Method of producing cyclic derivatives of amine or hydrohalides thereof

专利摘要:
1. Claims for the contracting states : BE, CH, DE, FR, GB, IT, LI, LU, NL, SE New cyclic amine derivatives of general formula see diagramm : EP0224794,P49,F1 wherein A represents a -CH2 -CH2 -, -CH=CH-, see diagramm : EP0224794,P49,F2 or see diagramm : EP0224794,P49,F3 group and B represents a methylene, carbonyl or thiocarbonyl group or A represents a -CO-CO- or see diagramm : EP0224794,P49,F4 group and B represents a methylene group, whilst the atom marked x is linked to the phenyl nucleus, E represents a straight-chained alkylene group with 1 to 3 carbon atoms optionally substituted by an alkyl group with 1 to 3 carbon atoms, G represents a straight-chained alkylene group with 1 to 5 carbon atoms optionally substituted by an alkyl group with 1 to 3 carbon atoms, whilst a methylene group, adjacent to a phenyl nucleus, of a straight-chained alkylene group with 3 to 5 carbon atoms optionally substituted by an alkyl group may be replaced by an oxygen or sulphur atom or by an imino, methylimino, sulphinyl or sulphonyl group, R1 represents a hydrogen or halogen atom, a trifluoromethyl, nitro, amino, alkylamino, dialkylamino, alkyl, hydroxy, alkoxy or phenylalkoxy group, whilst each alkyl moiety may contain from 1 to 3 carbon atoms, R2 represents a hydrogen or halogen atom, a hydroxy, alkoxy, phenylalkoxy or alkyl group, whilst each alkyl moiety may contain from 1 to 3 carbon atoms, or R1 and R2 together represent an alkylenedioxy group with 1 or 2 carbon atoms, R3 represents a hydrogen or halogen atom, an alkyl or alkoxy group with 1 to 3 carbon atoms in the alkyl moiety, or a hydroxy, nitro, cyano or trifluoromethyl group, R4 represents a hydrogen atom, an alkoxy, alkanesulphonyloxy, amino, alkylamino or dialkylamino group with 1 to 3 carbon atoms in each alkyl moiety or an alkanoylamino group with 2 or 3 carbon atoms in the alkanoyl moiety or R3 and R4 together represent an alkylenedioxy group with 1 or 2 carbon atoms, R5 represents a hydrogen or halogen atom, a hydroxy, alkyl or alkoxy group with 1 to 3 carbon atoms in the alkyl moiety, m represents the number 1, 2, 3, 4 or 5 and n represents the number 0, 1 or 2, but n + m must represent the number 3, 4 or 5, the enantiomers, diastereomers and acid addition salts thereof. 1. Claims for the contracting states : AT, ES, GR Process for preparing new cyclic amine derivatives of general formula see diagramm : EP0224794,P54,F1 wherein A represents a -CH2 -CH2 -, -CH=CH-, see diagramm : EP0224794,P54,F2 or see diagramm : EP0224794,P54,F3 group and B represents a methylene, carbonyl or thiocarbonyl group or A represents a -CO-CO- or see diagramm : EP0224794,P54,F4 group and B represents a methylene group, whilst the atom marked x is linked to the phenyl nucleus, a methylene group, whilst the atom marked x is linked to the phenyl nucleus, E represents a straight-chained alkylene group with 1 to 3 carbon atoms optionally substituted by an alkyl group with 1 to 3 carbon atoms, G represents a straight-chained alkylene group with 1 to 5 carbon atoms optionally substituted by an alkyl group with 1 to 3 carbon atoms, whilst a methylene group, adjacent to a phenyl nucleus, of a straight-chained alkylene group with 3 to 5 carbon atoms optionally substituted by an alkyl group may be replaced by an oxygen or sulphur atom or by an imino, methylimino, sulphinyl or sulphonyl group, R1 represents a hydrogen or halogen atom, a trifluoromethyl, nitro, amino, alkylamino, dialkylamino, alkyl, hydroxy, alkoxy or phenylalkoxy group, whilst each alkyl moiety may contain from 1 to 3 carbon atoms, R2 represents a hydrogen or halogen atom, a hydroxy, alkoxy, phenylalkoxy or alkyl group, whilst each alkyl moiety may contain from 1 to 3 carbon atoms, or R1 and R2 together represent an alkylenedioxy group with 1 or 2 carbon atoms, R3 represents a hydrogen or halogen atom, an alkyl or alkoxy group with 1 to 3 carbon atoms in the alkyl moiety, or a hydroxy, nitro, cyano or trifluoromethyl group, R4 represents a hydrogen atom, an alkoxy, alkanesulphonyloxy, amino, alkylamino or dialkylamino group with 1 to 3 carbon atoms in each alkyl moiety or an alkanoylamino group with 2 or 3 carbon atoms in the alkanoyl moiety or R3 and R4 together represent an alkylenedioxy group with 1 or 2 carbon atoms, R5 represents a hydrogen or halogen atom, a hydroxy, alkyl or alkoxy group with 1 to 3 carbon atoms in the alkyl moiety, m represents the number 1, 2, 3, 4 or 5 and n represents the number 0, 1 or 2, but n + m must represent the number 3, 4 or 5, the enantiomers, diastereomers and acid addition salts thereof, characterised in that a) a compound of general formula see diagramm : EP0224794,P55,F1 wherein A, B, E, m and n are defined as hereinbefore, R'1 represents a hydroxy, amino or alkylamino group protected by a protecting group or has the meanings given for R1 hereinbefore and R'2 represents a hydroxy group protected by a protecting group or has the meanings given for R2 hereinbefore, is reacted with a compound of general formula see diagramm : EP0224794,P55,F2 wherein R'3 , R'4 and R'5 have the meanings given for R3 , R4 and R5 hereinbefore but the hydroxy, amino or alkylamino groups contained in the groups R3 to R5 may be protected by a protecting group, and U represents a nucleophilic leaving group such as a halogen atom or a sulphonyloxy group, and optionally any protecting group used is subsequently split off, or b) in order to prepare compounds of general formula I wherein G has the meanings given for Gin claims 1 to 5, with the exception of the groups containing a sulphenyl, sulphinyl or sulphonyl group, A represents a -CH2 -CH2 - group, B represents a methylene or carbonyl group and m + n represent the number 4, a compound of general formula see diagramm : EP0224794,P55,F3 wherein R1 to R5 and E are defined as hereinbefore, G' has the meanings given for Gas hereinbefore with the exception of the radicals containing a sulphur atom or a sulphinyl or sulphonyl group, A' represents a -CH=CH- or -CH2 CH2 - group and B' represents a methylene or carbonyl group, is hydrogenated in a solvent or mixture of solvents, or c) in order to prepare compounds of general formula I wherein B represents a carbonyl or methylene group, a compound of general formula see diagramm : EP0224794,P56,F1 wherein A is defined as hereinbefore, R'1 represents a hydroxy, amino or alkylamino group protected by a protecting group or has the meanings given for R1 hereinbefore, R'2 represents a hydroxy group protected by a protecting group or has the meanings given for R2 hereinbefore, and B' represents a carbonyl or methylene group, is reacted with a compound of general formula see diagramm : EP0224794,P56,F2 wherein E, G, m and n are defined as hereinbefore, R'3 , R'4 and R'5 have the meanings given for R3 , R4 and R5 hereinbefore, but the hydroxy, amino or alkylamino groups contained in the groups R3 to R5 may be protected by a protecting group, and V represents a nucleophilically exchangeable group such as a halogen atom or a sulphonyloxy group, and optionally any protecting group used is subsequently split off, or d) in order to prepare compounds of general formula I wherein A represents a -CH2 -CH2 - or -CH=CH- group and B represents a thiocarbonyl group, a compound of general formula see diagramm : EP0224794,P57,F1 wherein R1 to R5 , E, G, m and n are defined as hereinbefore and A' represents a -CH2 -CH2 - or -CH=CH- group, is reacted with a sulphurising agent, or e) in order to prepare compounds of general formula I wherein A represents a see diagramm : EP0224794,P57,F2 group and B represents a methylene group, a compound of general formula see diagramm : EP0224794,P57,F3 wherein R1 to R5 , E, G, m and n are defined as hereinbefore is reduced in a suitable solvent, or f) in order to prepare compounds of general formula I wherein A represents a -CH2 -CH2 - or -CH=CH- group and B represents a methylene group, a compound of general formula see diagramm : EP0224794,P57,F4 wherein R1 to R5 , E, G, m and n are defined as hereinbefore and A, represents a -CH2 -CH2 - or -CH=CH- group, is reduced in a suitable solvent, or g) in order to prepare compounds of general formula I wherein A represents a -COCO- group, a compound of general formula see diagramm : EP0224794,P58,F1 wherein R1 to R5 , E, G, m and n are defined as hereinbefore is oxidised in a suitable solvent or mixture of solvents, or h) in order to prepare compounds of general formula I wherein G has the meanings given for G hereinbefore with the exception of the radicals containing a sulphur atom or a sulphinyl or sulphonyl group, A represents a -CH2 -CH2 - group and B represents a methylene or carbonyl group, a compound of general formula see diagramm : EP0224794,P58,F2 wherein R1 to R5 , E, m and n are defined as hereinbefore, G' has the meanings given for G hereinbefore, with the exception of the radicals containing a sulphur atom or a sulphinyl or sulphonyl group and B' represents a methylene or carbonyl group, is hydrogenated in a solvent or mixture of solvents and subsequently, if desired, a compound of general formula I thus obtained wherein R1 and/or R3 represents a nitro group is converted by reduction into a corresponding amino compound of general formula I, or a compound of general formula I thus obtained wherein R4 represents a hydroxy or amino group is converted by acylation into a corresponding alkanesulphonyloxy or alkanoylamino compound of general formula I, or a compound of general formula I thus obtained which contains at least one chiral centre is resolved into its diastereomers or into its enantiomers and/or a compound of general formula I thus obtained is converted into the acid addition salts thereof, particularly its physiologically acceptable acid addition salts with inorganic or organic acids.
公开号:SU1442073A3
申请号:SU864028479
申请日:1986-11-11
公开日:1988-11-30
发明作者:Псиош Манфред；Хейдер Иоахим；Бомхард Андреас；Рейффен Манфред；Хауэль Норберт；Нолл Клаус；Нарр Бертольд；Лиллие Кристиан；Кобингер Вальтер；Деммген Юрген
申请人:Др.Карл Томэ Гмбх (Фирма)；
IPC主号:

专利说明:

11442073
The invention relates to methods for the preparation of new cyclic amine derivatives of the general formula
.KN,) w.

N-G
-2 amd in n s and in a m l
)P ()
groups,,,
-sn -co-; i
methylene or thiocarbonyl OH
I group -CO-CO- and -CH-CO-,
X
R -
E g
IR, R. R. methylene, and the atoms with the letter X are bound to a phenyl drom-,
Cd-Cg, -alkylene, C, -C-alkylene, with one methylene group bound to the phenyl core may be replaced by an oxygen atom of each C, -C-alkoxy group or. Together form a methylendoxy group}
hydrogen, halogen, C-C-alkyl or C e-alkoxygroup, hydroxy, nitro or trifluoromethyl group, hydrogen, C-C-alkoxy, amino, methanesulfonyloxy or acetylamino-Sr or Rg and R4 together form a methylenedioxy groupJ hydrogen, halogen xy of alkoxy-, 1-5;
0-2, and the type should be the numbers 3, 4 or 5, the SHI of their hydrohalogenide} with the ability to reduce the frequency of cardiac abrasions.
The purpose of the invention is to develop on the basis of known methods a method of teaching new cyclic amine derivatives with a valuable pharmacological property — the ability to reduce the heart rate along with a weak lowering blood pressure. The effect is at low toxicity.
Example 1. 3- t N- - (3,4 dimethoxyfensh I) -ethyl pshleridine-3-yl) methyl-, 8-di (etoxy-1, 3, 4,5-tetrahydro-2H-3- hydrochloride hydrochloride) Benzazepin-2-one, A mixture of 6.37 g (0.020 mol) 3- (piperidin-3-yl) methyl-7, 8 dimethoxy -1.3.4, 5-tetra1 Idro-2H-3-brn azepin P
-
0
five
0
0
five
-2-it, 5.6 ml (0.040 mol) of trietcpamine and 4.90 g (0.0020 mol) of 2- (3,4-dimethoxyphenyl) ethylbromide are heated under reflux for 2 hours, and having At the beginning of the suspension, the solution turns into a clear ane solution, which after about 30 minutes begins to precipitate as a gel. The cooled reaction mixture is dissolved in a mixture of 2 M sodium hydroxide and methylene chloride. The organic phase is separated, washed with water, dried with magnet sulfate, evaporated in vacuo, first purified 800 g of alumina (neutral, activity II-III) using methylene chloride, and then with ethanol (up to 2%), dissolved in acetone and adding methanol hydrochloric acid is obtained hydrochloride.
The yield of 6.2 g (59.7% of theoretical), so pl. 218-219 C.
Calculated,%: C 64.79; H 7.57; N 5, .40.
Found,%: С 64.88j Н 7.55; N 5.21. .
PRI mme R 2. Hydrochloride 3- | (N- - 3- (4-amino-3,5-dibromophenoxy) propyl-piperidin-3-yl} -methyl i-7,8-dimethoxy- 1,3,4,5-tetrahydro-2H-3-benzazepin-2-it is obtained analogously to example 1 from 3- (piperidin-3-yl) -7,8-dimethoxy-1 3,4,5-tetrahydro - -2H-3-benzazepin-2-one and 3- (4-amino-3,5-dibromophenoxy) propyl chloride.
Yield 20.4% of theoretical, mp, 05 ° C (decomp.).
Calculated,%: C 49.99; H 5.48;

, 40 N 6.35 | Br 24, 15; Found,%: C 5.83; Br 24.00, Example 3,
49.12; H 5.80;
45
50
N,
Hydrochloride - (3,4-dime-xyphenyl) -e-thyl-fliperidine-3-yl) -methyl-7,8-methylenedioxy--1,3,4,5-tetrahydro-2H-3-benzazepine- -2-it is obtained analogously to example 1 of 3-C (piperidin-3-yl) -methyl-7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one and 2- (3, 4-lkmethoxy-phenyl) ethyl bromide.
Output 31.7% of theoretical, 142-143 ° C.
C, 64.47;
55
m.p.
Calculated, N 5.57 ..
Found% N
7
7.01; .17;
C, 64.36; H 5.42.
PRI me R 4 Hydrochloride 3-N- (3, 4-dimet to k s ib e n z i p) - i and p h m i sh, 3 31442073
-yl-methyl; -7,8-methylenedioxy-1,3,4, 5-tetrahydro-2H-3-benzazepin-2-it is obtained analogously to example 1 of 3-t (piperidin-3-yl) -methyl -7 , 8-methylenedioxy-1, 3, 4, 5-tetrahydro-2H-3-benzazepin-2-one and 3,4-dimethoxybenzyl chloride.
The output of 30.7% of theoretical so pl. (different).
Calcd.,%: C 63.68; H 6.80; N 5.73.
Found,%: C 3.45, H 7.02; N 5.41.
Example 5. Hydrochloride | g- (2-Phenyleth) N-yl-J-Me-, 8-dimethoxy-1,3,4,5-tetra- gndro-2H-3-benzazepin-2-hydrochloride according to example 1 of 3- (psh1eridin-3-yl) -met t. . Example 8. Hydrochloride 3- / HGN - (4-methoxy-phenyl) -propyl-piperidine-3-Sh1} -methyl / -7,8-di7 etoxy-1,3, - 4,5-tetrahydro- 2K-3-beisazepin-2-it is prepared as in Example 1 from 3- (piperidine-3-yl) -methylJ-7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benz- azepin-2-one and 3- (4-methoxyphenyl) -0-propyl bromide.
Output 29.4% of theoretical, so pl. 215-218 C.
Calculated,%: C, 66.85; H 7.81; N 5.57.
Found,%: C 66.67; H 7.65; N 5.53.
PRIOR 9. Hydrochloride 3- / fN- - 2- (4-methoxyphenyl) -ethyl-piperidine-3-yl-methnl / -7,8-dimethoxy-1,3,4,5 "vMA" - “-Rt rr -
. - - vv-rw - / - -yl-methyl / -7,8-dimethoxy-1,3,4,5til-7, 8-dimethoxy-1,3,4,5-tetrahydro-2o tetrahydro-2H-3 -benzazepin-it semi-2H-3 benzazepin-2-mon and 2-A "nmgt-h ... -.-
G-.,, .- .1- .. “V
ro-2H-3 benzazspin-2-one and 2-phenyl ethyl bromide.
The output of 43.5% of theoretical, so pl. 241-243 s.
Calculated,%: C 63.03; H 7.69; N 6.10.
Found,%: C .39; H 7.89; N 6.36.
EXAMPLE 6 Chrichloride 3 - / {N- - 2- (3-nitro-4-ace 1.. aminophenyl) - -ethyl I -piperidin-3-gyl-metn / 7,8-di - methoxy-1, 3, 4, 4-teto-1 and hydro 2H 3-benzazepine-2-oia are prepared according to Example 1 of 3-C (piperidine-3-ip); 1L-7,8-di-methoxy-1, 3,4,5-tetrahydro-H-3-benzazepin-2-one and 2- (3-nitro-4-acetaminophenyl) -3 ethyl bromide.
thirty
".Ch ..... jnci saw
Analogously to Example 1 of 3-G (piperidin-3-Cl) -methyl 7,8-dimethoxy-. 1,3,4,5-tetragvdro-2H-3-benzazepin-2-one and 2- (4-methoxyphenyl) ethylbro 25 MFA.
The output of 19.8% of theoretical, so pl. 227-230 C.
Calculated,%: C, 66.31; H 7.63; N 5.73.
Found; %: C, 66.46; H 7.57; N 5.73.
Example 10. Hydrochloride 3- / tN- - / 2- (4-nitrophenyl) -ethyl-piperidine-3-yl} -methyl / -7,8-dimethoxy-1,3,4,5-tetrahydro-2H -3-benzazepin-2-oia is prepared as in example 1 from-3- (piperidine-3-yl) methyl-7,8-dimethoxy-1, 3,4,5-those trahydro-2H-3-benzazepine -2-it and 2- (4-nitrophenyl) ethyl bromide.
Yield 22.3% of theoretically; m.p. (different).
Calculated,%: C 59; 94; F. N 9.99.
Found-. : from 59.92; H 6.77: N 9.98.
When m e p 7, 3- / fN- 2- (3,4,5-trimethoxyphenyl) ethyl-pyperidin-3-yl-methyl / -7,8-dimethoxy--1,3,4, hydrochloride, 5-those trahydro-2H-3-benzazepin-2-it is obtained analogously to example 1 of 3- (piperncin-3-yl) methyl-7,8-dimethoxy-1,3,4,5-tetragamide 2H-3-benz-azepin-2-one and 2- (3,4,5-trimethoxyphenyl) ethyl bromide.
The output of 22.6% of theoretical, so pl. 135-137 0.
Calculated,%: C 63.53; N. 7.53, N 5.10.
Found,%: C 63.50; H 7.82; N5.09.
Example 8. 3- / HGN- - (4-methoxy-phenyl) -propyl-piperidine-3-Sh1} -methyl / -7,8-di7 etoxy-1,3, - 4,5-tetrahydro hydrochloride -2K-3-beisazepin-2-it is obtained analogously to example 1 of 3- (piperidine-3-yl) -methylJ-7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benz - azepin-2-one and 3- (4-methoxyphenyl) - -propyl bromide.
Output 29.4% of theoretical, so pl. 215-218 C.
Calculated,%: C, 66.85; H 7.81; N 5.57.
Found,%: C 66.67; H 7.65; N 5.53.
PRIOR 9. Hydrochloride 3- / fN- - 2- (4-methoxyphenyl) -ethyl-piperidine-3-yl-methnl / -7,8-dimethoxy-1,3,4,5 "vMA" - “-Rt rr -
- -yl-methyl / -7,8-dimethoxy-1,3,4,5 tetrahydro-2H-3-benzazepin-one is obtained by ... -.-
2o tetrahydro-2H-3-benzazepin-it was obtained ... -.-
thirty
0
g
".Ch ..... jnci saw
Analogously to Example 1 of 3-G (piperidin-3-Cl) -methyl 7,8-dimethoxy-. 1,3,4,5-tetragvdro-2H-3-benzazepin-2-one and 2- (4-methoxyphenyl) ethylbro 25 MFA.
The output of 19.8% of theoretical, so pl. 227-230 C.
Calculated,%: C, 66.31; H 7.63; N 5.73.
Found; %: C, 66.46; H 7.57; N 5.73.
Example 10. Hydrochloride 3- / tN- - / 2- (4-nitrophenyl) -ethyl-piperidine-3-yl} -methyl / -7,8-dimethoxy-1,3,4,5-tetrahydro-2H -3-benzazepin-2-oia is prepared as in example 1 from-3- (piperidine-3-yl) methyl-7,8-dimethoxy-1, 3,4,5-those trahydro-2H-3-benzazepine -2-it and 2- (4-nitrophenyl) ethyl bromide.
The output of 66.8% of theoretical, so pl. 239-245 0.
Calculated,%: 61.91; H 6.80; N 8.34.
Found,%: C 62.25; H 6.66;
N 8.23.
Example 11. Hydrochloride 3 - / {N- (3-metshphenyl) -ethyl} -piperchdin-3-yl} -methyl / -7,8-dimethoxy-1,3,4,5--tetrahydro-2H- 3-benzazepin-2-it is prepared analogously to example 1 of 3 3- (piperidium-3-yl) -methyl 3-7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine -2-it and 2- (3-methylphenyl) ethyl bromide.
Output 38.1% of theoretical, so pl. 234-237 p.
Calcined,%: C 68.55 H 7.88, N 5.92.
five
Found,%: C 68.68; H 7.87; N 6.14.
PRI mme R 12. Hydrochloride (3-labels siphenyl) -ethyl-j-piperidium - 3-yl-methyl / -, 8-dimethoxy-1, 3, 4, 5-tetrahydro-2H- 3-benzazepin-2 - it is prepared analogously to example 1 of 3-1 (p Sheridin-3-yl) methyl-7,8-dimethoxy- (, 3,4,5-tetrahydro-2H-3-benzase pin-2-one and 2- (3-methoxyphenyl) ethyl bromide.
The output of 23.7% of theoretical, so pl. 199-202 °: ..
Calculated,%: C, 66.31; H 7.63,
N 5.73,
Haideno,%: C 66.61 K 7.59 K, 91 /
p H - e.; j, gigg; 0chloride,,. J J- (4-g.thylphenyl) -ethyl)} - gshperid:; p-3-yl) -methyl / -7,8-di etoxy--;, 3s:., Tetrahydro-2H -3-benzazepine 2-it is obtained from example 1, from 3- (pi ergdin-3-yl) -methyl} -7,8-dimethoxy 1,3; 4, 5-tetrahydro-2H-3-benzasega-1n 2-one and 2- (4-methylphenyl) ethyl bromide,
The output of 34.7% of theoretical, so pl. 233-236 ° C.
Calculated,%: C 68.55; H 7-, 88; N 5.92.
Found,%: C 68., 30; H 7.89; N 5.84.
il p and mep 14. Hydrochloride id
, (3-bromfe p-m) -propyl.J piperid, in-3-yl} -methyl / -7 5 8 dyne current si-1,3 ..}., 5-tetrahydro-2H 3-benzazepine 2-she. is prepared analogously to example 1 of 3- (piperidin-3-yl) -methylJ 7,8-dimethoxy-1,3,4,5-tetrahydro 2 H-3 - benzazepin-2-one and 3- (4 brompheyl) pro propyl bromide
 The output of 34.8% of theoretical, so pl. 100-104 S.
Calculated,%: C 58.75. H 6.751 N 5.08; Br 14.48.
Found,%: C 58.40 H 6.66; N 4.79; Br 14.21.
PRI me R 15. Hydrochloride - 2- (3,4-dimethoxyphenyl) ztilz-g1I1 and RVDIN-2-IL-ethyl-2 / -7, 8-dime toxi- --1 53,4,5- tetrahydro-2H-3-benzazepip--2-it is obtained analogously to example t from 3- {piperidine-2 yl) -ethyl-2 -7,8-dimethoxy-1,3,4,5-tetrahydro-2H -3-benzazepin-2 it and 2- (3,4-d w {etoxyphenyl) -ethi.g1 bromide.
The output of 23.8% of theoretical, So pl, 113-115;.
0
0
45
bb
Calculated,%: C 65.33; H 7.75; N 5.26.
Found%: C 65.11-H 7.67f N 5.04.
Example 16. Hydrochloride 3 - / {1 -G2- (35 4-dimethoxyfeicl) et ch-hexa-hydroazepic-3-yl-methyl / -758-limeroxy-1,3, 4,5-terahydro-2H 3-b8nzaz-- pin-2-she „
660 mg (2 μmol) 3-SShexahydroazepin-3-yl) meth1 1G 1-7, P.-dimethoxy-, 35455 tetrahydro-2H 3 benzzeg.in-2 - it and 540. mg (2.2 μm ) 2- (3, ii-dimethoxyfvnil) -ethyl bromide in 3 ml of triztilamine for 1 hour under a condenser of reflux condenser, Reakdionku; cool the mixture and absorb it in methylene chloride and 2 M lye liquor. The alkaline phase is separated and shaken twice with methylene chloride. The combined organic phases are dried over magnesium sulphate and concentrated in vacuo and by chromatography on a column of g, 100 g of alumina (activity II, eluent: methylene chloride — 0.3% ethanol). The resulting fractions are concentrated in vacuo, the residue is dissolved in acetone and the hydrochloride is precipitated with simple ether hydrochloric acid.
Output 600 mg (56.3% of theoretical), so pl. 1b4-1b5 ° C.
Calculated,%; C 65.33; H 7.75; To 5.25,
Found,% s C 65,12; H 7.59; N 5.22.
PRI me R 17, Dihydrochloride 2 - / g N-3 - (4-amcn - 3, 5 - d ib R omfe to K - he) -propyl hexahydroazepin-3-yl - methyl / -7., 8 d1-ketoxy-1, 3, 4,5-tetra-. | hydro-2H-3 benzazepin-2-it is obtained analogously to example 16 of 1.2 g
(3 „6 μmol) (hexahydroazepin-3-ip) -methyl-7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzaz-n-2-one; and 1.36 g (3 , 96 μmol) of 3- (4-amino-3, 5-dibromophenoxy) -propyl chloride with 5 ml of triethyl tylamine.
- CODE 350 mg (13-, 7% of the theoretical-: - :: /.-, -l: l.; -G:} 7:
BYCH:.; Slen, I: S. i / ,.:.; :. ,, -,.; N / 2.42; Вг 5.36.
Found,%: With 47,40; il 5.86; N 22.22; Br 5.49,
PRI m e 1 18, P-g-gppr-J-; ; - --12- (3,4-methylende: oxyphenyl, ;;; ggi, - J-; -piperidin-3-yl} -methyl / -7 ,, 7,.:; - dioxy-1,3 , 4,5-tetrahyd 1H, -: h; -3-protein-azepin-2, it is obtained analogously peg; measure 1 of 3-X {piperid-3-yl) -methyl 7-7.8 methylennoxy-1 , 3,4,5-tetrahydro-2H-3-benzazepin-2-one and 2- (3,4-methylenedide-xyphenyl) ethyl bromide.
Output 85.7% of theoretical, so pl. 234-235 C.
Calculated,%: C 66.73} H 6.03} N 5.99.
Found,%: C 66.58; H 6.31 $ N 5.94.
Example 19. Hydrochloride - (3,4-dichlorobenzip) -piperidin-3-yl J- -methyl | -7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one prepared analogously to example 1 of 3-C (piperidinyl-3-Sh1) -metsch1 j-7,8-Me-tylenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one and 3, 4-dichlorobenzyl chloride.
Output 802 from theoretical, so pl. 240-242 C.
Calculated,%: C 57.90, - H 5.49; N 5.63.
Found: C, 57.77; H, 5.35; N, 5.46.
PRI me R 20. (3-methoxyphenoxy) -propyl-piperidin-3-yl} - -methyl / -7,8-methylenedioxy-1,3,4,5--tetrahydro-2H-3- Benzazepin-2-he is prepared analogously to example 1 of 3- - (piperidin-3-np) -metr-7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3- -benzazepin-2- she and 3- (3-methoxyphenoxy) propion chloride.
Output 42% of theoretical, so pl. 135-138 C.
Calculated,%: C 64.46; H 7.0lj N 5.57.
Found, Z: C 64.46j H 7.02-, N 5.57.
PRI me R 21. Hydrochlor d 3- / fN-3- (3-methylphenoxy) -propyl J-piperidine-3-yl} -methyl / -7.8 meg 1 tsnidnoxy-1, 4, 5-tetrahydro-2H-3-6e; a 2-β-ohm sshc is prepared as in Example 1 from 3-C (piperidin-3-yl) -methyl-7,8-methylenedioxy-1,3,4,5- tetrahydro-2H-3-benzazepin-2-one and 3- (3-methylphenoxy) propyl chloride.
Output 34% of theoretical, so pl. 122-124 ° C.
Calculated,%: C 65.36j H 7.32 $ N 5.65.
Found,%: C 65.01} H, 7.61; N 5,64.- Example 22. 3- / fN- 2- (4-amino-3,5-dich} torfennl) hydrochloride, ethyl} -piperidine-3-nl-methyl / -7,8-dimethoxy -1, 3,4,5-tetrahydro 2H-3-benzaze-pin-2-it is obtained analogously to example 1 of 3-G (piperidine-3 III) -methyl - -7,8-dimethoxy-1,3,4 , 5-tetrahydro-2H-3-benzazep {t-2-one and 2- (4-amino-3,5-dichlorophenyl) ethylbromide romide.
Output 6C% of theoretical, so pl. 137-140 C.
Calculated,%: C 57.03; H 5.58; N 6.98.
Found,%: C 57.27; H 5.82 j N 6.59.
PRI me R 23. SZ- (3,4-methylenedioxyphenoxy) hydrochloride - Propro. drank} -% iperidin-3-Sh1} -methyl / -7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3- -benzazepin-2-ona is prepared in a similar manner to Example 1 from 3- HSpiperidin-3-yl) -methyl-7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one and 3- (3,4-methylenedioxyphenoxy) -propyl-: chloride.
Output 39.9% of theoretical, so pl. 127-129 s.
Calculated,%: C, 62.92; H 6.43; N 5.42.
Found,%: C 62.98; H 6.41-, N 5.05.
EXAMPLE 24 3- / fN-C4- (4-methoxyphenyl) -butyl-piperidin-3-yl} -methyl (-7, -8-methylenedioxy--1,3,4, hydrochloride) hydrochloride 5-tetrahydro-2H-3-benzazepin--2-one is prepared as in example t from 3- (piperndin-3-yl) -methyl-7.8-methylenedioxn-1,3, t ;, 5- tetrahydro-2H-3-benzazepin-2-one and 4- (4-methoxy-uphenyl) -butyl bromide.
Exit 42% of .Topee4Efcoro, t. Pl.
158-163 S.
Calculated,%: C 67,12; H 7.44; N5.59.
Found,%: C, 66.98; H 7.27; N 5.51.
Example 25. -G2- (4-methoxy-phenyl) -ethyl-piperidine-3-un-methyl / -7,8-methylenedioxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2- hydrochloride - it is received analogously to example 1 of 3-.Kpiperidin-3-Sh1) -methyl-7,8-me-typenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one and 2 - (4-methoxyphenip) -ethshleene chloride in dimethylformamide - potassium carbonate at 120 C.
55
The output of 55.6% of theoretical, so pl. 226-228 0.
Calculated,%: C 66.02; H 7.03; N 5.92.
91
Found,%: C 66.18; H 7.03; N 5.87.
PREMIUM Hydrochloride K - (2-phenoxy) -ethyl 1-pnpsridin-3-yl-methyl / -7,8-methylenedioxy-1,3, 4,5-tetrahydro-2H-3-benzazepin-2-she is obtained analogously to example 1 from 3- (piperidin-3-yl) -methylJ-7,8-methylenedioxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one and 2-fepoxyethyl bromide.
The output of 55.7% of theoretical, so pl, 124-127 C.
Calculated,%: C 64.16 N N.6.10.
Found,%: C 64.42-H 7.02; N6.14.
EXAMPLE 27 (4-methoxyphenyl) -ethyl-piperidine-dyn-2-yl | -eth-1-2 / -7,8-methylenedioxy-1 hydrochloride. 3 ,, 4, 5-tetrahydro-2H-3-benzase pin, it receives, analogously to example 1, from 3- (piperidin-2-yl), - etkl 2 -7, 8-metsh7-dioxy-1,3,4-, 5- tetrahydrate - ro-2H-3 benzazepin-2-one and 2- (4-metroxyphenyl) ethyl bromide.
The output of 34.6% of theoretical, so pl. 110-115 ° C.
Calculated,%: C 66.58, H 5245 N 5.75.
Found,%: C, 66.50; H 7J8; N 5.70.
Pr 28, Hydrochloride 3- / L- (4-methoxyphenyl) methyl-piperid1-: n-2-yl. -Ethyl-2 / 7.8 methylenedioxy-si-1,3,4,5-tetra1 idro 2H-3-benzaeepin-2, it is obtained similarly to the PrSH-ger 1 from 3- (piperidin-2-yl) -ethyl-2.- -7,8-methylenedioxy-1,3,4,5-tetragnd - ro-2H-3-benzazepin-2-one and 4-methoxy benzyl bromide,
Output 52% of theoretical, t, pl 148-152 with.
Calculated,%: C 66.02 j H 7.03,
N 5.92.
Found,%: C 65.90; H 7.10 | N 5.98,
Example 29. Hydrobromide, 3- / N- (3-, 4-dimethoxyphenyl) -methyl - -piperidine 2 yl - ethyl-2 / -7, 8-methylene dioxy-1,3,4, 5-tetrahydro-2H -3-benzazepi 1-2-it is prepared analogously to example 1 from 3-C {piperidin-2 yl) -ethyl-2 -7,8-methylenedioxy-1,3,4,5-tetra gvdro-2H-3 -benzazepip-2-bna and 3 ,, Mb current of bebe from il R I) mi yes.
The output of 27% of theoretical, so pl. 138-140 ° C.
7 3I O
Calculated,%: C 59.23; H 6, N 5.11. /
Found,%: C 59.40; H 6.49; N 5.23. .
PRI me R 30, Hydrochloride 3- / if - - 2 - (4-nitrophenyl) -ethyl J-piperidine-2-yl} -til-2 / -7,8-methylenedioxy-1,3 , 4., 5-tetrahydro-2H-3-benzazepin-2-one is prepared as in Example 1 from 3- (piperidin-2-yl) ethyl-2 -7.8-methyestondioxy, 3,4,5 -tetrahydro-2H- -Z-bekzazepin-2-one 2- (4-nitrophenyl) ethylbromide.
Yield 22% of theoretical; t, us: 130-132 0.
Calculated: S% g C 62.20 H 6.43; K 8.37.
Found %: C, 62.16; H 6.57; N 8.37,
PRI me R 31. Hydrochloride 3- / H - 2- (3-trifluoromethylphenyl. P) -e-tyl 1-pipet-RNtsch; -3-yl) -methyl ./- 7, 8-dimethoxy-1 ,, 3,, 4,5 -tetrahydro-2H-3 - benzazepin-2- -one and 2- (3-trifluoromethylphenyl) -ethyl. bromide.
Output 32% of theoretical, t.) T with 150 ° C (decomp.)
Calculated,%: C, 61.53; H 6.50; To 5.32.
Found,%: C 61.70; H 6.42; N 5.27.
The value of Rf is 0.36 (with an impure methylene chloride - methanol 10: 1).
 PRI me R 32, Grvdrokhlorid (3,5-diketoksifenoxy) -propyl 1 - - P4-teridkn 3 yl | -methyl / - 7. B-meter-chenoxy-1,3, 4,5-tetrahydro-2 {1-3-ben-azepin-2-it is obtained in example 1, CK 3- (piperidin-3-yl) -methyl: - -7,8-methylenedioxy-1,3,4,5 tetrahydro-2H-3 benzazepin-2-one and 3- (3,5-dimethoxyphenoxy) propyl chlorochd.
The output of 46.4% of theoretical, so pl, 102-107 ° C
Calculated,%; C 63.09; H 7.00-, N5.25.
Found,%: C 62.96; H 6.86 N 5.50.
PRI me R 33, Hydrochloride - (2-phenylethyl) -piperidin-2 - nor-ethyl, 8-dimethoxy-1., 3,4, Z-gc. trapdose-PO-2H-3-benzazepin-2-it is prepared analogously to example 1 of 3-, piperidin-2-yl) ethyl-2-7, 8 -JIMMVI pc; h {-2H-3-benzazepin- 2-oEia and 2 - f 1g.ggm il bromide.
Yield 37% of the theory rtiMfi (11;, t, pl, 130-132 ° С.
N
BbiMHCJKiHo,%: C 68.53; H 7.88; 5.92. Found,%: C 6B, 42, H 7.97,
N
ten
5.75 ..
II p and me er FOR. Hydrochloride -t3- (4-methoxyphenyl) -propyl-piperidin-2-yl) ethyl-2 / -7,8-dimethoxy-1,3, 4,5-tetrahydro-2H-3-beta 1 zazepin-2 -one is prepared analogously to example 1 of 3-G (piperidin-2-yl) -ethyl-2J-7,8-di-methoxy-2H-3-6-enzazepin-2-one and 3- (4-metoxyphenyl) - propyl bromide.
The output of 43% of theoretical, t 109-112 C.
Calculated,%: C, 67.36; H, 7.99; N, 5.42.
Found,%: C 67.19, - H 7.88} N 5.38.
pl
PRI me R 38. Hydrochloride 3 - / (N- -G2- (4-methylphenyl) ethyl 1-piperidine--2-yl} -ethyl-2 / -7,8-imtoxy-1, 3,4 , 5- -tetrahydro-2H-3-Clyenzazepin-2-it is prepared analogously to example 1 of 3-f (piperidin-2-yl) -til-2-1-7,8-di-methoxy-2H-3-benzazepine -2-she and 2- (4- -me tylphenyl) -e tittbromid.
Output 23% of theoretical, so pl. 109-11GS.
%: C 69.04; And 8.07;
15
C 68.84, H 7.90,
Calculated N 5.75.
Found,%; N 6.03.
Example 39. Hydrochloride - 2- (3-methoxyphenyl) -ethyl} -piperidine Example 35. Hydrochloride-3- / N-20 -2-yl} -ethyl-2 / -7,8-dimethoxy-1,3,4 , 5- -G2- (3-metsh1phenyl) -ethyl-piperidine - tetrahydro-2H-3-benzazepin-2-one-.
-2-yl} ethyl-2 / -75 8-dimethoxy-1, 3,4,5-luchampot, similarly, as-iepy 1 from tetrahydro-2H-3-benzazepin-2-one3- (piperidin-2-yl) -ethyl-2 -7,8-dipole analogously to example 1 of 3 (piperidin-2-yl) -til-2 -7,8-dimethoxy-2H-3-benzazepin-2-one and 2- (3- methylfe - CL) -ethyl bromide.
and 2- (3methoxy-2H-3-bezazazepin-2-one 25-methoxyphenyl) ethyl ethyl.
The output of 25% of theoretical, so pl. 125-127 ° C.
Yield 31% of theoretical, mp; 124-126 ° C.
Calculated N 5.75.
Found,%;
li C 69.04 H 8.07i C 68.9 U H 7.69;
N 5.72,
PRI me R 36. Hydrochloride - 2- (4-methoxy-phenyl) -ethyl-piperidin-2-yl-ethyl-2 / -7.8 dimethoxy-1 H, - 4,5-tetrahydro-2H- 3-benzazepin-2-it is prepared analogously to example 1 from 3- (piperidin-2-yl) -ethl-2 -758-dimethoxy-2H-3 benzazepin-2 it and 2- (4--methoxyphenyl) -ethyl bromide.
The output of 48% of theoretical, so pl. 112-114 0.
Calculated,%: C, 66.85; H, 7j81j N, 5.57.
Found:% C, 66.69; H, 7.86; N, 5.65. .
PRI me R 37. Hydrochloride-G2- (4-nitrophenyl) ethyl-piperidine35
45
EXAMPLE 40. 3 -./t2 hydrochloride (3, 4,5-trimegloxyphe} ish) -ethyl-per1adin-2-yl-etsh1-2 / -7,8-dimethox 1 -15 ZU 4 , 5 - tetra-2H-3-benzazepine 2-eye get; analogue to Example 1 of 3- (piperidin-2-yl) -eth-I-2} -75 8-diketox-2H-3-benzazepin-2-one and 2- (3,4 W-trimethoxyphenyl-ethyl-Sfomda.
Lift 15% of theoretical, mp 138-140 ° C.
Calculated,%: C 63.98; H 7.70; N 4.97.
Found,%: C 63.74; H 7.55; N 4.65.
EXAMPLE 41 (2-Fluorophenyl) -e-tyl-piperidine-1-3-yl} -methyl / -7,8-dimethoxy-1,3,4,5 hydrochloride
-2-yl) ethyl-2 / -7,8-dimethoxy-1,3,4.5-k.o-tetrahydro-2H-3-benzazepin-2-one and
vJV. -t-tetrahydro-2H-3-benzazepin-2-it is obtained similarly to npiiMepy 1 from 3- (piperidin-2-yl) -til-2- -758-dimethoxy-2H-3-benzazepin-2 it and 2- (4-nitrofenil) -ethyl bromide.
Output 8% of theoretical so pl. 126-128 C.
Calculated,%: C 62.59, H 7.00 N 8.11.
- (2-fluorophenyl) ethyl bromide.
Yield 49% of theory, mp
210 C.
55
Calculated,%: C 60.82; H 6.87; C, 60.88; H 6.73;
5.46,
Found% 5.60:
Rg value
g 0.33 (ci-shica gel, methylene chloride - methanol 10: 1).
ten


42073
Found,%: C 62.56; 11 6.91, N 8.16.
PRI me R 38. Hydrochloride 3 - / (N- -G2- (4-methylphenyl) ethyl 1-piperidine--2-yl} -ethyl-2 / -7,8-imtoxy-1, 3,4 , 5- -tetrahydro-2H-3-Clyenzazepin-2-it is prepared analogously to example 1 of 3-f (piperidin-2-yl) -til-2-1-7,8-di-methoxy-2H-3-benzazepine -2-she and 2- (4- -me tylphenyl) -e tittbromid.
Output 23% of theoretical, so pl. 109-11GS.
%: C 69.04; And 8.07;
Calculated N 5.75.
C 68.84, H 7.90,
Calculated N 5.75.
Found,%; N 6.03.
and 2- (3methoxy-2H-3-bekazazepin-2-one 5-methoxyphenyl) ethyl ethyl.
The output of 25% of theoretical, so pl. 125-127 ° C.
C, 66.85; H 7.81;
0
C 65.68, H 7.67,
five
five
Calculated. %: Bh 5.57,
Found N, 5.20.
PRI me R 40. Throchloride 3-. t2 (3, 4,5-trimegoxif}} iseth-ethyl-py-- per1adin-2-yl-etx1-2 / -7,8-dimethox 1- -15 ZU 4, 5 - tetrag-dro-2H-3 -Benzazepin-2-eye receive; similar to Example 1 of 3- (piperidin-2-yl) -eth-I-2} - -75 8-diketox-2H-3-benzazepin-2-one and 2- (3,4 W-trimethoxyphenyl-ethyl-Sfomnda .
Turn 15% of the theoretical, so pl. 138-140 ° C.
Calculated,%: C 63.98; H 7.70; N 4.97.
Found,%: C 63.74; H 7.55; N 4.65.
EXAMPLE 41 (2-Fluorophenyl) -e-tyl-piperidine-1-3-yl} -methyl / -7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2 hydrochloride -She and
 . -t (2-fluorophenyl) ethyl bromide.
Output 49% of theoretical, so pl.
210 C.
55
Calculated,%: C 60.82; H 6.87; C, 60.88; H 6.73;
5.46,
Found% 5.60:
Rg value
g 0.33 (ci-shica gel, methylene chloride - methanol 10: 1).
L p and m: p 42. Hydrochloride 3 - // iN- (4 (rtorfenip} -ethyl / -hosheridin-3-yl | -methyl 7, odimethoxy-1,3 "4,5-tetravdro-2H- 3-6enzazepin-2-it is obtained by-analogously to example 1 from
3- (piperidin-3-yl) -methylZ-7,8-dimwt hydroxy-1,3,4,5-tetrahydro-2H-3-bH9ase ping-2-one and 2- (4-ftarphenyu1) -ethylbro mkda
Output 56 from the theoretical, mp 245 C (decomp.).
Calculated,%: C 65.47; H 7, I8j N 5.87.
Found,%: C 65.78j H 7.25; J 5.99.
A value of 0.31 (sipicagel, methylene chloride - methanol 10: 1),
Example 43, 3- / f N-G2- (4-aminofe nnl) -e thyl J-piperidin-3-yl} -methyl / -7,8-dimethoxy-1, 3, dihydrochloride -tetrahydro-2H-3-benzasepln-2 (v / iS
1.7 g (0.0036 mol) of 3- / CN-C2- (4-.-Nitrophenyl) ethyl-piperidium-3-yl | - -methyl / -7,8-dimethoxy-1,3,4, 5-tetrahydro-2H-3-benzazepine-2-one in 40 ml of methanol is hydrogenated in the presence of 0.3 g of 10% palladium on carbon for 2 hours at room temperature and a pressure of 5 bar of hydrogen. The catalyst is then sucked off and the methanol is distilled off in vacuo. From a solution of the residue obtained in acetone
By adding methanol hydrochloric acid
Lots precipitated hydrochloride
Output 1.1 g (59.8% of theoretical), so pl. 236-240 C.
Calculated,%: C, 61.17; H, 7.31; N 8; 23.
Found,%: C 60.85; H 7.63; N 8.12.
PRI and eper 44. 3- / Cm-2- (3-Label si-4-hydroxyphenyl) -typ-piperidine- -3 Cl} -methyl / -7,8-dimethoxy-1,3,4, 5- - Te trahydro-2H-3-benzazepin-2-one.
 2- (4-Benzyloxy-3-methoxy-phenyl) -ethylJ-piperidin-3-yl} -methyl / - -7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine 2-one is prepared analogously to example 1 from 3-C (piperidin-) -methylJ-7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one and 2- (4- benzyloxy-3-methoxyphenyl) ethyl bromide.
. 56% of theoretical, mp,
Calculated,%: C 68.61; H 7.28; N 4.71.








Found: C 68.80 / H 7.38 N 4.73.
3 - / {N-G2- (3-Methoxy-4-gvdroxyphenyl) -ethyl} -piperidin-3-yl-methyl / -. -7,8-dimethoxy-f, 3,4,5-tetrahydro-2H-3-benzazepi -2-one is prepared as in Example 43 of 3 - / (N-C2- (4- -benzyloxy-3-methoxyphenyl) -ethyl} -piperidin-3-Sh1} -metyp-7,8-dimethoxy--1,3,4,5-tetrahydro-2H-3-benzazepin-2-one in glacial acetic acid.
Output 7715 from the theoretical, so pl. 173-175 C.
Calculated Z: C 69.21 J H 7.74; N 5.98.
,%: C 69.07} H, 7.79; N, 6.06.
Analogously to Examples 1-44, the following compounds were prepared.
45. Hydrobromide 3 - / {k- 2- (3,4-di-methoxyfennp) -ethyl 7-pshtercherin-3-yl3 - -methyl / -7,8-dime toxi-G, 3,4,5-te - gvdro-2H-3-benzazepin-Mr., so pl. 225-227 ° C.
Calculated,%: C 59.68; H 6.98} and 4.97.
Found,%: C 59.45, H 7.10) N 5.00.
46. (3,4-Dimethoxyphenyl) -ethyl-j-pipervdin-3-yl-j-methyl-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one hydrochloride, t. square 117-121 C.
Calculated,%: -C 65.04 H 67.21
N 5.42.
Found,%: C 64.86; H 7.18- N 5.35.
47. DihydrochlorochC 3- / fN- 2- (3,4-dimethoxyfinyl) -ethylJ-piperidin-3-yl metil / -7,8-dimethoxy-2,3,4,5-tetrahydro-1H-3 - benzazepine, so pl. 238-240 0.
Calculated,%: C, 62.08; H 7.91, N 5.17.
Found Z: C 61.88i H 7.84 / N5.42.
48. 3- / m-E2- (3,4-di-methoxyphenyl) -ethyl} -piperidin-3-yl--me TIL / -7,8-dime to-1,3,4,5-tetra hydrochloride - hydro-2H-3-benzazepin-2-thione, so pl. 206-207 C.
Calculated,%: C, 62.84; H 7.35; N 5.24; S 5.99.
Found,%: C 62.54; H 7.43, N 5.35; S 6.15.
49.3- / c-C2- (3,4-Dimethoxyphenyl) - -ethyl pipervdin-3-yl} -met1sh / -7,8-dime to-1,3, 4, 5-those trahydro- / H-3- benzazepine, 2-dione, so pl. 130-132 C.
15 1А4207316
Calculated,%: C, 67.72; H, 7.31; Found,%: C, 70.5 &7.80;
N 5.64, .N 5.27.
Found,%: C 67.53; H 7.14; 56. 3- / (3,4-Dimethoxiphenyl) - N 5.65. J-α-ethyl-hexahydroazepin-2-yl} -ethyl-50. Hydrochloride (3,4-di - 2 / -7.8 dimethoxy-1,3,5,6-tetragide-metoksifenil) -ethyl-piperidine- 3-yl) -ro-2H-3-benzazepn-2-one.
- meths1 / -7,8-dimethoxy-1-hydroxy-1,3. Calculated,%: C 70.56; H, 8.29;
4,5-tetrahydro-2H-3-benzazepin-2-one, 5.49.
m.p. 118-124 S. p. 10 Found: C 70.60 H 8.34;
Calculated,%: C, 62.85; H 7.35; 5.37.
N 5.24. IR (methylene chloride); 1650 cm (CO).
Found,%: C 62.60; H 7, (3,4-Limetho-1. Siphenl) N 5.30. -Ethyl-pyropoly, zinc-3-ketyl / -7.8- 51. Dihydrochloride (4-ami-15 Dimethoxy-1, 3-dihydro -2H-3-benzenophenyl) ethyl-piperidin-3-yl-me-pin-7 on.
thyl / -7,8-dimethoxy-1,3,4,5-tetrahydyl IR (methten chloride): 1655 cm (CO).
ro-2H-3-benzaeepin-2-it, so pl. 236-Vych. -: -: but,%: C 69. SH; P 7.35;
240 ° C. N 6, 00
Calculated,%: C, 61.17; H 7.31, .20 Found,%: C 64.3 /; : .,/eight;
M 8.23. N 6.12.
Found,%: C 60.85; H 7.63-58, (3,4-Dimethoxyphenyl) K 8.12. Liquid-pyrrolide-3-yl} -methyl / -7.852. Hydrochloride 3 - / ((4-acetic - dimethoxy-1,3,4,5 tetrag1-de-2H-3-aminophenyl) et-1-piperidin-3-yl } -me-25-benzazepin-2-one.
thyl / -7,8-dimethoxy-1,3,4,5-tetrahydro-Vitisleco,%: C, 69.29; H, 7.75;
ro-2I-3-5enzazepin 2 it, so pl. 187-5,98.
192V. Found,%: C 69.20 H 7.84;
.K 5.92.
Calculated,%: C 65,16t H 7,42; 30 59, 2- (3-label hydrochloride 8,14, si-; - mat;; sulfoxyloxyf 1IL) -ethyl Found,%; C, 64.95; H 7.45; -lilies.) Di-3-1sh Lms tnl / -7,8-dimetok N 7,94. 5 3 "4 5 - thstrag1vdro-2H-3-benzaz53. (3,4-Дн1 5-methoxyphenyl) - pi; -2-o and; tltl. 202-204 ° C. -ethyl-p1 sheridin-3-Sh1) -methyl / -7,8-di-35 15pigiplot. %: C 57.67; H 6.74; methox-2,3-dig ldro-1H-benzazepine. ;,P; and 5 ,, 50,
The value of R 0.5 (alumina,.: Ndeco%; C 57.62J H 6.91;
the solvent is 2% ethanol in methnlen- 4.84 S 6. 31.
Chloride). Biol-cheskny test.
Calculated,%: C 72.07; H,.; O Effect on the frequency of cardiac n. 6.00 ,. ;; :: G-1JY AT KRYS.
Found%: C 71.90-, H 8.3: -, iu2 rats with average weight 250k 5 89. investigated the effect of the compounds
54.Hydrochloride (3,4 di forms of (I) for the frequency of cardiac coke methoxyphenyl) -atsh1-piperidin-3-CJ -,; For this reason, rat narcotizidiro-methyl / -7,8-methylenedioxy-1,3-dig d-zyli pentobarbital (50 mg / kg, internally 2H-3-benzazepin-α-one, so pl. 199-triperitoneally and 20 mg / kg subcutaneously). Is-201 ° C. The investigated compounds were injected
Vrshgleno,%: C 64.73; H 5.64 IV in the form of an aqueous solution in the belt
M 5-. 59. rQ vein (0.1 ml / 100 g). Dose studied
Found,%: C, 64.77 H, 5.55 ;, the compounds were 5 mg / kg.
W, 7. Blood pressure was measured with
bj. (3,4-Dimethox; i-ennl) by the power of a cannula inserted into the belt ar-ethyl 3-hexahydroacene-2-yl-ethyl-terry, and the heart rate of -2 / -7, 8-dimethoxy-1,3 dihydro- 2H-3 - days were recorded using elec-benzozepin-2-one, oil. - trocardiograms F. heart rate
IR (matylenchloride; cm (CO). Cuts in animals for the control
Calculated,%: C / 70.83-, K 7.93; the period was 350 and 400 beats
N .in a minute.
17
The table shows the results of experiments with chemicals and known compounds.
Compounds (I) belong to the category of phlotoxic substances.

权利要求:
Claims (1)
[1]
Invention Formula
The method of obtaining cyclic amine derivatives of the general formula
E-CH
/ (Sn,) w
NG
(CH2) p
X
de
whether
at
in 20
25
groups-CHj-CFI, j-,,
-sn, -so
X
methylene or thiocarboiyl OH
groups -CO-CO-bn-eo-i
i
methylene, with the atoms X equipped with the letter X being bound to phenyl core K C – C –Al xyen; G - C, -C-alksh1en, and one
the methylene group bound by the ZO to the phenyl core can be replaced by an oxygen atom, each Cf – Cj alkoxy group
or together form a methylenedioxy group; five
R. - hydrogen, halogen,.-alkyl or C 1 -e C-alkoxy group, hydroxyl, itro- or trifluoromethyl .. group}
hydrogen, C -Cj-alkoxy, o-amino, methanesulfonyloxy or acetylamino group, or R and R together form a methylenedioxy group 4 hydrogen, halogen or alkoxy) 1-5,
0-2, and the type must include the numbers 3, 4 or 5, whether their gi, p. Gala, lt, OTLI ch and w, and with that, the connection is
m p
45
50
t442073 8
subjected to interaction with the compound of the General formula
Hal-С
where G, Cd and Rf have the indicated values
R K. with the exception of a hydroxyl group which can be protected by a benzipnyl group, Hal is a halide,
followed, if necessary, by the removal of the nucleotide group and the introduction of the target product in free form or in the form of hydrohalides.
X
(CIS)
W
H
E-Cp we
(cis
B,:,
. This is the indicated value.
. Hydrochloride 1- (6,7-dimstoksn-3 4-dihydro-2K-nzo HIKolin 1-one 2-1Ш J-3-N-MeTHH-K-2 (3,4-dimethoxy-NSh1) -ethyl - amino propane.

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法律状态:

优先权:

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申请号 | 申请日 | 专利标题

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---