-83 2- (OCH ₂ CH ₂ ) -3 4-CF3 C3H6 f-84 2- (OCH ₂ CH ₂ O) -3 4-CF3 C3H6 f-85 2- (OCH ₂ O) -3 4-CF3 C3H6 f-86 2- (CH ₂ OCH ₂ CF3) 4-CF3 C3H6 f-87 2- (CH ₂ OCH ₂ CN) 4-CF3 C3H6 f-88 2- (CH ₂ OCH ₂ OCH) 4-CF3 C3H6 f-89 2- (CH ₂ OCH ₂ O ^C Pen) 4-CF3 C3H6
[Table 51]
TABLE 8 (Continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE f-90 2- (CH ₂ OCH ₂ Ac) 4-CF3 C3H6
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TABLE 8 (Continued) At the. (R ¹⁰ ) m (R ¹¹ ) n THE f-91 2- (CH2OCH ₂ CH (OCH3) 2) 4-CF3 C3H6 f-92 2- (CH ₂ OCH ₂ SO ₂ CH3) 4-CF3 C3H6 f-93 2- (CH ₂ OCH ₂ Ph) 4-CF3 C3H6 f-94 2- (CH ₂ OCH ₂ - (pyridin-3-yl)) 4-CF3 C3H6 f-95 2- (CH ₂ OCH ₂ - [tetrahydrofuran-2-yl]) 4-CF3 C3H6 f-96 3- (OCH ₂ ⁱ Pr) 4-CF3 C3H6 f-97 3- (OCH ₂ ^c Pr) 4-CF3 C3H6 f-98 3- (CH ₂ OCH (OCH3) CH3) 4-CF3 C3H6 f-99 3- (CO ₂ ⁱ Pr) 4-CF3 C3H6 f-100 3- (O ⁿ Pr) 4-CF3 C3H6 f-101 2- (OCH ₂ ⁱ Pr) 4-CN C3H6 f-102 2- (OCH ₂ ^c Pr) 4-CN C3H6 f-103 2- (CH ₂ OCH (OCH3) CH3) 4-CN C3H6 f-104 2- (CO ₂ ⁱ Pr) 4-CN C3H6 f-105 2- (O ⁿ Pr) 4-CN C3H6 [00276] The physical constants of some of the compounds in the TABE-
LAS 7 -8 are shown below.
[00277] Compound e-1: melting point [112 - 115 ° C] [00278] Compound e-2: melting point [118 - 123 ° C] [00279] Compound e-9: melting point [94 - 100 ° C] [00280] Compound e-11: melting point [105 - 110 ° C] [00281] Compound e-12: melting point [110 - 113 ° C] [00282] Compound e-13: ¹ H -RMN (CDCl ₃ , õppm, measuring temperature 20.2 ° C) 8.02 (s, 1H), 7.70 (d, 1H), 7.05 (d, 1 H), 5.70-5 , 66 (m,
1H), 3.96 (s, 3H), 3.52 (brs, 2H), 2.74-2.64 (m, 2H), 2.37-2.34 (m, 1H),
1.98-1.80 (m, 2H), 1.71-1.34 (m, 5H)
Petition 870170092471, of 11/29/2017, p. 131/143
129/134 [00283] Compound e-14: ¹ H-NMR (CDCl ₃ , δppm, measuring temperature 20.4 ° C) 7.34 (s, 1H), 7.23 (d, 1H), 6, 95 (d, 1H), 5.21 (s, 2H), 5.085.00 (m, 1H), 3.56-3.51 (brs, s, total 5H), 2.70-2.60 (m , 2H), 2.38-2.26 (m,
1H), 2.02-1.96 (m, 2H), 1.71-1.57 (m, 3H), 1.40-1.33 (m, 2H) [00284] Compound e-15: point melting point [104 - 107 ° C] [00285] Compound e-16: melting point [112 - 115 ° C] [00286] Compound e-17: ¹ H-NMR (CDCl ₃ , õppm, measurement temperature 21, 7 ° C) 7.17 (d, 1H), 7.07 (d, 1H), 5.01-4.97 (m, 1H), 4.35 (t, 2H), 3.47 (brs, 2H), 2.65-1.23 (m, 12H), 1.03 (t, 3H) [00287] Compound e-18: ¹ H-NMR (CDCl ₃ , δppm, measurement temperature 22.6 ° C ) 5.78 (s, 1H), 5.30-4.90 (m, 1H), 3.99 (t, 2H), 3.50 (brs, 2H), 2.66-2.29 (m , 3H), 1.96-1.15 (m, 11H), 0.95 (t, 3H) [00288] Some examples of preparation of the acaricide according to the present invention are shown below. However, additives and addition ratios are not limited to the preparation examples and can be modified over a wide range. In addition, the term "parts" used in the preparation examples indicates "parts by weight".
Preparation example 1 Humidifiable powder
Compound of the present invention 40 parts
Diatomaceous earth 53 parts
4 part fatty alcohol sulphate
Alkylnaphthalene sulphonate 3 parts [00289] The foregoing is mixed evenly and finely pulverized to obtain a humidifiable powder that includes 40% of the active ingredient.
Preparation example 2
Emulsion
Compound of the present invention 30 parts
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Xylene 33 pieces
Dimethylformamide 30 pieces
Polyoxyethylene alkylallyl ether 7 parts [00290] The above is mixed and dissolved to obtain an emulsion that includes 30% of the active ingredient.
[00291] The following test examples demonstrate that the cyclic amine compound or salt thereof according to the present invention is useful as an active ingredient in an acaricide.
Test Example 1: Efficacy Test Against Tetranychus urticae [00292] Seventeen adult female phosphorus-resistant mites of Tetranychus urticae were inoculated onto the first leaves of a bean plant in a No. 3 pot, 7 to 10 days after germination . Then, an emulsion was prepared having the formula indicated in Preparation Example 2 mentioned above. This emulsion was diluted with water to a compound concentration of 125 ppm, from which the diluted liquids were sprayed onto the bean plant. The bean plant was then placed in a room with controlled temperature at a temperature of 25 ° C and humidity of 65%. Mortality rates of the adult insect were investigated 3 days after spraying. The test was repeated twice.
[00293] The aforementioned test was carried out with emulsions containing the cyclic amine compounds of Compound No. H-1, H-2, H-5, H-29, H-41, H-42, H-43, H -51, H-52, H-54, H-55, H-56, H-57, H-58, H59, H-60, H-61, H-62, H-63, H-64, H -65, H-66, H-67, H-68, H-70, H-71, H-72, H-73, H-74, H-75, H-79, H-80, H-82 , H-83, H-84, H-85, H-86, H87, H-89, H-90, K-8, K-12, K-38, and K-39. As a result, insect mortality rates for all compounds in the case of dilution to a concentration of 125 ppm were 80% or more.
[00294] Additionally, the insect mortality rate for the
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Compound No. H-81, in the case of dilution to a concentration of 31 ppm, was also 80% or more.
Test Example 2: Efficacy Test against Panonychus citri [00295] Ten adult female mite-resistant Panonychus citri mites were inoculated onto a mandarin leaf placed in a Petri dish. Then, an emulsion was prepared having the formula indicated in Preparation Example 2 mentioned above. This emulsion was diluted with water to a compound concentration of 125 ppm, from which the diluted liquids were sprayed on the mandarin leaf with a rotary atomizer. The tangerine leaf was then placed in a room with controlled temperature at a temperature of 25 ° C and humidity of 65%. Mortality rates of the adult insect were investigated 3 days after spraying.
[00296] The aforementioned test was carried out with emulsions containing the cyclic amine compounds of Compound No. H-1, H-2, H-5, H-29, H-41, H-42, H-43, H -51, H-55, H-57, H-58, H-62, H-64, H-66, H69, H-72, H-73, H-74, H-75, H-81, H -82, H-83, H-84, H-85, H-87, H-89, H-90, K-8, K-12, K-38 and K-39. As a result, insect mortality rates for all compounds in the case of dilution to a concentration of 125 ppm were 80% or more.
[00297] Additionally, the insect mortality rate for Compound No. H-54, H-56, H-59, H-60, H-61, H-63, H-68, H-70, and H80 , in the case of dilution to a concentration of 31 ppm, was also 80% or more.
Test Example 3: Ovicidal Activity Test against Tetranychus urticae Eggs [00298] An adult female mite of Tetranychus urticae was inoculated onto a bean plant leaf placed on a
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Petri to allow the mite to lay eggs for 1 day. Then, an emulsion was prepared having the formula indicated in Preparation Example 2 mentioned above. This emulsion was diluted with water to a compound concentration of 125 ppm, after which the diluted liquid was sprayed onto the bean plant leaf with a rotary atomizer. The bean plant leaf was then placed in a room with controlled temperature at a temperature of 25 ° C and humidity of 65%. The egg mortality rate was calculated by investigating whether the eggs that were sprayed with the emulsion hatched or not.
[00299] The aforementioned test was performed with emulsions containing the cyclic amine compounds of Compound No. H-1, H-2, H-29, H-43, H-54, H-56 and H-73. As a result, egg mortality rates for all compounds in the case of dilution to a concentration of 125 ppm were 80% or more.
Test Example 4: Ovicidal Activity against Panonychus citri Eggs [00300] An adult female Panonychus citri mite was inoculated onto a mandarin leaf placed on a Petri dish to allow the mite to lay eggs for 1 day. Then, an emulsion was prepared having the formula indicated in Preparation Example 2 mentioned above. This emulsion was diluted with water to a compound concentration of 125 ppm, from which the diluted liquids were sprayed on the mandarin leaf with a rotary atomizer. The tangerine leaf was then placed in a room with controlled temperature at a temperature of 25 ° C and humidity of 65%. The egg mortality rate was calculated by investigating whether the eggs that were sprayed with the emulsion hatched or not. [00301] The aforementioned test was carried out with emulsions containing the cyclic amine compounds of Compound No. H-1, H-2, H-29,
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H-43, H-54, H-56 and H-73. As a result, egg mortality rates for all compounds in the case of dilution to a concentration of 125 ppm were 80% or more.
Test Example 5: Insecticidal Power Test against
Haemaphysalis longicornis [00302] A compound of the present invention was diluted with acetone to prepare a pharmaceutical solution that has a concentration of 400 ppm. 118 µl of the pharmaceutical solution was coated on the inside surface of a 20 ml glass bottle, followed by the volatilization of acetone to form a thin film of the compound of the present invention on the inside surface of the glass bottle. As the area of the glass vial was 47 cm ² , the amount of coating of the pharmaceutical solution per internal surface area was 1 pg / cm ² . Eight tick larvae Haemaphysalis longicornis were placed in the glass jar, followed by closing the glass jar and placing it in a temperature controlled room at 25 ° C. The insect mortality rate was calculated after 5 days. [00303] Insect mortality rate (%) = (number of dead ticks / number of released ticks) x 100 [00304] As a result, among the test compounds, the following compounds demonstrated an insect mortality rate of 80% or more:
[00305] Compound No .: H-5, H29, H-43, H-55, H-63, H-73, H-83, H90, J-42, K-38, K-39.
Test Example 6: Insecticidal Potency Test against Cat Fleas [00306] A compound of the present invention was diluted with acetone to prepare a solution of compound having a concentration of 400 ppm. 118 pL of the compound solution was coated on the inner surface of a 20 mL glass vial, followed by
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134/134 volatilization of acetone to form a thin film of the compound of the present invention on the inner surface of the glass bottle. As the area of the glass bottle was 47 cm ² , the amount of coating of the compound solution per internal surface area was 1 pg / cm ² . Eight cat flea larvae were placed in the glass jar, followed by closing the glass jar and placing it in a temperature controlled room at 25 ° C. The insect mortality rate was calculated after 1 day.
Insect mortality rate (%) = (number of dead ticks / number of released ticks) x 100 [00307] As a result, among the test compounds, the following compounds demonstrated an insect mortality rate of 80% or more:
Compound No .: H-73, K-38, K-39.
[00308] In view of the foregoing results, it is apparent that the cyclic amine compound or salt thereof according to the invention has a higher insecticidal potency against mites.
INDUSTRIAL APPLICABILITY [00309] The cyclic amine compound or salt thereof according to the invention makes it possible to effectively prevent acaricides that are harmful to agricultural crops or harmful in terms of hygiene.
[00310] The hydroxylamine compound or salt thereof according to the present invention makes it possible to easily synthesize the cyclic amine compound or salt thereof according to the invention. Therefore, the present invention is industrially useful.
Petition 870170092471, of 11/29/2017, p. 137/143
1/2

权利要求:
Claims (4)
[1]
1. A cyclic amine compound characterized by the fact that it is represented by formula (I) or a salt thereof:
R '
R in formula (I),
Cy ¹ represents a phenyl group;
Cy ² represents a pyridin-2-yl group;
R ^1b , R ^2b , R ^3a , R ^3b , R ^4a , R ^4b and R ^5a independently represent a hydrogen atom;
R ^1a and R ^2a bond to form a C3-6 alkylene group;
R ¹⁰ represents a C1-6 alkoxy group;
R ¹¹ represents a C1-6 haloalkyl group;
R ²⁰ represents a C1-6 haloalkyl group; m represents 1;
n represents 1;
p represents 1;
r represents 0;
Y represents an oxygen atom.
[2]
2. Compound of cyclic amine or salt thereof, according to claim 1, characterized by the fact that in formula (I),
R ^1a and R ^2a bond to form a propylene group;
R ¹⁰ represents an n-propoxy group;
R ¹¹ represents a trifluoromethyl group;
R ²⁰ represents a trifluoromethyl group.
[3]
3. Pest control agent characterized by the fact that it comprises at least one cyclic amine compound or a salt
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2/2 of that as defined in claim 1 or 2, as an active ingredient.
[4]
4. Acaricide characterized by the fact that it comprises at least one cyclic amine compound or a salt thereof as defined in claim 1 or 2, as an active ingredient.
Petition 870170092471, of 11/29/2017, p. 139/143

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引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

---

US2970144A|1957-12-11|1961-01-31|Smith Kline French Lab|Esters of 9-alkyl-3-oxa and 3-thia-9-azabicyclo [3. 3. 1]-nonan-7-ol|

---

DE3670085D1|1985-04-29|1990-05-10|Ciba Geigy Ag|2- DIBENZODIOXAPHOSPHEPINE AND DIBENZODIOXAPHOSPHOCINE.|

---

US4808645A|1985-04-29|1989-02-28|Ciba-Geigy Corporation|6-dibenzodioxaphosphepin and dioxaphosphocin process stabilizers|

---

US5145893A|1989-03-21|1992-09-08|Ciba-Geigy Corporation|Non-migrating 1-hydrocarbyloxy hindered amine derivatives as polymer stabilizers|

---

PT97637B|1990-05-11|1998-08-31|Sankyo Co|PROCESS FOR THE PREPARATION OF PIPERIDYLOXY AND QUINUCLIDYNYLOXY-ISOXAZOLIC DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM|

---

KR100193146B1|1990-07-20|1999-06-15|월터 클리웨인, 한스-피터 위트린|Stabilized Monomer Composition|

---

US5187166A|1990-07-31|1993-02-16|Nisshin Flour Milling Co., Ltd.|Azabicyclo derivatives and their use as antiemetics|

---

US5216156A|1992-05-05|1993-06-01|Ciba-Geigy Corporation|Non-migrating 1-hydrocarbyloxy-2,2,6,6-tetramethylpiperidine 1,3,5-triazine derivatives|

---

IL109104A|1993-03-26|1998-08-16|Shell Int Research|2,6-substituted pyridine derivatives their preparation and herbicidal compositions containing them|

---

JP3829879B2|1994-05-18|2006-10-04|大正製薬株式会社|Quinoline carboxylic acid derivatives|

---

WO2000071536A1|1999-05-20|2000-11-30|E.I. Du Pont De Nemours And Company|Heteroaryloxypyrimidine insecticides and acaricides|

---

EP1420644B1|2001-08-23|2006-05-31|Bayer CropScience S.A.|Substituted propargylamines|

---

JP4409944B2|2001-09-28|2010-02-03|クミアイ化学工業株式会社|Difluoroalkene derivative, pest control agent containing the same, and production intermediate thereof|

---

AU2005228289B2|2004-03-31|2008-01-10|Nippon Soda Co., Ltd.|Cyclic amine compound and pest control agent|

---

JP2009504773A|2005-08-19|2009-02-05|エランファーマシューティカルズ，インコーポレイテッド|Bridged N-bicyclic sulfonamide inhibitors of gamma secretase|

---

TW200745101A|2005-09-30|2007-12-16|Organon Nv|9-Azabicyclo[3.3.1]nonane derivatives|

---

SI1947098T1|2005-10-06|2012-02-29|Nippon Soda Co|Cyclic amine compounds and pest control agent|

---

UA86328C2|2005-10-06|2009-04-10|Ниппон Сода Ко., Лтд.|Bridged cyclic amine compound and pest control agent|

---

BRPI0716240B8|2006-09-01|2019-09-17|Oat Agrio Co Ltd|n-pyridylpiperidine compound, method for its production, and pest control agent|

---

US20080200405A1|2007-02-16|2008-08-21|Ghanshyam Patil|Drug Resistance Reversal In Neoplastic Disease|

---

CN103497148B|2007-02-22|2016-06-01|科尔比制药公司|Hydroxylamine compound and usage thereof|

---

WO2008126795A1|2007-04-06|2008-10-23|Nippon Soda Co., Ltd.|Pest control agent composition and method of pest control|

---

EP2195315B1|2007-08-15|2017-01-18|Merck Sharp & Dohme Corp.|Substituted bicyclic piperidinyl-and piperazinyl- sulfonamides useful to inhibit 11 -hydroxysteroid dehydrogenase type-1|

---

JP5258771B2|2007-08-30|2013-08-07|日本曹達株式会社|Method for producing cis-3-substituted-3-azabicyclo [3.2.1] octane-8-ol derivative|

---

MX2010004450A|2007-10-22|2010-05-05|Schering Corp|Bicyclic heterocycle derivatives and methods of use thereof.|

---

WO2009080554A1|2007-12-21|2009-07-02|Basf Se|Flame retardant compositions comprising sterically hindered amines|

---

JP5188316B2|2008-08-06|2013-04-24|株式会社Ｉｈｉ|Mobile robot and traveling speed control method of mobile robot|

---

JP5299759B2|2008-11-11|2013-09-25|株式会社リコー|Image forming apparatus|

---

JP5235742B2|2009-03-24|2013-07-10|能美防災株式会社|Alarm|

---

TWI471095B|2009-12-21|2015-02-01|Nippon Soda Co|Cyclic amine compounds and acaricides|JP5767099B2|2011-06-16|2015-08-19|日本曹達株式会社|Cyclic amine compounds and pest control agents|

---

JP2013170128A|2012-02-17|2013-09-02|Nippon Soda Co Ltd|N-oxyl cyclic amine compound|

---

JP2013241352A|2012-05-18|2013-12-05|Nippon Soda Co Ltd|Pest controlling agent composition and pest controlling method|

---

PE20171735A1|2015-02-17|2017-12-04|Nippon Soda Co|AGROCHEMICAL COMPOSITION|

---

WO2017018409A1|2015-07-28|2017-02-02|日本曹達株式会社|Pyridine-2-yl-pyridinium compound and method of using same|

---

EP3381903B1|2015-11-25|2020-12-30|UBE Industries, Ltd.|Pentafluorosulfanylpyridine|

---

JP2019131469A|2016-05-11|2019-08-08|日本曹達株式会社|Pest control method, and agent composition for pest control and pest control agent set|

---

BR112018076951A2|2016-07-12|2019-04-02|Basf Agrochemical Products B.V.|pesticide mixtures, methods for insect control, plant protection and protection of plant propagating material, seed and pesticide composition|

---

BR112019009529A2|2016-11-11|2019-07-30|Bayer Animal Health Gmbh|new quinoline derivatives|

---

CN110382493A|2016-12-16|2019-10-25|拜耳农作物科学股份公司|Thiadiazoles derivative as pesticide|

---

CN110461854A|2017-03-31|2019-11-15|巴斯夫欧洲公司|The method for preparing chirality 2,3- thiazoline simultaneously [3,2-A] pyrimidine -4- compound|

---

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---

TW201841904A|2017-04-27|2018-12-01|德商拜耳廠股份有限公司|Heteroarylphenylaminoquinolines and analogues|

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EP3619197A1|2017-05-03|2020-03-11|Bayer Aktiengesellschaft|Trisubstitutedsilylmethylphenoxyquinolines and analogues|

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EP3618632A1|2017-05-03|2020-03-11|Bayer Aktiengesellschaft|Trisubstitutedsilylheteroaryloxyquinolines and analogues|

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WO2018202715A1|2017-05-03|2018-11-08|Bayer Aktiengesellschaft|Trisubstitutedsilylbenzylbenzimidazoles and analogues|

---

PE20200608A1|2017-06-30|2020-03-10|Bayer Animal Health Gmbh|NEW DERIVATIVES OF AZAQUINOLINE|

---

EP3284739A1|2017-07-19|2018-02-21|Bayer CropScience Aktiengesellschaft|Substitutedaryl compounds as pesticides|

---

AU2018311019A1|2017-08-04|2020-01-30|Bayer Animal Health Gmbh|Quinoline derivatives for treating infections with helminths|

---

EP3668312A1|2017-08-17|2020-06-24|Bayer CropScience LP|Liquid fertilizer-dispersible compositions and methods thereof|

---

CN111108106A|2017-08-22|2020-05-05|拜耳公司|Heterocyclic derivatives as pest control agents|

---

WO2019042932A1|2017-08-31|2019-03-07|Basf Se|Method of controlling rice pests in rice|

---

EP3453706A1|2017-09-08|2019-03-13|Basf Se|Pesticidal imidazole compounds|

---

AU2018344370A1|2017-10-04|2020-04-23|Bayer Aktiengesellschaft|Derivatives of heterocyclic compounds as pest control agents|

---

CN111201227A|2017-10-13|2020-05-26|巴斯夫欧洲公司|Imidazolidine pyrimidinium compounds for combating animal pests|

---

ES2894107T3|2017-10-18|2022-02-11|Bayer Ag|Combinations of active compounds with insecticidal/acaricidal properties|

---

JP2020537638A|2017-10-18|2020-12-24|バイエル・アクチエンゲゼルシヤフト|Combination of active compounds with insecticidal / acaricidal properties|

---

EP3473100A1|2017-10-18|2019-04-24|Bayer Aktiengesellschaft|Active compound combinations having insecticidal/acaricidal properties|

---

US20200236938A1|2017-10-18|2020-07-30|Bayer Aktiengesellschaft|Active compound combinations having insecticidal/acaricidal properties|

---

US11191271B2|2017-10-18|2021-12-07|Bayer Aktiengesellschaft|Active compound combinations having insecticidal/acaricidal properties|

---

TW201930279A|2017-10-18|2019-08-01|德商拜耳廠股份有限公司|Active compound combinations having insecticidal/acaricidal properties|

---

BR112020005191A2|2017-10-30|2020-09-15|Nippon Soda Co., Ltd.|composition of agrochemical emulsifiable concentrate|

---

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---

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---

WO2019121143A1|2017-12-20|2019-06-27|Basf Se|Substituted cyclopropyl derivatives|

---

TW201927768A|2017-12-21|2019-07-16|德商拜耳廠股份有限公司|Trisubstitutedsilylmethylheteroaryloxyquinolines and analogues|

---

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---

WO2019137995A1|2018-01-11|2019-07-18|Basf Se|Novel pyridazine compounds for controlling invertebrate pests|

---

BR112020016234A2|2018-02-12|2020-12-15|Bayer Aktiengesellschaft|FUNGICIDED OXADIAZOLS|

---

WO2019162228A1|2018-02-21|2019-08-29|Bayer Aktiengesellschaft|1-but-3-en derivatives and their use as fungicides|

---

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---

WO2019166558A1|2018-02-28|2019-09-06|Basf Se|Use of pyrazole propargyl ethers as nitrification inhibitors|

---

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---

WO2019166560A1|2018-02-28|2019-09-06|Basf Se|Use of n-functionalized alkoxy pyrazole compounds as nitrification inhibitors|

---

CN111836815A|2018-03-12|2020-10-27|拜耳公司|Fused bicyclic heterocyclic derivatives as pest control agents|

---

JPWO2019176676A1|2018-03-13|2021-02-25|日本曹達株式会社|Pest control method and pest control agent composition|

---

WO2019175713A1|2018-03-14|2019-09-19|Basf Corporation|New catechol molecules and their use as inhibitors to p450 related metabolic pathways|

---

WO2019175712A1|2018-03-14|2019-09-19|Basf Corporation|New uses for catechol molecules as inhibitors to glutathione s-transferase metabolic pathways|

---

CA3096497A1|2018-04-10|2019-10-17|Bayer Aktiengesellschaft|Oxadiazoline derivatives|

---

WO2019197615A1|2018-04-13|2019-10-17|Bayer Aktiengesellschaft|Active ingredient combinations with fungicides, insecticides and acaricidal properties|

---

CN111970929A|2018-04-13|2020-11-20|拜耳公司|Active ingredient combinations having insecticidal, nematicidal and acaricidal properties|

---

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---

WO2019201921A1|2018-04-20|2019-10-24|Bayer Aktiengesellschaft|Heterocyclene derivatives as pest control agents|

---

SG11202009464PA|2018-04-20|2020-10-29|Bayer Ag|Heteroaryl-triazole and heteroaryl-tetrazole compounds as pesticides|

---

US20210139468A1|2018-05-09|2021-05-13|Bayer Animal Health Gmbh|New quinoline derivatives|

---

WO2019219529A1|2018-05-15|2019-11-21|Basf Se|Mixtures comprising benzpyrimoxan and oxazosulfyl and uses and methods of applying them|

---

WO2019224092A1|2018-05-22|2019-11-28|Basf Se|Pesticidally active c15-derivatives of ginkgolides|

---

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---

CN112512315A|2018-06-25|2021-03-16|拜耳作物科学有限合伙公司|Seed treatment method|

---

WO2020002472A1|2018-06-28|2020-01-02|Basf Se|Use of alkynylthiophenes as nitrification inhibitors|

---

TW202035386A|2018-07-05|2020-10-01|德商拜耳廠股份有限公司|Substituted thiophenecarboxamides and analogues|

---

CN112424147A|2018-07-23|2021-02-26|巴斯夫欧洲公司|Use of substituted thiazolidine compounds as nitrification inhibitors|

---

EP3826983A1|2018-07-23|2021-06-02|Basf Se|Use of substituted 2-thiazolines as nitrification inhibitors|

---

WO2020020813A1|2018-07-25|2020-01-30|Bayer Aktiengesellschaft|Fungicidal active compound combinations|

---

WO2020020816A1|2018-07-26|2020-01-30|Bayer Aktiengesellschaft|Novel triazole derivatives|

---

EP3613736A1|2018-08-22|2020-02-26|Basf Se|Substituted glutarimide derivatives|

---

EP3849975A1|2018-09-13|2021-07-21|Bayer Aktiengesellschaft|Heterocyclene derivatives as pest control agents|

---

EP3852532A1|2018-09-17|2021-07-28|Bayer Aktiengesellschaft|Use of the fungicide isoflucypram for controlling claviceps purpurea and reducing sclerotia in cereals|

---

AU2019348280A1|2018-09-28|2021-04-22|Basf Se|Method of controlling pests by seed treatment application of a mesoionic compound or mixture thereof|

---

EP3628157A1|2018-09-28|2020-04-01|Basf Se|Method of controlling insecticide resistant insects and virus transmission to plants|

---

EP3628158A1|2018-09-28|2020-04-01|Basf Se|Pesticidal mixture comprising a mesoionic compound and a biopesticide|

---

EP3628156A1|2018-09-28|2020-04-01|Basf Se|Method for controlling pests of sugarcane, citrus, rapeseed, and potato plants|

---

WO2020070050A1|2018-10-01|2020-04-09|Bayer Aktiengesellschaft|Fungicidal 5-substituted imidazol-1-yl carbinol derivatives|

---

CA3116626A1|2018-10-18|2020-04-23|Bayer Aktiengesellschaft|Heteroarylaminoquinolines and analogues|

---

CA3116629A1|2018-10-18|2020-04-23|Bayer Aktiengesellschaft|Pyridylphenylaminoquinolines and analogues|

---

TW202028193A|2018-10-20|2020-08-01|德商拜耳廠股份有限公司|Oxetanylphenoxyquinolines and analogues|

---

EP3643711A1|2018-10-24|2020-04-29|Bayer Animal Health GmbH|New anthelmintic compounds|

---

EP3643705A1|2018-10-24|2020-04-29|Basf Se|Pesticidal compounds|

---

CN109964940A|2018-11-14|2019-07-05|东莞东阳光科研发有限公司|A kind of application of miticide composition and its preparation, miticide composition and preparation|

---

AR117169A1|2018-11-28|2021-07-14|Bayer Ag| PYRIDAZINE AMIDES AS FUNGICIDE COMPOUNDS|

---

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---

WO2020126980A1|2018-12-18|2020-06-25|Bayer Aktiengesellschaft|Active compound combinations having insecticidal/acaricidal properties|

---

WO2020127780A1|2018-12-20|2020-06-25|Bayer Aktiengesellschaft|Heterocyclyl pyridazine as fungicidal compounds|

---

UY38525A|2018-12-21|2020-07-31|Bayer Ag|1,3,4-OXADIAZOLES AND DERIVATIVES THEREOF AS NEW FUNGICIDE AGENTS|

---

EP3669652A1|2018-12-21|2020-06-24|Bayer AG|Active compound combination|

---

EP3679793A1|2019-01-08|2020-07-15|Bayer AG|Active compound combinations|

---

EP3679791A1|2019-01-08|2020-07-15|Bayer AG|Active compound combinations|

---

EP3679792A1|2019-01-08|2020-07-15|Bayer AG|Active compound combinations|

---

EP3679789A1|2019-01-08|2020-07-15|Bayer AG|Active compound combinations|

---

EP3679790A1|2019-01-08|2020-07-15|Bayer AG|Active compound combinations|

---

EP3696177A1|2019-02-12|2020-08-19|Basf Se|Heterocyclic compounds for the control of invertebrate pests|

---

WO2020178067A1|2019-03-01|2020-09-10|Bayer Aktiengesellschaft|Active compound combinations having insecticidal/acaricidal properties|

---

WO2020178307A1|2019-03-05|2020-09-10|Bayer Aktiengesellschaft|Active compound combination|

---

WO2020182929A1|2019-03-13|2020-09-17|Bayer Aktiengesellschaft|Substituted ureas and derivatives as new antifungal agents|

---

WO2020187656A1|2019-03-15|2020-09-24|Bayer Aktiengesellschaft|Active compound combinations having insecticidal/acaricidal properties|

---

CN109964948A|2019-05-05|2019-07-05|湖南速博生物技术有限公司|A kind of Pesticidal combination|

---

WO2020231751A1|2019-05-10|2020-11-19|Bayer Cropscience Lp|Active compound combinations|

---

CN113923987A|2019-05-29|2022-01-11|巴斯夫欧洲公司|Mesoionic imidazolium compounds and derivatives for combating animal pests|

---

WO2020254492A1|2019-06-21|2020-12-24|Bayer Aktiengesellschaft|Hydroxyisoxazolines and derivatives thereof|

---

WO2020254493A1|2019-06-21|2020-12-24|Bayer Aktiengesellschaft|Thienylhydroxyisoxazolines and derivatives thereof|

---

WO2020254494A1|2019-06-21|2020-12-24|Bayer Aktiengesellschaft|Fungicidal oxadiazoles|

---

WO2020254490A1|2019-06-21|2020-12-24|Bayer Aktiengesellschaft|Phenoxyphenyl hydroxyisoxazolines and analogues as new antifungal agents|

---

WO2020254486A1|2019-06-21|2020-12-24|Bayer Aktiengesellschaft|Hydroxyisoxazolines and derivatives thereof|

---

WO2020254487A1|2019-06-21|2020-12-24|Bayer Aktiengesellschaft|Hydroxyisoxazolines and derivatives thereof|

---

WO2020254489A1|2019-06-21|2020-12-24|Bayer Aktiengesellschaft|Benzylphenyl hydroxyisoxazolines and analogues as new antifungal agents|

---

WO2020254488A1|2019-06-21|2020-12-24|Bayer Aktiengesellschaft|Hydroxyisoxazolines and use thereof as fungicides|

---

WO2021001331A1|2019-07-03|2021-01-07|Bayer Aktiengesellschaft|Substituted thiophene carboxamides and derivatives thereof as microbicides|

---

EP3766879A1|2019-07-19|2021-01-20|Basf Se|Pesticidal pyrazole derivatives|

---

EP3769623A1|2019-07-22|2021-01-27|Basf Se|Mesoionic imidazolium compounds and derivatives for combating animal pests|

---

TW202120490A|2019-07-30|2021-06-01|德商拜耳動物保健有限公司|New isoquinoline derivatives|

---

CN110547299A|2019-09-02|2019-12-10|陕西上格之路生物科学有限公司|Acanenapyr-containing acaricidal composition, preparation formulation and application|

---

CN110637824A|2019-10-09|2020-01-03|陕西上格之路生物科学有限公司|Acaricidal composition containing Acynonapyr, preparation formulation and application thereof|

---

WO2021123051A1|2019-12-20|2021-06-24|Bayer Aktiengesellschaft|Substituted thiophene carboxamides, thiophene carboxylic acids and derivatives thereof|

---

TW202135662A|2019-12-20|2021-10-01|德商拜耳廠股份有限公司|Thienyloxazolones and analogues|

---

CN112715565B|2020-01-11|2021-12-10|青岛海利尔生物科技有限公司|Acaricidal composition containing Acynonapyr|

---

EP3708565A1|2020-03-04|2020-09-16|Bayer AG|Pyrimidinyloxyphenylamidines and the use thereof as fungicides|

---

WO2021204930A1|2020-04-09|2021-10-14|Bayer Animal Health Gmbh|Substituted condensed azines as anthelmintic compounds|

---

WO2021209368A1|2020-04-16|2021-10-21|Bayer Aktiengesellschaft|Active compound combinations and fungicide compositions comprising those|

---

UY39169A|2020-04-16|2021-11-30|Bayer Ag|COMBINATIONS OF ACTIVE COMPOUNDS, FUNGICIDE COMPOSITIONS THAT COMPRISE THEM, USE OF THE SAME AND METHODS TO CONTROL MICROORGANISMS|

---

WO2021209365A1|2020-04-16|2021-10-21|Bayer Aktiengesellschaft|Active compound combinations and fungicide compositions comprising those|

---

WO2021209366A1|2020-04-16|2021-10-21|Bayer Aktiengesellschaft|Active compound combinations and fungicide compositions comprising those|

---

WO2021209364A1|2020-04-16|2021-10-21|Bayer Aktiengesellschaft|Active compound combinations and fungicide compositions comprising those|

---

WO2021209490A1|2020-04-16|2021-10-21|Bayer Aktiengesellschaft|Cyclaminephenylaminoquinolines as fungicides|

---

WO2021224220A1|2020-05-06|2021-11-11|Bayer Aktiengesellschaft|Pyridine amides as fungicidal compounds|

---

WO2021228734A1|2020-05-12|2021-11-18|Bayer Aktiengesellschaft|Triazine and pyrimidine amides as fungicidal compounds|

---

WO2021233861A1|2020-05-19|2021-11-25|Bayer Aktiengesellschaft|Azabicyclicamides as fungicidal compounds|

---

WO2021245087A1|2020-06-04|2021-12-09|Bayer Aktiengesellschaft|Heterocyclyl pyrimidines and triazines as novel fungicides|

---

WO2021249995A1|2020-06-10|2021-12-16|Bayer Aktiengesellschaft|Azabicyclyl-substituted heterocycles as fungicides|

---

WO2021255071A1|2020-06-18|2021-12-23|Bayer Aktiengesellschaft|3--5,6-dihydro-4h-1,2,4-oxadiazine derivatives as fungicides for crop protection|

---

WO2021255091A1|2020-06-19|2021-12-23|Bayer Aktiengesellschaft|1,3,4-oxadiazoles and their derivatives as fungicides|

---

WO2021255089A1|2020-06-19|2021-12-23|Bayer Aktiengesellschaft|1,3,4-oxadiazole pyrimidines and 1,3,4-oxadiazole pyridines as fungicides|

---

WO2021255169A1|2020-06-19|2021-12-23|Bayer Aktiengesellschaft|1,3,4-oxadiazole pyrimidines as fungicides|

---

WO2021255170A1|2020-06-19|2021-12-23|Bayer Aktiengesellschaft|1,3,4-oxadiazole pyrimidines as fungicides|

---

EP3915371A4|2020-11-04|2021-12-01|Bayer Ag|Active compound combinations and fungicide compositions comprising those|

---

EP3915971A4|2020-12-16|2021-12-01|Bayer Ag|Phenyl-sn-phenylamidines and the use thereof as fungicides|

法律状态:
2016-09-20| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|

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2017-09-05| B06A| Patent application procedure suspended [chapter 6.1 patent gazette]|

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2018-02-27| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|

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2018-03-27| B16A| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]|

优先权:

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申请号 | 申请日 | 专利标题

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JP2010-039839|2010-02-25|

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JP2010039839|2010-02-25|

---

JP2010-117392|2010-05-21|

---

JP2010117392|2010-05-21|

---

JP2010224844|2010-10-04|

---

JP2010-224844|2010-10-04|

---

PCT/JP2011/054173|WO2011105506A1|2010-02-25|2011-02-24|Cyclic amine compound and miticide|

---