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    • 专利摘要:
    Compounds of general formula I <IMAGE> (wherein A represents a <IMAGE> group, wherein R7 represents a C1-3 alkyl group, and B represents a methylene or carbonyl group or A represents a -CO-CO- group and B represents a methylene group; E represents an optionally substituted ethylene, n-propylene or n-butylene group; G represents an optionally substituted methylene or ethylene group; R1 and R2 represent a hydroxy, alkyl, alkoxy or phenyl-alkoxy group or one of them represents a hydrogen atom or together they represent an alkylenedioxy group; R3 and R4 represent hydrogen atoms, halogen atoms, trifluoromethyl, hydroxy, alkyl, alkoxy or cyano groups or one of them represents a nitro group or together they represent an alkylenedioxy group; R5 represents a hydrogen atom, an alkyl, hydroxy, alkoxy or optionally substituted amino group; and R6 represents a hydrogen atom, an alkyl, alkenyl, phenylalkyl or acyl group) and acid addition salts thereof show heart-rate reducing activity. <IMAGE>
    公开号:SU1160935A3
    申请号:SU823435639
    申请日:1982-05-13
    公开日:1985-06-07
    发明作者:Рейффен Манфред；Гейдер Йоахим；Гауэль Норберт；Аустель Фолькгард；Эберлейн Вольфганг；Ноль Клаус；Пипер Гельмут；Крюгер Герд；Кек Йоганнес；Кобингер Вальтер；Лиллие Кристиан
    申请人:Др.Карл Томэ Гмбх (Фирма)；
    IPC主号:
    专利说明:

    where G, Rg, R and Rg have the indicated values J V is a halogen atom or a group -NH, where R has the indicated value. “S. moreover, V is different from U, -c followed by the removal of the target product in a free form or in the form of a salt., 2. The POP.1 method, which differs from and in that the reaction is carried out in a solvent medium .116 3. The method according to PP.1 and 2, characterized in that the reaction is carried out in the presence of a base. 4. The method according to claims 1 to 3, about tl and in that the reaction is carried out at a temperature ranging from the boiling point of the solvent used to.
    The invention relates to the field of the production of new products, benzase pins of the general formula G A Hb 3. NENG where A is the group -CH-CHg-, -NH-CO-, or in which R 7 5 5 is an alkyl group with a number of carbon atoms Lerode 1 -3; B is a methylene or carbonyl group; j E is an ethylene, n-propylene group; G is an ethylene group; R and R. are the same or different, denote hydroxyl, alkyl, alkoxy or phenylalkoxy groups in which the alkyl part may contain 1–3 carbon atoms, or one of these radicals may also mean a hydrogen atom or both radicals can form an alkylenedioxy group with 1 or 2 carbon atoms Rj and R are the same or different, mean hydrogen or halogen, hydroxyl, alkyl or alkoxy groups respectively with 1-4 carbon atoms, trifluoromethyl, cyano or one of these radicals can also mean a nitro group or both together, they mean an alkylenedioxy group with 1 or 2 carbon atoms, Rg is a hydrogen atom, an alkoxy, amino, dialkylamino, alkoxycarbonylamino or trifluoroethylamino groups salts, in particular, their physiologically digestible acid addition salts, with inorganic acids, which possess pharmacological properties, namely, a blood pressure lowering action, in particular, a lowering heart rate. . The purpose of the invention is to develop, on the basis of a known method, a method of producing new compounds possessing valuable and improved pharmacological properties. Example 1. 1- (7, 8-dimethoxy 71,3-dihydro-2H-3-benzazepin-2-one-3-yl) -3- {c-methyl-H-C2- (3,4-dimethoxyphenyl) hydrochloride -ethyl-amino-propane. A. 1- (7,8-Dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane. 131, 5 g (0.6 mol) of 7,8-dimethoxy-1, 3-dihydro-2H-3-benzazepin-2-one are suspended in 900 ml of dimethyl sulfoxide and 80.8 g (0.72 mol of a) tertiary butyl potassium. After 10 minutes, the resulting solution), under ice cooling, is added to 77 ml (0.72 mol) of 1-bromo-3-chloropropane and 300 ml of dimethyl sulfoxide. After 1 h, pour into ice water. After a short time, the oily residue crystallizes. The precipitate is sucked off, dissolved in acetone, precipitated again with water, sucked off and dried. Yield 155.5 g (87.3% of theory), m.p. 101-103C.
    B. 1- (7,8-Dimethoxy-1, 3-dihydro-2H-3-benzazepin-2-one-3-yl) -3- {N-methyl-N- 2- (3,4-dimethoxyphenyl) hydrochloride ) -ethyl-amino-propane.
    5.9 g (0.02 mol) of 1- (7,8-dimethok-5 Si-1,3-dihydro-2H-3-benzazepin-2-one-3-Sh1) -3-chloropropane and 11.7 g (0.06 mol) of K-methyl-2- (3,4-dimethoxyphenyl) -ethylamine is heated for 3 hours to cool, and dissolved 10 in ethyl acetate / water. The organic phase is separated, washed three times with 1% acetic acid and extracted twice with 2N. hydrochloric acid by shaking. The succinate extract is alkalinized and extracted with methylene chloride. The extract solvent is removed in vacuo, the residue is dissolved in acetone and the hydrochloride is precipitated with ethereal hydrochloric acid. 20
    Output 6, (70.3% of theory), t, pl. 191-19GS (decomp.)
    Example 2. 1- (7,8-dimet (eksi-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-N-methyl-S) dihydrochloride - 2- (3,4-dimethoxy-phenyl) -eth-13-amino-propane.
    A.1- (7,8-Dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-hl ortr o pan., "
    Prepared analogously to example 1 by the exchange reaction of 7,8-dimethoxy-1.3,
    4,5-tetrahydro-2H-3-benzazepin-2-one with 1-bromo-3-chloropropane (yield 50% of theory) or analogously to example 4 by catalytic hydrogenation of 1- (7,8-dimethoxy-1,3- dihydro-2H-3-benzazepin-2-On-3-yl) 3-chloropropane.
    Output 88% of theory, so pl. 8483C ..
    B. 1- (7,8-dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-m-methyl-Y-2- (3, 4-dimethoxy-phenyl) -e, thyl-amino of J-propane.
    Prepared analogously to example 1B by the reaction of exchange 1- (7,8-dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane with N-methyl-2 - (3,4-dimethoxy-phenyl) -ethylamino-50 n.
    The output of 75.2% of theory, so pl. 135357 ° C (decomp). .
    Example 3. 1- (7,8-dimethoxy-1,3-dihydro-2H-3- 55-benzazepin-2-one-3-yl) -3-N-methyl-N-C2- (4-methoxyphenyl) hydrochloride ) -ethyl-amino-propane.
    Prepared analogously to example 1B by the reaction of exchange of 1- (7,8-dimethoxy-1, 3-dihydro-2 {| -3-benzazepin-2-one-3-yl) -3-chloropropane with K-methyl-2- ( 4-methoxy-phenyl) -ethylamine.
    Output 76.2% of theory, so pl. 139142С.
    Example 4. 1- (7, 8-methylenedioxy-1,3-dihydro-2H-3-benzazepin-2-one-3-yl) hydrochloride-3- {N-methyl-N- 2- (3,4- dimethoxyphenyl) ethyl-amino-propane.
    A. 1- (7,8-Mothylenedioxy-1,3-dihydro-2H-benzazepin-2-on-3-yl) -3-chloropropane.
    . It is obtained analogously to example 1A by the exchange reaction of 7,8-mets-1-dioxy-1, 3-dihydro-2H-3-benzazepin-2-one (mp. (Dec) with 1-bromo-3-chloropropane.
    Output 72.1% of theory, so pl. 7579C.
     B. Hydrochloride 1- (7,8-methylenedioxy-1, 3-dihydro-2H-benzazepin-2-one-3-yl) -3- {M-methyl-M- 2- (3,4-dimethoxyphenyl) -ethyl 3-amino propane.
    Prepared analogously to example 1B by the reaction of exchange of 1- (7,8-methylene. Dioxy-1,3-dihydro-2H-benzazepin-2-one-3-yl) -3-chloropropane with N-methyl-2- (3, 4-dimethoxyphenyl) -ethylamine.
    Output 77.2% of theory, so pl. 185187 ° C.
    Example 5. 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-6eH3a3enHH-2-oH-3-mi) dihydrochloride, 2- (N-methyl-N- 2- ( 3,4-dimethoxyphenyl) Chatel-amino T) -propane.
    22 g (0.075 mol) (7,8-dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) propyl-methylamine with 7.2 g (0.036 mol) 2- (3,4-dimethoxyphenyl) ethyl chloride is heated for 20 hours to 140 ° C. After the reaction product is dissolved in methylene chloride, the solution is washed once with 2N. sodium hydroxide solution and twice with water, dried over sodium sulfate and concentrated. The residue is purified by chromatography on a column of silica gel (grain size 0.063-0.2 mm; eluate methylene chloride / methanol 10: 1). The product thus obtained is dissolved in acetone and hydrochloride is precipitated with ethereal hydrochloric acid.
    Output 8.0 g (45% of theory), t. mp 135-136 ° C (decomp).  Example 6  1- (8-methoxy-1,3,4,5-tetrahydro-2H-3- dihydrochloride dihydrochloride.  -benzazepii-2-one-3-yl) -3- {N-metip-Y-C2- (3,4-dimethoxyphenyl) -ethyl-amino-propane.  BUT.  1- (8-Methoxy-1,3-dihydro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane.  Prepared analogously to example 1A by the reaction of exchange of 8-methoxy-1,3-dihydro-2H-3-benzazepin-2-one (t. square  189-190 ° C) with 1-bromo-3-chloropropane.  . Yield 23% of theory, IR spectrum (methylene chloride): 1655 (CO).  B.  1- (8-Methoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloro propane Obtained by catalytic hydrogenation of 1- (8-methoxy-1,3 -dihydro-2H-3-benzaz. epin-2-one-3-yl) -3-chloro propane.  Yield 67% of theory, IR spectrum (methylene chloride): 1645 cm (CO).  B.  1- (8-methoxy-1,3, 4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- {K-methyl-L- 2- (3,4-dimethoxyphenyl) dihydrochloride -ethyl-amino 1 | -propane.  Prepared analogously to example 2B by the reaction of exchange 1- (8-methoxy-1, 3,4,5-tetrahydro-2H-3-ba. nzazepin-2-one-3-yl) -3-chloropropane with H-methyl-2 (3,4-dimethoxyphenyl) -yylamine.  Output 14% of theory, t. square  118121 C. ; Example 7  1- (7,8-Dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-H-metsh-1-Y-2- (4-amino-3 -chlorophenyl) -ethyl-amino-propane.  Prepared analogously to Example 5 from N-3- (7,8-dimethoxy-1,3,4,5-tetrahydride.  ro-2H-3-benzazepin-2-one-3-yl) -propyl-meth- chlorine and 2- (4-amino-3-chlorophenyl) -ethyl bromide.  Butter.  IR spectrum (methylene chloride), cm-j 3380, 3480 (Shg); 1645 (CO), UV spectrum (ethanol), nm: L 238 (0.16) -, 280-290 (0.05).  PRI me 8.  1- (7,8-Dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-Sh1) -3- (n-ethyl-K-2- (4-amino- 3, 5-dichlorophenyl) ethyl. amino j-nopan.  Prepared analogously to Example 5 from (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3 yl) propyl-ethylamine and 2- (4-amino-3, 5 . - dichlorophenyl) ethyl chloride.  Butter.  IR spectrum (methylene chloride), cm-: 3390, 3480 (NHj); 1650 (CO).  356.  UV-spectrum (ethanol), nm: 240 (0.13) -, 280-290 (0.05) -.  Example 9  1-C7,8-Dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl-3- {N-2- (4-amino-3, 5-dichlorophenyl -ethyl-amino-propane.  Prepared analogously to Example 5 from H-C3- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) propyl-methylamine and 2- (4- amino-3, 5-dichlorophene1) ethyl chloride.  T. square  94104С.  Etc.  and measure 10.  , 8-Dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl-3- {N-methyl-H- 2- (4-amino-3, 5-dibromophenyl ) -Atsh1 -amino-propane.  Prepared analogously to Example 5 from N- 3- (7.8-: dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -propyl-3-methylamine and 2- ( 4 amino-3, 5-dibromophenyl) ethyl chloride.  T. square  108-112С.  Example 11  , 8-dimethoxy-1, 3-dihydro-2H-3-benzazepin-2-one-3-yl-3- {N-methyl-I-2- (4-amino-3, 5-dichlorophenyl) - ethyl ) -amino-propane.  Prepared analogously to example 1B from 1- (7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane and 2- (4-amino-3, 5- dichlorophenyl) -N-methylethylamine.  Butter.  IR spectrum (methylene chloride), cm -: 3390, 3480 (NH); 1655 (CO).  UV spectrum (ethanol), nm: 238 (shoulder, 0.25) -, 280 (0.1); 303 (0.12).  PRI me 12.  1-C7,8-Dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl-3- {H-ethyl-H-2- (4-amino-3, 5-dibromophenyl) -ethyl-amino-propane.  Prepared analogously to example 2B from 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-basezazepin-2-one-3-yl) 3-chloropropane and 2- (4-amino-3 , 5-dibromfensh1) -N-ethylethylamine.  Butter.  IR spectrum (porous methylene), cm: 3380, 3480 (W); 1645 (CO).  UV spectrum (ethanol), nm: 240 (shoulder, 0.13); 280-290 (0.04).  Example 13  , 8-Dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazin-2-one-3-yl-3-y-methyl-Y-2- (4 amino-3, 5-dichlorophenyl) ethyl -amino-propane.  Prepared analogously to example 2B from 1- (7,8-dimethoxy-1,3,4,5-tetra7, hydro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane and 2- (4- amino-3,5-dichloro-phenyl) -N-methyletha-amine.  T. square  94104 S.  Example 14  1-7.8-Dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazPIN-2-OH-3-IL-3- {H-isopropyl-H-2t (4-amino-3, 5 -dichlorophenyl) -ethylZ-amino-J-propan.  Prepared analogously to Example 2B from, 8-dimethoxy-1,3,4,5-tetrahyd ro-2H-3-benzazepin-2-one-3-yl) -3-chloro.  propane and 2- (4-amino-3, 5-dichloro-phenyl) -N-isopropylethylamine.  T. square  hydrochloride less (sintering starts on with.  (IR spectrum (methylene chloride),: 3390, 3480 (1650 (CO).  UV-spectrum (ethanol), nm: 238 (0.13) -, 280-290 (0.05).  PRI m e: p 15.  1-C7 hydrochloride 8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-Sh1 -3- {m-methyl-H-1-methyl-2 - (4- amino-3, 5-dichlorophenyl-ethyl-amino-propane.  Prepared analogously to example 2B from 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane and 2- (4-amino- H, 5-dichloro-phenyl) -1-methyl-N-methyl-ethyl amine.  T. square  118-128 0 (decomp.)  Example 16  Hydrochloride 1.  - (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) (4-amino-3,5-dichlorophenyl) ethyl J-amino propane .  Prepared analogously to example 2B from 1- (7,8-dime toxi-1,3,4,5-ter tr ago po 2H-3-benzazepin-2-one-3-sh1) -3-chloro propane and 2- ( 4-amino-3, 5-dichlorofensh1) -ethylamine.  T. square  236-241 ° C.  Example 17  1- (7,8-Dimethoxy -1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- {N-methyl-H- 2- (4-ami- but-3-chloro-5-metsh1phenyl) -atsh1 -amino | -propane.  Prepared analogously to example 2B from 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-Sh1) -3-chloropropane and 2- (4-amino- 3-chloro-5-methylphenyl) -K-methyl &amp; tylamine.  T. square  60 ° С (sintering, melting at 73 ° С).  IR spectrum (chloride metsten), cm-: 3390, 3480 (1650 (CO).  UV spectrum (ethanol).  D Myx nm: 237 (0.14); 280-290 (0.05).  Example 18  1- (7,8, -dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine-2-on-3-yl) -3-N-Me5 hydrochloride-3-N-Me5 in yl-L- 2- (3 5-dichloro-4-oxyfennl) ethyl -aminoj-propane.  Prepared analogously to Example 2B C 1- (7,8-dimethoxy-1,3,4,5-tetraido-2H-3-benzazepin-2-one-3-Sh1) -3-chloropane and 2- (3.5 -dichloro-4-hydroxyphenyl) N-methylethylamine.  T. square  225C.  Example 19  1- (7,8-Dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazPIN-2-OH-3-IL) -3-N-methyl-Y-2- (3-chloro-5 -fluoro-4- / 3, / e, D-trifluoroethylaminophenyl) -ethyl-amino-propane.  Prepared analogously to example 2B from 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepine-2-on-3-yl) -3-chloropropane and 2- (3-chloro 5-fluoro-4-ue, I, p-trifluoroethylaminophenyl) -K-methylethylamine.  m / e 545/547 (C2 Hz1C1P4KzOz; 546.03).  Example 20  1- (7,8-Dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-N-methyl-L-2- (4-amino- 3-chloro-5-fluorophenyl) -tcr J-amino-propane.  Prepared analogously to example 2B g13 1- (7,8-dimethoxy-1,3,4,5-tetra-.  hydro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane and 2- (4-amino-3-chloro-5-fluorophenyl) -M-methylethylamine.  m / e 463/36 5 (, S1RKZO 463.99).  Example 21  1- (7,8-Dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-Sh1) -3- {M-methyl-Y-2- (4-amino- 3-chloro-5-trifluoromethylphensh1) ethyl-amino-propane.  Prepared analogously to example 2B from 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloroprop-ana and 2- (4- amino-3-chloro-5-trifluoromethylphenyl) -H-metsh1ethylamine.  Butter.  IR spectrum (. methylene chloride), m-: 3410, 3510 (1650 (CO) 610, 1520 () -, 2800 (N-alkyl); 830 (OCH3).  UV spectrum (ethanol), LL (O1K. with nm: 41 (0.33), 285 (0.10), 310 (0.08).  Example 22  1- (7,8-Dimethoki-1, 3,4,5-tetrahydro-2, 1-3-benzazin-2-one-3-yl) -3- {M-metsh-1-Y- 2- (4-amino-3 -cyan-5-fluorophenyl) ethyl} amino} -propane.  Prepared analogously to example 2B of 1- (7,8-dimethoxy-1,3,4,5-tetraido-2H-3-benzazepin-2-on-3-yl) -3 chloropropane and H-methyl-2- (4- aminoZ-cyan-5-fluorophenyl) ethyl} -amine.  IR spectrum (. methylene chloride), 3400, 3490 (NHg); 2830 (OCH,), 2220 (CN); 1650 (CO).  Example 23  1- (7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one-3-yl) -3- {N-benzyl-H-C2- (3. Hydrochloride hydrochloride). 4-dimethoxyphenyl, -Epsh1 -amino-propane.  Prepared analogously to example 1B and 1- (7,8-dimethoxy-1,3-dihydro-2H-ben zazepin-2-one-3-yl) -3-chloropropane and 2- (3,4-dimethoxyphenyl) -N- benzylethyl amine.  Yield 51% of theory, t. square  102c (dec.)  I P p. and measure 24.  1- (7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one-3-yl) -3- {n-methyl-N-C2- (3, 4-netilenedioxyphenyl) hydrochloride -ethyl-amino | -propane.  Prepared analogously to example 1B from 1- (7,8-dimet. hydroxy-1,3-dihydro-2H-3-benzazepin-2-one-3 yl) -3-chloropropane and 2- (3,4-methylenedioxyphenyl-N-methylethylamine.  The output of 48% of theory, t. square  160 Example 25.  1- (7,8-dimethoxy-1,3-dihydro-2H-3-beta-zazepin-2-one-3-yl) -3- (M-benzylmethyl amino) propane hydrochloride.  Prepared analogously to example 1B from 1- (7,8-dimethoxy-1,3-dihydrr-2H-benzazepin-2-one-3-yl) -3-chloropropane and N-methyl-benzylamine.  Output 92% of theory, t. square  208.  209C.  Example 26  Hydrochloride 1- (7, B-dimethoxy-1,3-dihydro-2H-3-beta zazepin 2-one-3-yl) -4- {N-methyl-Y-2- (3,4-dimethoxyfensch1) - etsh1 -amino-butane.   Prepared analogously to example 1B from 1- (7,8-dimethoxy-1,3-dihydro-2H-3-benzazepii-2-one-3-yl) -4-chlorobutane and N-methyl-2 (3,4 dimethoxyphenyl) - ethylamine. .  Output 85% of theory, t. square  162164С.  Example 27  1- (8-PROPOXI-1,3-dihydro-2H-3-benzazepin-2-on 3-ShI) hydrochloride-2- {N-m-I-N-C2- (3, 4-dimethoxyphenyl) -ethyl-amino ethane  Prepared analogously to example 1B from 1- (8-propoxy-1 3-dihydro-2H-3-benzo zepin-2-one-3-Sh1) -2-chloroethane and N-methyl-2- (3,4-dimethoxyphenyl) - ethylamine.  510 Yield 31% of theory, t. square  155isy c.  .   .  Example 28  Isomeric mixture of 1- (7,8-dimethoxy-1,3-DIGIDRO-2H-3-benzazepin-2-one-3-yl) -3- {N-metsh1-N-2 (4- and 2-nitrophenyl) -ethyl-amiHoZ-propane.  Prepared analogously to example 1B from 1 - (7,8-dime toxi-1,. 3-dihydro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane and N-methyl-2- (4- and 2-nitrophenyl). - ethylamine.  Yield 70% O. T theory.  IR spectrum (methylene chloride), 1655 (CO) i 1510 and 1345 (Shg).  NMR spectrum (CDClI / DjO) cL, h / million , 8.10 (C1 (Hz), 2H (arom. ), 4-nitro compound), 7.83 (o1 (Hz), 2H (arom. ), (2-nitro compound).  Example 29  1- (7,8-dimethoxy-5-methyl-T, 3-dihydro-2H-3, 4-benzodiazepin-2-one-3-Sh1) dihydrochloride -3- {N-methyl-H- 2- (3 , 4-dimeloxyphenyl) ethyl-amino-propane. .  .  Prepared analogously to example 1B by the reaction of exchange of 1- (7,8-dimethoxy-5-methyl-1, 3-dihydro-2H-3,4-benzodiazepin-2-one-3-yl) -3-chloropropane with M-methyl -2- (3,4-dimethoxyphenyl) ethylamine.    Transmission 24.2% of theory,. t. square  106 ° C.  Example 30  1- (7,8-Dimethoxy-1, 3-dihydro-2H - 3-benzazepin-2-one-3-shI) -2-oxy-3 {N-methyl-N- 2- (3,4- dimethoxyphenyl) -o-1-amino-propane.  BUT.  1- (7,8-Dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one-3-yl) -2,3-epoxypropane.  Prepared analogously to example 1A.  by exchange reaction of 7,8-dimethoxy-1, 3-dihydro-2H-3-benzazepin-2-one with epichlopidrin.  Output 94.5% of theory.  IR spectrum (methylene chloride), cm-: 2830, (COHj) -, 1660 (CO).  B.  1- (7,8-Dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one-3-yl) -2-oxig-3-N-methyl-N 2- (3,4-dimethoxyphenyl) -ethyl amino Vnpo pan.  8.25 g (0.03 mol) of 1- (7,8-Dimethoxy-1, 3-dihydro-2H-3-benzazvpin-2-one-3-yl) -2,3-epoxypropane is dissolved in 100 ml methanol and mixed with 5.85 g (0.03 mol) of N-methyl-2- (3,4-dimethoxyphenyl) ethylamine and boiled for 3 hours with a reflux condenser.  The methanol is distilled off in vacuo and the residue is purified on a column of silica gel with methylene chloride + 1% ethanol.  The output of 7.8 g (55.2% of theory).  IR spectrum (methylene chloride), 3600 (OH), 1650 (CO).  .  .  Found,%: C 66.16, H 7.26, N 5.80.  C2. , 2 (70.6).  Calculated,%: C, 66.36; H, 7.28; N, 5.95.  Example 31  1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-ben-zazepin-2-one-3-yl-3- {N-methyl-N- 2- (4 -nitrophenyl) -ethyl-amino-propane.  Prepared analogously to example 2B by the reaction of exchange of 1- (7,8-dimetok si-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane with N-methyl -2- (4-nitrofensh1) -ethylamine.  Output 56.5% of theory.  T. square  .  Example 32  1 - (7, 8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-Sh1) dihydrochloride-3- {N-methyl-H- 2- (3-nitro -4-acetylaminophenyl) ethyl-amine J-propane.  0.3 g (1.18 mmol) (7,8-dimethoxy-1, 3,4,5-tetrahydro-2H-3. -benzazepin-2-one-3-yl) -propyl-methylamine and 0.34 g (1.3 mmol). - (3-nitro-4-acetylaminophenyl) ethyl: bromide in 5 ml of chlorobenzene and 0.1 mp of pyridine are refluxed for 1 h.  The reaction mixture is cooled and the pyridine hydrobromide is filtered off with suction.  The filtrate is evaporated in vacuo and the residue is purified over alumina (neutral to activity II) with methylene chloride and 0.5% -HBiM ethanol as solvent.  The oil thus obtained is dissolved in acetone and dihydrochl is precipitated with ethereal hydrochloric acid. Yield 230 mg (57.7% of theory), T. square  170C.  Example 33  1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) tyl-K-2- (4-fluorophenyl) ethyl-amino - amino dihydrochloride propane.  Prepared analogously to the example of BZ p in that exchange reaction of 1- (7,8-dimethoxy -1,3,4,5-tetrahydro-2H-3-benzazepin -2-one-3-sh1) -3-chloropropane with N-methyl - 2t (4-F1: orphenyl) -ethylamine.  3512.  .  Output 68.7%, from theory, t. square  203C.  For example 34.  Dihydrochloride 1- (7,8-dimethoxy-. 1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-Sh1T-3- {N-methyl-N-C2- (2, b-dichlorophenyl) ethyl-amino-propane.  Prepared analogously to example 2B by exchange reaction of 1- (7,8-dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-np) -3 chloropropane with N-methyl-2- (2,6-dichlorophenyl) -ethnpamine.  Output 70.5% of theory, t. square  .  Example 35  1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-sh1) dihydrochloride 2- {N-Methyl-NC 2- (3,4- dichlorophenyl) -ethyl-amino-propane.  Prepared analogously to example 2B by the reaction of exchange of 1- (7,8-dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane with N-methyl-2 - (3,4-dichlorophenyl) -ethylamine.  Output 57.6% of theory, t. square  16GS.  Example 36  1- (7,8-Dimethoxy-1, 3-dihydro-2H-3-ba. chazazepin-2-one-3-yl) -2- {s-methyl-L-2- (3,4-dimethoxyphenyl) -ethyl-amino-istan.  BUT.  1- (7,8-Dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one-3-yl) -2-chloroethane.  Prepared analogously to example 1A by the reaction of the exchange of 7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one with 1-chloro-2-bromoethane.  Output 20% of theory, t. square  .  B.  1- (7,8-Dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one-3-yl) -2- {K-methyl-K-C2- (3,4-dimethoxyphenyl) -ethyl -amino j-ethane.  Prepared analogously to example 1B by the reaction of exchange of 1- (7,8-dimethoxy-1, 3-dihydro-2H-3-benzazepin-2-one-3-yl) -2-chloroethane with N-metsh-2- (3, 4-dimethoxyphenyl) ethylamine.  Example 37  Hydrochloride 1 (7, 8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2, 4-dione-3-yl) -3- {K-methyl-N- 2- (3, 4-dimethoxyphenyl) ethyl-amino-propane.  BUT.  1- (7,8-Dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2, 4-dione-3-yl) -3-chloropropane.  Prepared analogously to example 1A by the exchange reaction of 7,8-dimethyloxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2, 4-dione (t. square  235 ° C (dec)) with 1-bromo-3-chloropropane.  Yield 26% of theory, IR spectrum (KBG): 1660 cm- (CO), B.  1- (7,8-dimethoxy-1, 3,4,5-tetrahydro-2H-3 benzazepin-2, 4-dioi-3-yl) -3- {K-methyl-M- 2- (3, .  4-dimethoxyfe Chl) -ethyl-amino-1-pro is obtained analogously to the example of BZ by the exchange reaction of 1- (7,8-dimetok si-1,3,4,5-tetrahydro-2H-3-benzazepin-2, 4-dione-3 -yl) -3-chloropropane with M-methyl 2- (3,4-dimethoxyphenyl) -ethyl amine ,.  Output 35% of the theory of t. square  163164 ° C.  Example 38  1- (7-Benzyloxy-8-hydroxy-1,3,4,5-tetrachloro-2H-3-ben zazepin-2-one-3-yl). -3-- N-methyl-L 12- (3,4-dimethoxyphenyl) -ethyl-amino-propane.  BUT.  1- (7.8 Dioxy-1,3,4,5-tetraG1-shcho-2H-3-benzazepin-2-one-3-yl) -3-chloropropane.  8.9 g (0.03 mol) of 1- (7,8-dimethoc-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane solution in 100 ml of methylene chloride and at -60 ° C are mixed with 2.1 mp tribromide boron.  The reaction temperature is slowly raised to 20 ° C and stirred at this temperature for another 10 h.  By adding 100 ml of water and stirring for 1 hour, the resinous precipitate is converted to a crystalline form.  The precipitate is filtered off with suction and washed with water and methylene chloride.  For purification, the crystallized mixture is mixed with acetone and sucked off.  Output 7.3 g (90.2% of theory), t. Pl, G / 7-178 ° C, B, 1- (7,8-Oxy-8-benzyloxy-1,3, 4,5-tetrahydro-2H-3-benzazepin-2-.  -one-3 yl) -3-chloropropane and 1- (7,8-benzyloxy-8-oxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3 - chloropropane.  19 g (0.07 mol) of 1- (7,8-dioxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3 yl) -3-chloropropane and 10.6 g of carbonate potassium in a 250 mp dimethyl sulfoxide is mixed with 19.5 g (0.154 mol) of benzyl chloride.  The mixture is stirred at room temperature for two days, injected into ice water, and extracted several times with ethyl acetate.  The organic extracts are washed three times with water, dried over magnesium sulphate and concentrated in vacuo.  Isomer separation is carried out on a column of silica gel with methylene chloride and 3% acetone as a solvent.  Yield of 7-hydroxy compounds 6 g (23.8% of theory), t. Pl, 163: -165 C.  Yield of 8-hydroxy compounds 4.5 g (17.9% of theory), t. pl, 185-186 ° C, B, 1- (7-benzyloxy-8-hydroxy-1,3,4,5 tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- {N-methyl -N-2- (3,4-dimethoxyphenyl) -ethyl-amino | - propane.  Prepared analogously to example BZ by the exchange reaction of 1- (7-benzyloxy-8-OXI-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -4-chloropropane with L-methyl -2- (3,4 dimethoxyphenyl) ethylamine.  Output 75.4% of theory, t. square  128-; .  Example 39  1- (7-Oxy-8-benzyloxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- {N-methyl-H-C2- (3, 4-dimethoxyphenyl) ethyl-amino J-propane.  Prepared analogously to example BZ by the reaction of the exchange of 1- (7-hydroxy-8-benzyloxy-1, 3,4,5-t; etrahydro-2H-3-benzazepin-2-one-2-sh1) -u3-chloropropane with N -MeTmi-2- (3,4-dimethoxyphenyl) -ethylamine Yield 47.2% of theory, t. pl, 157-158 ° C.  Example 40  1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- {s-methyl-K-C2- (3,4 -dimethylphenyl) -ethyl-amino-j-propane.  Prepared analogously to example BZ by the exchange reaction of 1- (7,8-dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloro-prrpan with N-methyl -2- (3,4-dimethylphenyl) ethylamino;  Output 54.3% of theory, t. n, l  170172 days  Example 41  1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) dihydrochloride-3- | N-methyl-N-2- (4-tert-butylphenyl) -ethylJ-amino-propane.  Prepared analogously to the example of BZ by the exchange reaction of 1- (7,8-dimethoxy-1, 3,4,5-tetrag1adro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane with M-methyl-2 - (4-tert-butylphenyl) -ethylamine.  Output 49.4% of theory, t. square  146149С, Example 42.  1- (7,8-Dimethox -1,3,4,5-ditetrahydro-2H-3-benzazepin-2-one-3-yl) -3- {N-methyl-Y-2- (4-butoxyphenyl) -ethyl-amino-propane.  Prepared analogously to example 2B p, the exchange reaction of 1- (7,8-dimethoxy -1,3,4,5-tetrahydro-2H-3-benzazepin -2-one 3-yl) -3-chloropropane with N-methyl - 2- (4-n-butoxyphenyl) -ethylamine.  Output 55.3% of theory, t. square 67 (.  Example 43  1- (7,8, -№ 1 labels SI-1,3,4,5-tetrahydro-2H-3-benzazep -2-one-3-yl-3-N-methyl-Y-2- (2.4 , 6-trimethoxyphenyl) -ethyl-amino-propane.  Prepared analogously to the example of BZ by the exchange reaction of 1- (7,8-dimetok si-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane with N-me Tyl-2- (2,4,6-trimethoxyphenyl) ethyl amine.  Output 57.8% of theory.  IR spectrum (methylene chloride),. cm-, 1650 (C0) j 1520 (aroma.  ) Found: C, 61.75; H, 7.52; N, 5.18; C1, 7.34.  C HjjNjOj- HC1 (523.2): Calculated,%: C 62.00, H 7.51, N 5.35, C1 6.77.  Example 44  Hydrochloride 1-- (7,8-dimethyl-1,3-dihydro-2H-3-benzazepin-2-on-3-yl) -3- {N-methyl-N- 2- (3,4-dimethoxyphenyl ) -ethyl-amino-propane.  BUT.  1- (7,8-Dimethyl-1,3-dihydro-2H-3-beisazepin-2-one-3-yl) -3-chloropropane.  Prepared analogously to example 1B by the exchange reaction of 7,8-dimethyl-1, 3-dihydro-2H-3-benzazepin-2-one (t. square  220-224 0 with 1-bromo-3-chloropropane.  Output 99% of theory, t. square  6264 C.  B. Hydrochloride 1- (7,8-dimesh1-1, 3-dihydro-2H-3-benzazepin-2-one-3-yl) -3-N-methyl-N-C2- (3,4-dimethoxyphenyl) -ethyl -amino | -propane.  Prepared analogously to example 1B by the exchange reaction of 1- (7,8-dimethyl 1,3-dihydro-2H-3-benzazepin-2-one-3-Sh1) -3-chloropropane with N-methyl-2- (3, 4 -dimethoxyfensch1) -ethylamine.  Output 70.9% of theory, t. square 105107 0.  Example 45  1- (7,8-Dimethoxy-1, 3-dihydro-2H-3-benzazepin-2-one-3-yl) -2-methyl-3-N-methyl-N-C2- (3, 4-dimethoxyphenyl ) -ethyl-amino} -propane.  BUT.  1g- (7,8-Dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one-3-Sh1) -2-methyl-3-chloropropane.   Prepared analogously to example 1A by the reaction of exchange of 7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one with 1-bromo-2-methyl-3-chloropropane.  Output 97.5% of theory, t. square  4547C.  B.  1- (7,8-Dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one-3-yl) -2-metsh-3- (N-methyl-K-2- (3,4- dimethoxyphenyl) ethyl-amino} -propy.  Prepared analogously to example 1B by the reaction of exchange 1- (7,8-dimethoxy-1, 3-dihydro-2H-3-benzazepin-2-one-3-yl) -2-methyl-3-chloropropane with N-methyl-2 - (3 i 4-dimethoxyphenyl) -ethylamine.   36% of theory, t. square  30-32. WITH.  Example 46  1- (6,9-Dimethoxy-1, 3-dihydro-2H-3-benzazepin-2-one-3-yl) -3- {N-methyl-H- 2- (3,4-dimethoxyphenyl) ethyl J-amino J-propane.  BUT.  1- (6,9-Dimethoxy-1,3-dihydro-2H-3-benzazepin-2-on-3-yl) -3-chloropropane.  Prepared analogously to example 1A by the reaction of exchange of 6,9-dimethoxy, 3-dihydro-2H-3. -benzazepin-2-she (t. square : 180-191 ° C) with 1-bromo-3-chloropropane. .  Output.  27% of theory, t. pl, 9799C.  B.  1- (6,9-Dimethoxy-1,3-dihydro-2H-3-benzazepin-2-on-3-ShI) -3- {N-methyl-N- {2- (3,4-dimethoxyphenyl) - ethIz-i -amine-propane.  Prepared analogously to example 1B by the reaction of exchange 1- (6,9-dimetok. sy-, -1,3-dihydro-2H-3-benzazepin-2-one-3-.  -yl) -3-chloropropane with M-metsh1-2- (3,4-dimethoxyphenyl) -ethylamine.  Output 90% of theory.  IR spectrum (methylene chloride): 1658 cm- (CO).  Spectrum NMR (CDClI / DjO), f, h, ppm. : 2.2 (sing.  ZN (NCH,)); 3.73, 8 (4s, 12H (OCHP), 6.25 Hz).  1H (olefin).  Example 47  Hydrochloride 1- (8,9-dimethoxy-1,3-dihydrr-2H-3-.  -benzazepin-2-one-3-Sh1) -3-N-metsh1-N-2- (3,4-dimethoxyphenyl) -etip 3-aN1-propane.
    D 7;
    A. 1- (8,9-Dimethoxy-1,3-dihydro-2H 3-benzazepin-2-one-3-yl) -3-chloropropane.
    Prepared analogously to example 1A by the exchange reaction of 8,9-dimethoxy-1, 3-dihydro-2H-3-benzazepin-2-one (mp. ISS-ieS C) with 1-bromo-3-chloropropane.
    The output of 45% of theory, so pl. 677GS .B. 1- (8,9-dimethoxy-1, 3-dihydro-2H-3-benzazepin-2-one-3-yl) -3-N-methyl-N-C2- (3,4-dimethoxyphensh1) -ethyl hydrochloride -amino | -propane.
    Obtained analogously to example.1B by the reaction of exchange of 1- (8,9-dimetok si-1,3-dihydro-2H-3-benzazepin-2-one-3-one-yl) -3-chloropropane-with N-methyl- 2- (3,4-dimethoxyphenyl) ethyl amine.
    Output 64% of theory, so pl. 6468 C.
    EXAMPLE 48 1- (7 j 8-dimethoxy-1 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-M-methyl-N- dihydrochloride 2- (3,4, 3-trimethoxyphenyl) -ethylJ-amino j-propane.
    Prepared analogously to the example of BZ by the reaction of exchange of 1- (7,8-dimethoxy-1, 3,4,5-tetrahydro-2N-3-benzazepin-2-one-3-yl) -3-chloropropane with N-Methyl 2- (3,4,5-trimethoxyphenyl) ethylamine.
    The output of 44% of theory, so pl. t31 ° C (decomp.)
    EXAMPLE 49: Isomeric mixture of 1- (7, B-dimethoxy-1,3,4,5-tetrahydro. 2H-3-benzazepin-2-one-3-yl) -3- {N -Methyl-N- 2- (2- and 4-nitrophenyl) -ethyl-amino-propane
    Prepared analogously to example 1B from 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-Sh1) -3-chloropropane and N-methyl-2- ( 2- and 4-nitrophenyl) -ethylamine.
    Yield 72% of theory, IR spectrum (methylene chloride): 1659 (CO).
    Example 50. 1- (7,8-Dinetoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-1, 2-dione 3-yl) -3-N-methyl-L-2- (4 -amino-3, 5-dichlorophenyl) -ethyl J-aminoJ-propane.
    Prepared analogously to Example 2B from .1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-N-methyl-N-2- (4-amino-3,5-dichlorophenyl) -ethyl-amino propane and selenium dioxide.
    M.p. 118-130 ° C. M / e 493/495 (Ci HzeCizNjO; 494.43).
    6093518.
    Example 51. 1- (7,8-Dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-Sy-methyl-H-12- (3- amino-4-chlorophenyl) ethyl-amino-5-propane.
    Prepared analogously to example 9 by the exchange reaction of H-C3- (7,8-dimethoxy-1, 3,4,5-tetrahydro-2H-3 benzazepin-2-one-3-W1) -propyl-methylamine 0 and 2- ( 3-amino-4-chlorophenyl) ethyl chloride. Butter.
    UV spectrum (ethanol), nm: 238 (0.26) i 285 (0.13); 304 (0.06).
    5 IR spectrum (dichloromethane),: 3390 and 3480 (Shg); 1650 (CO); . 2830 (OSSN) 2795 (); 1520 and 1620 ().
    PRI me R 52. 1- (7,8-Dimetok0 si-1,3,4,5-tetrahydro-2H-3-benzazPIN-2-OH-3-Sh1) -3- {N-methyl- N- 2- (2-amino-3, 5-dichlorfensh1) -ethyl-amino J-propane.
    Prepared analogously to example 1B 5 by exchange reaction of 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-chloropropane with (2-amino -3, 5-dichlorophenyl) -ethyl-methylamine. Butter.
    0 UV spectrum (ethanol),, c 240 (0-, 34) V 285- (0.14); 306 (0.10).
    IR (dichloromethane), cm: 2810 (N-alkyl) i 2840 () -, 1655 () -, 1520 and 1620 ().
    1- (7,8-dimethoxy-2, 3,4,5-tetrahydro-1H-benzazepin-3 -yl) -3-N-methyl-H-2- (3,4-dimethoxyphenyl) ethyl 3- dihydrochloride amino} -propane. M.p. 0 270-271 c) dec.
    Hydrochloride 1 -; (7,8-dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- | N-metsh1-N- | 2- (4-methoxyphenyl) -ethylZ-amino-propane. 5: mp. 175-177 C.
    1- (7,8-methylenedioxy -1, 3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3-N-methyl-N- 2- (3,4- dimethoxyphenyl) ethyl j-amino propane. 0 m.p. 210-212 ° C.
    1- (7,8-dimethoxy-1,3,. 4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-N-methyl-N-2 hydrochloride (3,4- methylenedioxyphenyl) ethyl-aMiiHoV propane. 5 m.p. t91-193C.
    1- (7,8-dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2: -on-3-yl) -3-Gy-2- (3,4-dimethoxyphenyl) hydrochloride -ethyl-amino-propane. Mp.152154 “C,
    1- (7,8-dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-oi-3-yl) -3- {N-allyl-H- 2- (3,4 -dimethoxyphenyl) -ethyl-a.mino j-propane. T.SH1. 153-155 ° C. 1- (7,8-dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2.-One-3-yl) -3-N-propyl-N- hydrochloride 2- (3,4-dimethoxyphenyl) ethyl 3-amino propane. M.p. (dec)
    1- (7,8-dimethoxy-1,3, 4,5-tetrahydro-2H-3-benzazepin-1,2-dione-3-Sh1) -3- {K-methyl-H-C2- (3 , 4-dimethoxyphenyl) -eth-1D-amino-propane. M.p. 196-197 C.
    1- (7-Benzyloxy-8-methoxy-1, 3,4,5-tetrahydro-211-3-benzazepin-2-one-3-yl) -3-HY-methyl-M- {2- (3 , 4-dimethoxyphenyl) -ethyl-amino-5-propane. M.p. 117-120C.
    Example 53. 1- (7-hydroxy-8-methoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) hydrochloride-3- {m-methyl-N-2 - (3,4-dimethoxyphenyl) -ethyl-amino}: - propane.
    Prepared analogously to example 52 from 1- (7-benzyloxy-8-methoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- {K-methyl-H hydrochloride -; 2- (3,4-dimethoxyphenyl) -ethyl-amino-propane by catalytic debenzylation. Output 45.2% of theory.
    Found,%: C 63.15, H 7.57, N 5.64.
    CjsHj NjOy-HCl (479.0)
    Calculated,%: C 62.69, H 7.36, N 5.85.
    Example 54. 1- (7-Methoxy-8-hydroxy-C 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- {N-methyl-H-12- ( 3, 4-dimethoxyphensh1) ethylZ-amino propane.
    Prepared analogously to example 52 of 1- (7-methoxy-8-benzyloxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- {N-trashl-N- : 2- (3,4-dimethoxyphenyl) ethyl 3-amino propane by catalytic debenzylation.
    Output 29.4% of theory. .
    G-spectrum (methylene chloride). 1640 cm- (C O).
    Found,%: C 67.50, H 7.97,
    N 6.18 ..
     (442.56)
    Calculated,% :. C 67.85; H, 7.72; N, 6.38.
    1- (7,8-dimethyl-1,3, 4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- {K-methyl-H-G2-C3, 4- dimethoxyphenyl) -STmiJ -amino} -propane. M.p. 154-157C.
    1 - (7,8-Dimethoxy-1, 3-dihydro-2H-3-benzazepin-2-one-3-yl) -3-metsh-3-N-methyl-N-G2- (3,4-dimethoxyphene ) ethyl-amino-propane. M.p. 30-32 C.
    1- (7,8-dimethoxy-1,3, 4,5-tetrahydro-2H-3-benzazepin-2-one-3-sh1) hydrochloride -2-methid-3- {n-methyl-K-C2- (3,4-dimethoxyphenyl) -ethyl-amino} -proane. M.p. 99-101 €. .
    1- (6,9-Dimethoxy-1,3-dihydro-2H-Ztbenzazepin-2-one-3-yl) -3-K-metnN-2- (3,4-dimethoxyphenyl) ethyl-amio-propane.
    IR spectrum (methylene chloride):
    1658 cm- (COV,. Spectrum-NMR CBC1 / 0), h / million:
    2.2 (syng. Ts (ksnz)); 3.7-3.8 (4s, 12H (OCHj)), 6.25 G (Hz) ,. 1H (olefin) J.
    1- (6,9-dimethoxy-1,3, 4,5-tetrahydro-2H-benzazepin-2-one-3-yl) -3- {1h-methyl-H-12- (3,4-dimethoxyphenyl) hydrochloride ) -ethylJ-aminoI-propane. Mp 73-76 ° C.
    1- (8,9-dimethoxy-1, 3-dihydro-2H-3-benzazepin-2-one-3-yl) -3- {K-methyl-K-2- (3,4-dimethoxyphenyl) - ethyl amino 1-prop on. M.p. 64-.
    1- (8,9-dimethoxy-1,3, 4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- {N-methyl-L- 2- (3, 4-dimethoxyphenyl) ethyl-amino Z-propane. M.p. TZZZZS.
    1- (7,8-dimethoxy-1, 3,4,5-tetrahydroO7-2H-3-benzazepin-2- -on-3-yl) -3- {N-m-N- 2- (3, 4,5-trimethoxyphenyl) -ethyl-amino-propane. M.p. (dec)
    Example 55. 1- (7,8-Dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-N-methyl-Y- .2- (4 -aminophenyl) -ethyl-amino} propane.
    4.85 g (0,0107 mol) of 1- (7,8-dime toxi-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3-y-methyl -H- 2- (4-acetylaminophenyl) ethyl 3-amino5 propane was stirred for 34 hours with 80 ml of methanolic hydrochloric acid. After concentration of the solution, the residue was dissolved in methylene chloride, extracted with sodium bicarbonate solution and washed with water. The organic phase is dried, concentrated in vacuo and the resulting oil is dried under vacuum at 50 ° C. 88% of theory. 1 - (7,8-Dimethoxy-1,3,4-, 5-tetragi-ro-2H-1,3-benzazepin-2-one-3-yl) -3- {n-methyl-K-2- ( 4-amino-3,5dichlorophenyl) ethyl-amino 3-propane, mp.16. 1- (7,8-Dimethoxy-1,3,4,5-tetragi ro-2H-3-benzazepin-2-one-3-yl) -3-N methyl-N-12- (4-dimethylamino-3 , .5-dichlorophenyl) -ethylJ-amino V-npgnaH, IR spectrum (methylene chloride): 1650). UV spectrum (ethanol), I change to c 227 (shoulder, 0.16) j 280 (0.12). 1- (7-, 8-dimethoxy-1,3 hydrochloride 4.5-1 tetrahydro-2H-3-benzazepin-2-one-3-yl) 2- (4-amino-3,5-dichlorophenyl) ethyl - amino propane. M.p. 236-241 0. 1- (7,8-Dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- {m-etsh1-Y-G2 - (4-amino-3,5-dibromophenyl-ethyl 3-amino-propane. IR spectrum (methylene chloride), m: 3380, 3480 (NHz); 1645 (CO). UV spectrum (ethanol), / 1 A , s (ks, nm 240 (shoulder, 0.13), 280-2 90 (0.04). 1 .- (7,8-Dimethoxy-1, 3,4, 5g tetoagid ro-2H-3-benzazepine -2-one-3-Sh1) -3- {n-methyl-L-C2- (4-amino-3-chloro-5-. -Fluorophenyl) ethyl-3-amino} -propan. M / e - 463 / 365 (C24HzlCl1RoZOz; 463.99). X-.- .. 1- (7,8-Dimethoxy-1,3,4,5-tetrahyd ro-2H-3-benzazepin-2-one-3-yl) - 3- N-methyl-L-C2- (4-amino-3-chloro-5-methylphenyl) -ethyl-amino-propane, mp 60 (sintering, melting at 73 ° C). IR spectrum (methylene chloride), 3390, 3480 cm- (Wg); 1650 (CO). UV spectrum (ethanol), D 237. (O, 14) J 280-290 (0.05). 1- (7.8-Dimethoxy-1, 3,4,5-tetrahydro-PO-2H-1, 3-benzazepin-2-one-3-yl) -3- {s-methyl-N-C2- (3,4-dimethoxyphenyl) -etrp-amin6} propane H. 116-117 ° C Hydrochloride 1 - (7,8-dimethoxy-1,3 4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- {n-metsh1 -H- 2- (2-acetylaminophenyl) -ethylJ-amino-propane. T.pl. 102-105 C (decomp.) 1- (7,8-dimethoxy-1,3, 4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- (s-methyl-H- 2- (4-acetyl-aminophenyl) hydrochloride -ethyl-amino 1-propane, m.p. 88-93 0 (decomp.) 3522 1- (7,8-dihydroxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-g3 -yl) -3-fN-methyl-N- 2- (3,4-dimethoxyphene) I-ethyl 3-amino t-propane. IR spectrum (methylene chloride), cm-: 3520. (OH) - ,; 1640 (CO). Found,%: C 63.44, AND 7.77, N 6.13. C ,, 1/2 NZO (455.5) Calculated,%: C 63.28, H 7.74 N 6 , 15 .. Compounds of general formula (J) and their physiologically absorbable acid addition salts with inorganic or acids with valuable pharmacological properties, in particular, with negligible side effects, such as a slight antimuscarinic effect, prolonged lowering of the heart rate, action; and also action that reduces the need for the heart to 0. For example, the compounds A-dihydrochloride 1- (. 7,8-dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- {N-methyl-N- 2- (3,4-dimethoxyphenyl) - ethylJ-aminoJ-propane; B- 1- (7,8-dimethoxy-1, 3-dihydro-2H-3-benzazepine-2-on-3-yl) hydrochloride - 3-N-methyl-H-2- (3,4-dime toxylphenyl ) -ethyl J-amino-propane, B-hydrochloride of 1- (7,8-dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-1, L., L. .. l. "( .d, "hch, |" m -dione-3-yl) -3- {N-methyl-C2- (3,4-dimethoxyphenyl) -ethyl-amino-propane} G - 1- (7,8-dimethoxy -1,3,4,5-tetrahydro-2H-1, 3-benzdiazepin-2-one-3-yl) -3 - f N-methyl-C2- (3,4-dimethoxyPhenkl) -ethyl-amino propane ; D - hydrochloride 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- {N- 2- (3,4- dimethoxyphensh1) ethyl-amino-propaneJE - 1- (7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl) -3- | s Etil-N- 2- (4-amino-3,5-dichlorofensh1) -ethyl j-amino | -propane; W - hydrochloride 1- (7,8-dimethoxy-1, 3-dihydro-2H-3-benzazepine- 2-he-3-yl) -3-tN-methyl-N- (2- (4-methoxyphenyl) -ethyl) amino-propane-, 3 - 1- (7,8-dimethoxy-1, 3, hydrochloride, 4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl) -3- {N-mitshl-N-2- (4-methoxyphenyl) -ethyl-amino-propane; And - hydrochloride 1- ( 7,8-methylenedioxy-1, 3,4,5-tetrahydro-2H-3-benz23;
    azepin-2-one-3-yl) -3-N-MeTHJi-N-2- (3,4-dimethoxyphenyl) ethyl-amino-propyn;
    K - hydrochloride, 8-dimethoxy-1, 3,4,5-tetrahydro-2H-3-benzazepin-2-one-3-yl-3-tN-allyl-N- (2- (J, 4-dimethoxyphenyl) -ethyl) -amino-propane,
    L - 1- (7,8-dimethoxy-1, 3-dihydro-2H-3-benzazepin-2-one-3-yl) -3-N-methyl-Y-2- (3,4-methylenedioxyphenyl) hydrochloride -ethylJ-aMHHol-propane,
    the results of which are compared with the corresponding properties of known compounds
    M - 1- (7,8-dimethoxy-1, 2,3,4-tetrahydro-5H-2-benzazepin-1-OH-2-Sh1) -3- {n-methyl-Y- (2- ( 3,4-dimethoxyphensh1) ethyl) amino-propane,
    H - 1- (6,7-dimethoxy-3, 4-dihydro-2H-isoquinolin-1-one-2-yl) -3-N-methyl-N- 2- (3,4-dimethoxyphenyl) -ethyl hydrochloride -amino-propane.
    The research is carried out on the following steps.
    Decrease in heart rate,% -55
    Half-life, min 120
    The effect of the proposed compounds on the heart rate in the atrium in the guinea pig.
    Isolated, spontaneously bored atria of guinea pigs of both sexes weighing 300-400 g are examined in a special bath in Tyrode solution. The nutrient solution is supplied with carbogen (95% Oj + 5% CO) and kept invariably at. Abbreviations are recorded isometrically using a strain gauge with an ohmic sensor at 6093524
    The effect of the proposed compounds on the heart rate in cats.
    The study of the effect of the proposed substances on the heart rate was carried out on 7 cats of both sexes weighing from 2.5 to 3.5 kg. by giving the substance on the dose to the animal. For this, cats are anesthetized with Nembutal (30 mg / kg, intraperitoneally) and hloralose-urethane (40 mg / ml chloralose + 200 mg / mp urethane on demand). The test substance is injected in the form of an aqueous 5 solution into the latent vein or duodenum. Heart rate
    abbreviations are recorded before and after giving a substance using the Grass tachograph from an electrocardiogram (chest discharge) on the Grass polygraph. Table 1 summarizes the results obtained in the study of substances taken at a dose of 1.0 mg / kg (intravenously).
    Table 1
    -51 -8.2
    -32,0
    120 13 25
    Ligraf Grasse. The test substances are administered in special glands with organs.
    with a duration of 60 minutes in various concentrations.
    Based on the maximum data, the curves of action of various concentrations h are determined. From these data, those concentrations that reduce the frequency of contractions by 30% (EC 60so) are determined.
    Table 2 summarizes the findings of the study. EC 60jtt (- ,, mg / ml 0.030 O, Q97 0.058 0.066 0.014
    The acute toxicity of the test compounds is tested on mice (observation time: 14 days) after intravenous administration.
    When tested, substance A toxicity (LDyg) is 89 mg / kg intravenously and 1350 mg / kg n.o.i.
    table 2
    On the basis of their pharmacological properties, the compounds obtained according to the invention are suitable for treating sinus tachycardias of various genesis and for the prevention and treatment of heart diseases caused by local anemia. 0.014 0.0079 0.063 0.050 0.014
    权利要求:
    Claims (4)
    [1]
    1. A method for producing benzazepine derivatives of the general formula wherein the alkyl group may contain 1-3 carbon atoms, or one of these radicals may also mean a hydrogen atom, or both radicals together may form an alkylenedioxy group with 1 or 2 carbon atoms',
    Rj and - the same or different g, mean hydrogen or halogen, hydroxyl, alkyl or alkoxy groups with 1 to 4 carbon atoms, trifluoromethyl, cyano or one of these radicals can also mean a nitro group, or both radicals together can form an alkylenedioxy group with 1 or 2 atoms carbon;
    R 5 is a hydrogen atom, alkoxy, amino with but-, dialkylamino, alkoxycarbonylamino or trifluoroethylamino
    R t - hydrogen, alkyl with 1-3 carbon atoms, benzyl or allyl, and their acid additive salts with inorganic acids and
    - I mean that, by the formulas I distinguish the compound where A is the group —CH g —CH 2 -, —CH = CH—,
    R
    -NH-CO- or ~ C = N ~, in which R - al — Y y · a alkyl group with the number of carbon atoms 1-3;
    B is a methylene or carbonyl group;
    E is an ethylene or m-propylene group;
    G is an ethylene group,
    R, and Rj, the same or different, mean hydroxyl, alkyl, alkoxy or phenylalkoxy groups, in coSU „„ 1160935 halogen, group
    R, and have the indicated
    A, B, E, meanings;
    U is an —NH atom, where R fi has the indicated meaning, or together with a hydrogen atom in position p of the radical E is an oxygen atom, is reacted with a compound of the general formula p where G, R 3 , R 4 and R g have the indicated meanings;
    V is a halogen atom or a group —NH, where Rg has the indicated meaning, wherein V is different from U, with the subsequent isolation of the target product in free form or in the form of a salt ..
    [2]
    2. The method according to claim 1, characterized in that the reaction is carried out in a solvent environment. ·
    [3]
    3. The method of pops 1 and 2, characterized in that the reaction is carried out in the presence of a base.
    [4]
    4. The method according to claims 1-3, characterized in that the reaction is carried out at a temperature ranging from the boiling point of the solvent used to 140 about C.
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    ES8308312A1|1983-08-16|
    JPS57193462A|1982-11-27|
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    KR830010077A|1983-12-26|
    ES517756A0|1983-08-16|
    BG60412B2|1995-02-28|
    EP0065229A1|1982-11-24|
    JPH0136829B2|1989-08-02|
    DE3265206D1|1985-09-12|
    AU8379482A|1982-11-25|
    FI821724A0|1982-05-17|
    PT74919B|1985-05-16|
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    ES8306726A1|1983-06-01|
    ES517753A0|1983-08-16|
    YU44674B|1990-12-31|
    HK43388A|1988-06-17|
    KR890001544B1|1989-05-08|
    NO159166B|1988-08-29|
    KR890001550B1|1989-05-08|
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    ZA823413B|1984-01-25|
    YU105182A|1986-12-31|
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    ES8308309A1|1983-08-16|
    DK156720B|1989-09-25|
    CS410291A3|1992-08-12|
    IL65814D0|1982-08-31|
    GB2099425A|1982-12-08|
    AU551509B2|1986-05-01|
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    申请号 | 申请日 | 专利标题
    DE19813119874|DE3119874A1|1981-05-19|1981-05-19|"BENZAZEPINE DERIVATIVES, THEIR PRODUCTION AND THEIR USE AS MEDICINAL PRODUCTS"|
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