前苏联专利SU1648250A3 Method for preparation of 6-(acylaminoaryl)-4,5-dihydro-3(2h)-pyridazino-derivatives or theirs pharm

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专利摘要:
The invention relates to heterocyclic compounds, in particular to the preparation of 6- (acylaminoaryl) -4,5-dihydro-3 (2H) -pyridazine derivatives or their pharmaceutically acceptable salts. The goal is to develop a method for obtaining these compounds. Prepared from the halo of the derivative of 6- (alkanoylaminoaryl) -4,5-dihydro-3 (2H) -pyridaine and imidazole or, if necessary, the corresponding compound, 9 tab.
公开号:SU1648250A3
申请号:SU843692325
申请日:1984-01-20
公开日:1991-05-07
发明作者:Андрей Росси Филипп；Тиес Марко；Франке Альбрехт；Кениг Хорст；Леманн Ханс-Дитер；Грис Йозеф；Фридрих Людвиг；Ленке Дитер
申请人:Басф Аг (Фирма)；
IPC主号:

专利说明:

The invention relates to the production of new 6- (acylaminoaryl) -4,5-dihydro-3 (2H) -pyridazine derivatives, which cushion inhibit platelet aggregation, antihypertensive, suppress the allotment of gastric juice or positive isotropic properties.
The purpose of the invention is to obtain new 6- (acylaminoaryl) -4,5-dihydro-3- (2H) - pyridazinones, which have valuable pharmacological properties with low toxicity.
An example. 5.8 g (20 mmol) of 6-Gp- (3-chloropropionylamino) phenyl-4,5-dihydro-3 (2H) -pyridazinone is stirred for 8 hours at 80 ° C with 3.5 g (25 mmol) of potassium carbonate and 2.17 g (25 mmol) of morpholine in 50 ml of dimethylformamide. After the addition of 500 g of ice (water), the crystallized ice is sucked off. ,
After recrystallization from dimethylformamide, the water is dried under high vacuum at 50 ° C and 5.4 g (82%) of 6- (p-3- (1-morpholino) -propionyl-aminophenyl) -4,5-dngydro-3 are obtained. (2H) -Zyrid pyridide in the form of colorless crystals. T 183-185 ev.
Analogously to Example 1, the compounds of Examples 2-102 are obtained (see Table 1). If the compounds are isolated as oils, they can be purified by extraction with methylene chloride and / or chromatography on a column using slice gel or alumina with mixtures of methylene chloride / methanol as g solvents.
Analogously to example 1 is obtained by conversion of 6-- (3-chloropropionyl-. Mino) -phenyl-4,5-dihydro-3 (2H) -pyriЈ
00
HS On

and
dazinona compounds of examples 103-105, are given in table.2.
Analogously to Example I, prepared from 6-fn- (3-chloropropionylamino) -phenyl-3 (2H) -pyridazinone and 6-Јn- (3-chloropropionylamino) -phenyl} -5-methyl 3 (2H) -pyridazinone or, respectively, (3-chloropropionylamino) -phenylT-b-methyl 3 (2H) -pyridazinone, the compounds of Examples 106-115 listed in Table 3.

Analogously to Example 1, it is prepared by reacting 6-Gp- (chloro- or bromoalkanoyl (amino) -phenshG-5-methyl-3 (2H) -pyridazinok with 4-phenylpiperidine or phenylpiperazine) of the compounds of Examples 116-126 listed in Table 4.
Example
g f
,, 127. 6- {p-z- (2-phenyl ethylamino) propionylamino | -phenyl (- 4, 5-dihydro-3 (2H) -pyridazinone.
11.18 g (40 mmol) of 6-Gp- (3-chloropropionylamino) -phenyl1-4,5-dihydro-3 (2H) -pyridazinone-B injected with 250 ml of ethanol. After adding dropwise, 26.5 g (220 mmol) of 2-phenylethylamine are boiled for 6 hours under reflux. The insoluble parts are filtered off and the mother liquor, after removal of the solvent, is crystallized by the addition of acetone. After double recrystallization from methanol, 5.3 g of 6-Gn-p- (2 phenyl ethylamino) propionylamino-phenyl | -4,5-dihydro-3 (2H) -pyridazinone-HC1 are obtained. T 2b9-270 ° C.
To convert to the free base, the resulting hydrochloride is dissolved in methanol and an equimolar amount of sodium methoxide is added. After removing the solvent and adding water, the substance is extracted with methylene chloride. After drying the methylene chloride phase over and removing the solvent, the substance is mixed and sucked off. 6- | p-13- (2-phenyl-ethylamino) propionylamine-phenyl | -4,5-dihydro-3- (2H) -pyridazinone is obtained. T
P
13 ° 132 ° C.
Pharmacological tests of the obtained compounds were carried out according to the following methods.
1, Inhibition of collagen-induced human platelet aggregation in vitro.
Platelet-rich plasma is obtained by centrifuging the coronary
g
five
0
5 Qg
0 5
0
five
citrated blood (300 g, 10 min at 4 ° C). Photometric measurement of platelet aggregation is carried out with the addition of MgClj (final concentration 10 mmol / l) and Stago type collagen (final concentration 0.02 mg / ml) in a Vorn MKZ aggregometer. A measure of aggregation is the maximum extinction change per second.
The aggregation inhibitory activity of the substances is checked after an incubation period of 10 minutes.
As an EC of 50%, the concentration causing 50% inhibition of aggregation, given in Table 5, is determined.
In experiment I, the tested substances showed the values given in table 6.
2. Lowering blood pressure effect on rat. Under general anesthesia.
To study the blood pressure lowering groups of 3-5 male rats of the strain Sprague-Dawley (240-280 g) under urethral anesthesia, the substance is administered intraperitoneally or intravenously (1.78 mg / kg intraperitoneally).
The blood pressure in the carotid artery is measured using a Statham probe. As the ED of 20%, the dose is determined, which reduces the average blood pressure in the carotid artery by 20%, given in Table 7.
In terms of their toxicity, Compounds 1 are or are less toxic than known compounds.
In run 2 (decrease in blood pressure), the values given in table 8 were determined.
3. Inhibition of gastric acid secretion.
Inhibition of acid secretion of gastric acid is expressed in increasing the pH value of the gastric mucosa. It was tested in groups of 4 female rats of the Sprageu-Dawley strain (160-180 g). Animals did not receive any feed within 48 hours (water if desired). They receive in advance (through the mouth) various doses of the tested substances. After 1 hour, animals are anesthetized with sodium hexaborbarbital (46.4 mg / kg i.v.). Then the pH electrode is inserted into the Foam electrode and from the p
The method of obtaining 6- (acnlamino, aryl) -A, 5-dihydro-3 (2H) -pyridazino derivatives of the general formula
RiRZ
fVRj-CONH
N-NH
de, the substituents of the phenylene residue are relative to each other in the position of meta or vapor {A and B are hydrogen or together form a bond; 5 RJ is hydrogen or C-C alkyl; Rg, is hydrogen or R j and R together represent an alkylene residue, with the proviso that A and B are hydrogen, 40 R3 is Cj-C alkylene with an unbranched, straight chain, unsubstituted or substituted by one to two C-Su-alkyls ; R, j.-a) imidazol-1 -yl or d5) a group of the general formula
/ N
(CH2) m
where the dotted line indicates an additional bond; R,
and mean hydrogen, alkyl residues, unsubstituted or R substitutions, are the same or different 6
m 0,1;
or R and Rg
together form an al, keene chain with, or c) a group of the general formula
25
R9-N-CH2-CH2-N- (CH2) PX
where is rft 9

hydrocarbon residue Cj-Cj or C (Ј, unsubstituted or substituted by phenyl, unsubstituted or substituted by a label-sigroup, hysteroaryl with 5-6 ring members, which may contain an oxygen atom;
p 2,3, or g) a group of the general formula
- N RIO R “,

where r
(about
and hydrogen atoms, hydrocarbon residues. , unsubstituted or substituted with one or two phenyls, or cycloalkyl groups Cj-Cjj, unsubstituted, scandinic or substituted with phenyl, or adamantyl residues, or benzo-condensed cycloalkyl1 groups Cy-C7t or d), a group of the formula
B5
(W2) 2
)
R13 ACH2-N,
de R and R, a hydrogen, halogen atoms, alkyl or alkoxy residues, or
a group of the general formula
R | VA
ЈЈ
RB
de G - oxygen or sulfur atom;
Rj4 and RJC H or C | -C ralkyl, provided that if R., R, A and B mean
ten
15
hydrogen atoms, then RJ does not mean methylene, unsubstituted or substituted by alkyl CJ-GJ-, and if R, A and B denote 20 hydrogen atoms, then Rf means a hydrogen atom or alkyl, RJ means methylene, unsubstituted
25
or substituted by alkyl, R does not mean a group of the formula according to claim 5, where Rj9 is hydrogen or Cd-Cc. al-kil,
or their pharmaceutically acceptable salts, characterized in that the compound of the general formula
Ri R2
-M-ifi
five
0
Nn n
2 and R3 have
five
X-R3-CONH
Where A and B, RI, R2 and R3 have the indicated meanings;
X is a halogen atom,
subjected to interaction with the compound of the General formula
R4-H,
where R has the indicated meanings, followed by isolation of the target product in free form or in the form of their pharmaceutically acceptable salts.
C "H5 T; S-CH2CH2-C H5 O N CH2 CH2
LiX N-CH2CH7- vx scN-CHjCHj-
@ -OK-snsn2i @KDN CH2CHV
; m-sngsn 13
-CH2CH2Table I
R, R2
- -m-vich
p-R -Rj-CONHN N
i4o
Hto
CH,
Ch.
Ch.
87-89 165-: 66 1 19-121 191-192 228-230
i / 4
238-240
D ng °
-CNG 44-247
-CH -GN2240-241
UZZZZZJ
i 4 2 2
, s Oy-sngsn7i
-ClJ2CH7i7 QN-CH2CH218Ј) N-CH CH219CgH5-NXDN CH2CH7
COC2H5
NC.
20
, cn, "c, HH5 -CHlCHr
C HcS ° HsK -CH CH -. ™ g iS O -0 0
©
2 C6H5-C-N-ON CH2CH
0
26
CeHs-C-N-O-CHiCHf 0
CjHa-CN-CHjCHjr
28C $ Hs - () N-CHaCH229C1- @ H) N-CH7CHZ30F- 0) CN-CH7CHr31HO- I) N-CHZCH2 OE ° 52S -I552i-i
ZZZZ Z ZIJZZLLZ
-Cllj-CHjj-CHj-CH, - 191-192
CH
NY-150
D t °
150-152
I / A Hto3
-CHj154-155
l, 25 Ngo -CHt-CH2115-117
vgo
Ch.
H208-210
S1TS
239-240
Si oh
CH,
HPE-P5
G “L
H197-199
D "t ° J
Ch.
H168-169
CH,
H245-247
H261 -263
D "t ° 3
CH,
H204-J06
H235-236
D H "° J
CH, H200-201
CH, H210-212
i / 2 lyfjCH, H187-1W
36
- ((-NQN-CHaCHj- CJ
37
g) -NQN-CH2CH2Cl
38
OCHZ 0) -NQN-CH, CH2
CH2-NQN-CH2CHr H3CO
C6H5-N0N-CH CH2
41C6H5-NQN CH2CH21, 2HOCH2CH2-MQN-CH2CH2
A3
HOCH2CH2-NQN-CH2CH2 C6H5CH2-NQN-CH2CH2- 45 C6H5-CH2-NQN-CH2CH2A6-O scsn2 C2M502C-NQN-CH2CH248 (RJ-NQN-CH2CHj1 49 C ° Xy) s-n,
CH,
H145-147
i / 2 Hto
H235-236
207-209
i / 2 yoke snay86-89
fl / 5 HtoJCH3H261-263
255-257
G1 z °
CHjH228-230
I200-202
fl, 5 H2oJCH, H193-195
l / 4
H252-254
I
50 (° L-O-cis $ ng
And j
51 —sn7sn2-1
52 O-sngsn, 53SvN5-Sm-SNgSbN5- -sng54
55 QN-SHG
5 CsHs-CX mon
s: С6н5 -нн5СН3
58C6H5-ON-CH7CH7CH259s6n5O-sn2sngsn HC1
60CeHs-CN-0 0 0
61CeHs-CN- 0 ™ 0
62QN-CH2CH7CH2CHa63 (OO-CH2-CNG64CeHs-NQN-SNG-SNGCHjO
45 sneo -) - MO-CH2
CH30
,, snE ° TGGT x1
CHjO- N-CHa-CHj67OKDN CH2CH2
68C6H5 QN-CH2CH2CH /
..5Q93 5 AND ". Stage 1
L1J ..- 41 $ J6
i HgO HH224-225
l Hto CH3H198-200
l / 2
H248-251
CM, H
170-171
i r4o
-CHt-199-200
-CH, 184-185
l HtOJ
194-ijs
i ngo
CH,
112-113
l / 2, N
295-297
l / 2
129-130
l / 2, N
115-117
/ 2
H190-192
CH, H118-124
-CHt-CHt-255-257
CH, H92-96
3/4
H129-130
H263-265
il207-209
69 C "HS-Oi-CH2CH2-CH3
70 (O)
} N-CHrCHa4Ct
71 CfiHrNQ№-CHjCHj
"C.B.HCH2CHNJH fN-CH2CH273
H
t -N-CH2-CH2CH3 n-CnH9-N-CHy-CHj C $ H5 CH3 75 CjHs-CHj-CH-Wz-N-CHj-CHj
U
Cie-C- -MO-Fg-cHgCH3 CH3- -NQN-CHa-CHj§V-NQN-CH2-CHZ
C —NQN — CH2 — CH 2 —CF 3 C 6 H 5 —CH — CH — CH 2 —N QN — CH 2 —CH 7 CH 3 CH2-CH 84
CHj CHjCH3
HO-C- (CH2) (CH2) 2-CH-NQbMCH2lrCH3CH3
85
C -OTCH, 0
86
N-CH, CH, I
I
Continuation of table
f s b
183-184
CHfH
63-65
-CH2-265-267
H121-123
CH3H
f25
CH,
H60-66
CH, H
50-54
CH, H
201-202
CH, HI25-127 (0.5H20)
CH, K185-187
CHj
H85-87
CH, H132-135
SNEN115-120
CHjH95-102
CH,
Hor
CH, I200-202
CHjH187-J 89
87 -CH2-CH288 SQN-CH2-CH,
Ul2-lhj
p-C, g H j-NH-CHj-CH CHjO, CH5
CHjO X 4H2-CH2-N-CHrCH2CH3
(sn5G): ns-sn2-sn2. Hz-MH-CH2-CH293I-Adementyl-NH-CHj-CI j §XD NH CHrcH2CHj
H
0 (JN-CH2-CH W y
sn,
+ QN-CH CH
C6H5-O CH7 CIS C6H5-CHj-N-CH2-CH2NH-CH2-CH2 (Oj -NH-CHj-CHjCHj (yNH-CHj lHCI
CHJ CH3
102
+ Q -NH-CH2-CH2Po TLC, Ch10g (Mprck), layer thickness 0.25 mm, AcOH: EtOAc: MeOH 20: 5: 5, R 0.13
1648250
ig:
„Continued tzRl.1
si
II85-87
sn.
H183-185
sn,
H 123-SH
sn,
Я58-60
CH,
HU9-I50
CH,
11122-126
CHj, 1175-78
Cll, II 39-142
175-177
Cll.
H13-95 (0.5 | 140)
SNE11170-173
CH3II226-228 (, 5HzO /
CH,
H270-271
CH,
H164-185
nineteen
1648250 Rl 2
R rR3-CO-NH
H-U-H.
iH

-
V,
. - -rt-f-n-bat-fi
IIEllIl
i CtHs-QN-CHjCHf10 C | Hs-) cHjCH2O5O-CHz-CH2I
R, R,
RrVc-NH- o -4 o
H
Example
R4-R, 10
) m-snsn2,, 0-ch2-sn2 © - lON-CH2-CH2111 (O-CHfCHtN
112
(OK; N-cHo-CH, 2-v .n2
11 g (5) -NON-CH2-CH2114
@ XjN-CH2-CHr
115
1648250 Rl 2
20
H-U-H. Table
T „m With
CH |
H189-190
H182-183
H154-156
R, R,
Table 3
G R T R4 IT T L
H235-237
H249 (l 0.5)
II300 (X0.5 HZ0)
H250-251 (M HClxl H20)
H260-261 (0.25 Hj.0)
H144-145 (Hi HfO)
CH3H223-226 (0.5)
CHH124-127 (nHClx H.O)

CH5 239-240 No. 20)
H209-212 (xO, 75-H20)
Table 4
23 (patent of Germany U, 0 2304977)

权利要求:
Claims (1)
[1]
Claim
The method of obtaining 6- (acnlamino, aryl) -4,5-dihydro-3 (2H) -pyridazino derivatives of the general formula m = 0.1 or j
c) the group r ₉ -n-ch ₂ -ch ₂ -n6 is oxycarbonyl, C, -C ₂ ~ acylcarbonyl, C ^ -C ^ alkoxycarbonyl, cyano groups or phenyl groups; unsubstituted or substituted with 1-2 halogen atoms, methyl or methoxy group, or mean groups of the formula R RgN—, where R and Rg are the same or different and mean hydrogen, phenyl groups or a C ^ -C ^ acyl, or benzoyl, or benzimidazol-2-one-1-yl residue, "
and Rg together form an chain with C <-C ₂ , or of the general formula
R _r R ₃ -C0NH
NNH where the phenylene radical substituents are relative to each other in the position of meta or steam;
A and B are hydrogen or together form a bond;
Rj is hydrogen or C ^ -C ^ alkyl;
Rg, is hydrogen or R | and together they mean the remainder C _t -C ₂ ~ alkylene, provided that A and B are hydrogen,
R ₃ is C ₍ straight chain C4-alkylene, unsubstituted or substituted with one to two C ^ -Cy-alkyls;
R ^ -a) imidazol-1-yl or
b) a group of the general formula w ⁵ η Ό * Wb * “(CH2) _t where the dotted line means an additional bond;
Ry and Rg * are the same or different and mean hydrogen, C <-C ^ alkyl radicals, unsubstituted or substituted25 where is the Cj-Cj or C | 2 hydrocarbon residue, unsubstituted or substituted by phenyl, unsubstituted or substituted by methoxy, hsterraryl with 5 -6 members of the krelts, which can contain an oxygen atom;
, or the general formula
r)
P = 2,3 group where, R _(o and
e) group
R ₍₍ - hydrogen atoms, hydrocarbon residues. C <-C.2, unsubstituted or substituted with one or two phenyls, or cycloalkyl groups C, -C | 2, unsubstituted or substituted, with phenyl, or adamantyl residues, or benzocondensed cycloalkyl 'groups C ^ -C ^, or the formula (CH ₂ ) _2h
Ί648250 where R and R ^ are hydrogen, halogen atoms, alkyl C <| -C $ or alkoxy radicals C | -C <, or
e) a group of general formula ^{K |} Bj
R15
pd, hydrogen, CIL, or their pharmaceutically-substituted lemma, which is either substituted with C {-C ₄ ~ alkyl, the venom does not mean a group of the formula wherein R ₁₃ or SC-C is a differentiated compound of the general formula acceptable coil with where G - an oxygen or sulfur atom;
R | 4 and R _jy are H or _C. ^ - C ₄ * · alkyl, provided that if Rp R ^, A and B are hydrogen atoms, then R does not mean methylene unsubstituted or substituted by C ^ -C ^ alkyl, and if R _a are hydrogen atoms, then Rf means a hydrogen atom or C ^ -Cj alkyl, Rj means methylene unsubstituted where
XR ₃ -C0NH
A and B, R4, R ^, and EdUnderstand the meanings;
X is a halogen atom, is reacted with Compound A and B with a 20 general formula
R ₄ is H, where R ^ has the indicated meanings, followed by isolation of the desired product in free form or in the form of | pharmaceutically acceptable salts.
προih
Table I
R _t R ₂ p-Rij-Rj-CONH
Example ____________________-_______________ Bn _g oz ----- ------——R . t _l „, ° s 1 2 • 3 L ‘ 5 6
2 (H jC) _a N-CH [1/2 · H ^ oj CH H 74-75 3 (n ₃ s) _g n-sn _g sn ₂ -H H 168-170 4 OKN-CH ₂ CH _g - [1-Η, ρ] CH j H 143-145 5 O-mn-sn ₂ sn _g - [ι, 5 n _g <>] H H 168-170 6^c " ^h 5Qn-ch ₂ ch ₂ -CH H 87-89 7 ; ^With " ^H5 T ^^ ^_CH 2 ^CH 2 · ^;[1 n _g o] H H 165-: 166 8 ^ Zsy-sn ₂ sn ₂ -CH ₃H 1 19-121 $ * §Cn-ch ₂ ch ₂ - ''H H 191-192 10 '(o> - <3 ^ - ^ n _g cn ₇ -CH ₅H 228-230 eleven <2X) n-ch ₂ ch ₂ - [| / 4 N _g o] H H 238-240 12 <§K3n-CH ₂ CH ₂ - [1 V] -CH _Z -2'44-247 thirteen <§HQn-ch ₂ ch ₂ - ¹ -sn _g -sn ₂ -240-241
9 1648250 . 10 Ί ---------------------- - · _Ί —----- Continuation of the table. 1□ '1 ’La________ 14 (q / xQn-CHjCH, --CII _t -CH _e -CH _i -CH _t - 191-192. fifteen . QN-CHjCHf-CH, H 148-150 16 O-ClJjCHr D ^H ° ° J H h 150-152 17 (Zy-CH _g CH ₂ - [l / 4 H _t oj -SI, - 154-135 ‘ 18 (2X-CH _g CH _g - ABOUTfl, 25 H, o] -CH _t -CH ₂ - 115-117 19 C ₆ H ₅ -N-Qn-CH ₂ CH ₂ - coc ₂ n ₅ CH, H 2) 6-217 20 c ^ O-aV "! - M CH, H 208-210 21_{C (} ™ X> ^ T ς .. CH, H 239-240 22^C TiX> ^s ' ^s ' - 'ch, H 113-P5 23 H ’H 197-199. 24 • ' ⁰ ^H ^ ^b C ^K ~ ^CH 2 ^CH 2 ~ [1 H _t oj CH, H 168-169 25 C _B H ₅ -C-S <> - CH ₂ CH ₂ -CH, H 245-247 261 . H h 261-263 27 CsH5-O ^NCH 2 ^CH f [1 H _t o] CH, η 204-206 28 C _s Hj-O-CH ₂ CH ₂ -H, h 235-236 29th C1 - ^ - Qn-CH ₂ CH2- ft H ₄ o] CH, H 200-201 thirty F- © -On-C ^h ₂ CH ₂ - - CH, H 210-212 31 ho-Qn-ch ₂ ch ₂ - [t / 2 H, oJ CH, H 187-188
eleven
1643250
G -------------- .......1 ..... Continue>1> 1 1st table 165 ' 32 ho-Qn-ch ₂ ch ₂ -n n 216-218 33 c ₆ h ₅ ch ₂ ~ Qn-ch ₂ ch ₂ - [1 n _g o] sun ₃n 190-192 34 C, H5CH ₂ -O <- ^s N _g C ⁿ 2Tn n 192-194 35 F - <^ k (> - CH _g CH ₂ -sn _en 223-225 36 ^ -nQ ^N ~ ^CH 2 ^CH 2 ~ ctSt. in 145-147 37 ^ - nQn-ch ₂ ch ₂ - Cl fl / 2 n n 235-236 38 0CH ₃ (o) —nQn-ch ₂ ch ₂ -n n 207-209 39 ^ ch ₂ -nQn-ch ₂ ch ₂ - [l / 2 N _g o] sun ₃in 86-89 H ₃ C0 40 C ₆ H ₅ -nQn-C ^h ₂ CH ₂ - [1/5 N _g 0] sun ₃in 261-263 41 C ₆ H ₅ -nQn-CH ₂ CH ₂ -n in 255-257 42 HOCH ₂ CH ₂ -nQn-CH ₂ CH ₂ - 0 ι ° Ί sn _ein 228-230 43 hoch ₂ ch ₂ -nQn-ch ₂ ch ₂ -n n 219-221 44 CgHsCHj- Ny2 / N ~ CH ₂ CH ₂ ~ [1/4 N _g 0] sn _eAND 178-179 45 . C ₆ H ₅ -CH ₂ -nQn-CH ₂ CH ₂ - . D n _g o] n n 171-173 46 Oc-nQn-ch ₂ ch ₂ - 0 g °] n n 134-136 0 47 C ₂ H ₅ O ₂ Cn (3n-CH ₂ CH ₂ - /. . n and 200-202 48 ^ ' ^N O ^N_CH 2 ^CH 2 ~ 0 .5 N _g o] St. n 1 93-195 ¹ 49 C °) -nQn-ch ₂ ch ₂ - [1/4 H _t 0] n 1n 252-254
tg . . Ί .................. * ’Ί r “; --------- t ... about4 long table ”13.1 6 fifty (° <<> - ^cn ^ ⁿ g ϋ n _g o] H Η 224-225 51 * VJ1-CH ₂ CH ₂ - ' [1 H _t o] CH Η 198-200 52 t + = 1 ^ -sn ₂ sn ₂ - [1/2 11.0 J H Η 248-251 53 C ₆ H ₅ -O-CH ₂ -Cll Η 170-171 54 SvN ₅ -O-sn _g - D '71-c " _t - 199-200 55 O ~ CH ₂ - -CH _t - 184-185 56 c ₆ H ₅ O- ^H is CH,CH Η 200-202 37 CeHsO- ^ iCH [1 H _t oj-CH, - 194-1Μ 58 C ₆ H ₅ O-CH ₂ CH ₂ CH ₂ - [1 H _x oJ CH Η 112-113 . 59 c ₆ h ₅ O-ch ₂ ch ₂ ch ₂ --nHCl [1/2 HjOj Cll Η 295-297 60 c ₆ h ₅ O-ch ₂ ch ₂ ch ₂ ch ₂ - [1/2 H ₂ oJ H Ή 129-130 61 SbN-O ¹ 'CH ₂ CH ₂ CH ₂ CH ₂ - [1/2 H _t o] CH Η 115-117 62 <Qn-ch ₂ ch ₂ ch ₂ ch ₂ - [1/2 H _t o] H Η 1 90-192 63 C °> NCX ^CH 2- ^CH rCh j Η 118-124 64 C ₆ H ₅ -nQN-CH2-CH ₂ - -sn _g -sn, - 255-257 * 65 '· ’^ch a CH ₃ 0 - ^ - NO ^N_cH 2 ~ ^CH r XH ₃ 0 - CH3 Η 92-96 66 CH _s 0 - * ^ 1> N-CH ₂ -CH ₂ - [3/4 H _t 0] H Η 129-130 67 OQn-CH ₂ CH ₂ -H Η 263-265 68 CjH _s »Qn-CH ₂ CH ₂ - CHjH II 207-209
ΞΙT '~ “ Prod;“ΠΊ burning table 16 69^C “ ^H 5 * C ^N_CH 2 ^CH 2 ~ CHf H H 183-184 10 ^ -nQn-CHj-CHjXt Chj H 63-65 eleven C ₆ H ₅ -nQn-CHjCH ₂ --CH _X - 265-267 72 CHj C ₆ H5-CH ₂ CH ₂ -N-CH ₂ CH ₂ - H H 121-123 H 73 t> -N-CH ₂ -CH ₂ - CH ₃ n-CnH ₉ -N-CH ₂ -CH ₂ - CH ₃H 325 74 CH ₃H 60-66 - - C _S H ₅ CHj c ₆ h ₅ -ch ₂ -ch-ch ₂ -n-ch ₂ -ch ₂ - 75 Chj H 50-54 76 cn _e - - ^ -> O * -9H ₂ -sn ₂ - Chj H 232-234 77 CHj W ₃ - ^^ nQn ~ CH ₂ -CH ₂ - Chj H 201-202 78CH H 125-127 ("0.5H ₂ 0) 79 <^ n (3N ^ch 2-CH ₂ - CF ₃Chj H 185-187 80 C ₆ H ₅ -CH- CH-CH ₂ -nQ ^n_ch 2 ^_CH 2 ^_Chj H 85-87 CH ₃ 81 C _in H ₅ -CH-K0Y-CH ₂ -CH ₂ - CH H 132-135 82 c ₆ h ₅ -ch ₂ -ch ₂ -nQn-ch ₂ -ch ₂ - Chj H 115-120 83 СНз-ХЗ ^М ^СН ^2_СН 2 ^_Chj H 95-102 ’ CH _e CH ₃ CHy 84 HO-C- (CH ₂ ) ₃ -C = CH- (CH ₂ ) ₂ - CH-N (jN- (CH ₂ ) _r CH ₃ - Chj H 01 ^xChj 85 0 CH H 200-202 86 JJn-CH ₂ -CH ₂ - CH H 187-189
I 7
1 i ........................ ......]; ··· Pre;p; - - tzbl 1.1 ' 87 O-CH ₂ -CH ₂ - cn ₅eleven 85-87 88 sQn-CH ₂ -CH ₂ - CH H 183-185 89 nC ,, H _M -NH-CH _€ -CH _t - Chj H 123-124 90 0Η ₃ 0γ ^ QHj СНзО - ^ sn ₂ -сн ₂ -ы-сн ₂ -сн _g - Cllj Ή 58-60. 91 CH ₃ (ChS> HN-CH ₂ -CH ₂ - CH H 85-87 92 (-n ^ NH-CHi-CH-r . ch II 149-150 93 I -Adanrantyl-NH-CH ^ -CHj- Cll _sII 122-126 94 - (oX3 ^NH_CH r ^CH 2 CH ₃, H 75-78 95 CHj Op) w-CH ₂ -CH ₂ - Cll II 139-142 CH ₃ 96 -N0Y-CH _g- CHG H H 175-177 97^c 6 ^H 5O ^_CH i ^_CHrCll H 13-95 (lO, 5H _g 1 98 C ₆ H ₅ -CH ₂ -04-CH ₂ -CH ₂ - sn _eH 170-173 99 NH-CHpCHp Chj H 226-228 (> 11IC1 100 (o £> -nh-ch ₂ -ch ₂ - ch II 190-192 101 CHj ~) -NH-CH ₂ * 1HC1 ^CH J CH ₃CH H 270-271 102 + Q ^hNH_CH 2 ~ ^CH 2 ^_CH H 164-185
*
According to TCX, SiO ^ (Merck), layer thickness 0.25 mm, AcOHiEtOAc: MeOH ^J 20: 5: 5, R ^ · 0.13
19 . 1648 250 20
Ri Ri u 1 / ιι T a b l u u a ’2
R <rR ₃ -C0-N11 ^N H
Pr-W ... 1 "♦ -" "-_T v- pr | ° ^c 103 s ₆ N ₅ - <En: n ₂ sn ₂ - CH} H 189-1 90 W C "H5-0 * - ^c H2CH ₂ - H H ) 82-183 ios 0H-CH _G CH _g - H H 154-156
Q Ri R Table 3
RrR _s -c-NH- <o> -4 ^ 0
H
Example PP · ρ ·.)^R < V^T p _L '° ^C ··. ·'. ) 06 @ —O ^ —CH ₂ —CH _g - H H 235-237 ¹⁰⁷ <o> -nOn-ch ₂ -ch ₂ - H H 249 (l0.5 H _± O) 108 @ -Qn-ch ₂ -ch ₂ - H H 300 (X0.5 H ₂ 0) 109 © Q4-CH2-CH2- H H 250-251 (XI HClxl H ₂ 0) 110 @ -On-ch ₂ -ch ₂ - H H 260-26! (x0.25 HjO) eleven! (9> nQn-ch ₂ -ch ₂ - H H 144-145 (xl H _r 0) )12 @ -Qn-CH2-CH ₂ - CH ₃H 223-226 (x0.5 1CO). t 113 © -nQn-CHj-CHj^CH i H 124-127 (xHClxZ H ^ O) 114 <@ - Q ^N ' ^CH 2 ^_CH 2 “ H CH ₅239-240 WIjO) 115 <§HQn-ch ₂ - H H 209-212 (xO, 75-N _g O)
21 1648 250 22
J example vv 1^r <1 f s Table 4 1 ° ^C 116 sn ₃ @ 3n-CH-CH ₂ - CH H 257-260 (K0.5 N _g 0) 117 sn ₃ @ -nQn-CH-CH ₂ - CH H 208-209 118 CHj © -Qn-ch ₂ -ch- CH H 206-207 (xl H ₂ 0) 119 ch ₃ <@ - nQn-ch ₂ -ch- CH 5 H 256-258 120 ch ₃ <oJhnQ ⁿ “CH- CH H 204-206 121 CH ₃ W> -sn ₂ -s- CH ₃CH H 198-199 ("0.5 H _z 0) 122 C ₂ H ₅ <OX) N-CH-; / cn ₃ ^ cn ₃ Ch Ch j eleven 90-95 (Kl H _a 0) 123 CH H 100-102 (XI, 5 H _e 0) 124 n ~ ^C 3 ^H 7 © O-CH- CH ₃H 78-80 (XI, 25 H ₂ 0) 125 nC ₅ H "@o ^ -. CH H 78-80 (KI H ₂ 0) 126 CH ₃ W> CH ₃CH H 203-205
1648 250 24
____ Ta b_: l and a 5Table 6 Example I EC 50% P Example 1 EC 50% Example 1 EC 50% b 0.02 73 1 Substance by Germany patent ί 1 0.01 74 1 No. 2123246 12 0.2 75 0.119 0.05 76 0.01 1 10 20 0.008 79 0.01 c 3 26 0.7 80 0.1 9 5 27 0.02 86 1 eleven 40 29th 0.01 91 0.1 12 6 33 0.02 95 0.144 35 0.002 96 0.434 40 0.003 100 0.1> 46 49 0,03 106 0.00626 51 2 115 0.1> 46 61 0.9 126 0.01 Substance by Germany patent No. 2304977 62 0.3 8 > 100 ¹ 9 > 100 4 - ..... ’Ll 100
Table 7
Example ED 20% - .----------—Example ί ED 20% in. in. at 6. ί century in. b. ! _ ______J______
6 0.1 - 8 0.01 - 22 0.01 - 38 - 0.007 39 0.02 40 * 0.02 51 0.2 '- - 63 - 0.005 65 ', 0.005 -
700.001 71 0.02 - 73 0.1 - 74 - 0.02 75 - 0.02 84 - 0,07 88 0.02 - 95 0,03 - 97 0.05 -
251648250 26Table 8 ' Table 9 Example Units 202 ' Example | ED 0.752in .V. j at 6. 53 0.47 66 3.6 Substances by patent Germany If 2123216 7 / 12 eleven1 ... 99 68 14- 1 115 4.1 201 23I14 (German patent 10 eleven (German patent 1 - * 2123246)2304977) 18 10 - 23 (Germany patent 10.0 No. 2304977)
Compiled by I. Bocharova Editor N. Rogulich Tehred L. Oliinyk Corrector, N. King Order 1417 Circulation 247 Subscription.
VNIIIPI of the State Committee for Inventions and Discoveries at the State Committee for Science and Technology
1 13035, Moscow, Zh-35, Raushskaya nab., D. 4/5 ‘
Production and Publishing Plant Patent ”, Uzhgorod, st. Gagarina, 101

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同族专利:

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法律状态:

优先权:

申请号 | 申请日 | 专利标题

DE19833302021|DE3302021A1|1983-01-22|1983-01-22|6-ARYL-4,5-DIHYDRO-3-PYRIDAZINONE, THEIR PRODUCTION AND USE|

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