GB1449331A - Benzazepine derivatives - Google Patents

Benzazepine derivatives

Info

Publication number
GB1449331A
GB1449331A GB265774A GB265774A GB1449331A GB 1449331 A GB1449331 A GB 1449331A GB 265774 A GB265774 A GB 265774A GB 265774 A GB265774 A GB 265774A GB 1449331 A GB1449331 A GB 1449331A
Authority
GB
United Kingdom
Prior art keywords
methyl
substituted
chloro
hydrogen
benzyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
GB265774A
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
ENDO LAB
Original Assignee
ENDO LAB
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US359504A external-priority patent/US3890327A/en
Priority claimed from US05/422,616 external-priority patent/US3932650A/en
Application filed by ENDO LAB filed Critical ENDO LAB
Priority to GB2974876A priority Critical patent/GB1521792A/en
Publication of GB1449331A publication Critical patent/GB1449331A/en
Expired legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
    • C07D471/16—Peri-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

1449331 Octahydropyridoindolobenzazepines ENDO LABORATORIES Inc 21 Jan 1974 [22 Jan 1973 11 May 1973 6 Dec 1973 (2)] 02657/74 Heading C2C Novel octahydropyridoindolobenzazepines of the general formula n is zero or one; X is an anion of a pharmaceutically suitable acid; and R is hydrogen; 3-chloro-2-butenyl; 2-bromoallyl; benzyl; benzyl ring-substituted with methyl, methoxy or chloro; phenethyl; 3-phenylpropyl; 3-phenylpropyl ring substituted with chloro, bromo or methoxy; furfurtyl; 2-thenyl; acetonyl; phenacyl; C 1 -C 5 , alkyl; C 3 -C 5 alkenyl; C 3 -C 5 alkynyl; cinnamyl; cinnamyl ring-substituted with chloro, bromo, or methoxy; 3-phenyl-2- propynyl; cyclopropyl ; C 4 -C 8 cycloalkylmethyl (methylcyclopropyl)methyl; (cis - 2,3 - dimethylcyclopropyl)methyl; C 6 -C 8 cyclo = alkenylmethyl; C 6 -C 8 cycloalkadienylmethyl; (2,3-dimethylcycloprop- 2 - en - 1 - yl)methyl; exo - 7 - norcarylmethyl; (cis - 1,6 - dimethylendo - 3 - norcaren - 7 - yl)methyl; (4 - methylbicyclo[2.2.2]oct - 1 - yl)methyl; (4 - methylbicyclo[2.2.2]oct - 2 - en - 1 - yl) methyl; (bicyclo[2.2.1]hept - 2 - yl)methyl; bicyclo[2.2.1]- hept - 2 - en - 5 - yl)methyl; 1 - adamantylmethyl; or 2 - adamantylmethyl, and the hydrogens in the 4a and 14a positions are in trans relationship to each other, are prepared (a) when R is R<SP>a</SP>, which is benzyl; benzyl ring- substituted with methyl, methoxy or chloro; phenethyl; 3 - phenylpropyl; 3 - phenylpropyl ring-substituted by chloro, bromo or methoxy; furfuryl; 2-thenyl; C 1 -C 5 alkyl; cyclopropyl; C 4 -C 8 cycloalkylmethyl; (methyl-cyclopropyl)- methyl; exo - 7 - norcarylmethyl; (4 - methylbicyclo[2.2.2]oct - 1 - yl)methyl; (bicyclo- [2.2.1]hept- 2 - yl)methyl; 1 - adamantylmethyl; or 2 - adamantylmethyl, by reducing with a boron hydride/tetrahydrofuran complex a hexahydro pyridoindolobenzazepine of the general formula wherein R<SP>2</SP> is as R<SP>a</SP> or methoxymethyl or -COR<SP>7</SP>, in which R<SP>7</SP> is phenyl; chlorophenyl; methylphenyl; methoxyphenyl; benzylphenethyl; phenethyl ring - substituted by chloro, bromo or methoxy; 2-furyl; 2-thienyl; hydrogen; C 1 -C 4 alkyl; C 2 -C 4 alkenyl; styryl; styryl ring - substituted by chloro, bromo or methoxy; C 2 -C 7 , cycloalkyl; methylcyclopropyl; C 5 -C 7 cycloalkenyl; C 5 -C 7 cycloalkadienyl; exo - 7 - norcaryl; 4 - methylbioyclo- [2.2.2]oct - 1 - yl; bicyclo[2.2.1]hept - 2 - yl; 4 - methyl - bicyclo[2.2.2]oct - 2 - en - 1 - yl; bicyclo[2.2.1]hept - 2 - en - 5 - yl; 1 - adamantyl; or 2 - adamantyl; followed by acidification; (b) when R is hydrogen, by reacting the corresponding compound in which R is R<SP>6</SP>, which is methyl; ethyl; benzyl; benzyl ring- substituted by chloro, methyl or methoxy; or cyclopropylmethyl, with a compound of the general formula ClCOOR<SP>3</SP>, wherein R<SP>3</SP> is C 1 -C 4 alkyl; vinyl; benzyl; p-methylbenzyl; p-methoxybenzyl; or phenyl, and subjecting the resulting ester of the general formula to hydrolysis or, when R<SP>3</SP> is benzyl or substituted benzyl, to hydrolysis or hydrogenolysis; (c) when R is R<SP>c</SP>, which is as R with the exception of hydrogen, cyclopropyl and (cis-2,3-dimethylcyclopropyl)methyl, by alkylating the corresponding compound in which R is hydrogen with a compound of the general formula (i) R<SP>c</SP>Z, wherein Z is Cl, Br, I or -OS(O) 2 R<SP>8</SP>, in which R<SP>8</SP> is CH 3 , phenyl or p-tolyl, or (ii) wherein R<SP>9</SP> is C 1 -C 4 alkyl, in the presence of an acid acceptor; (d) when R is R<SP>d</SP>, which is as R with the exception of hydrogen, acetonyl, phenacyl, cyclopropyl, cinnamyl, substituted cinnamyl, 3-phenyl-2-propynyl and (cis-2,3- dimethylcyclopropyl)methyl, by acylating the corresponding compound wherein R is hydrogen with a compound of the general formula QCOR<SP>4</SP>, wherein R<SP>4</SP> is 2-chloro-1-propenyl; 1- bromovinyl; phenyl; chlorophenyl; methylphenyl; methoxyphenyl; benzyl; phenethyl; phenethyl ring-substituted with chloro, bromo, or methoxy; 2-furyl; 2-thienyl; hydrogen; C 1 -C 4 -alkyl; C 2 -C 4 alkenyl; C 2 -C 4 alkynyl; styryl; styryl ring substituted with chloro, bromo, or methoxy; phenylethynyl; C 3 -C 7 cycloalkyl; methylcyclopropyl; C 5 -C 7 cycloalkenyl; C 5 -C 7 cycloalkadienyl; 2,3-dimethylcycloprop - 2 - en - 1 - yl; exo - 7 - norcaryl; cis - 1,6 - dimethyl - endo - 3 - norcaren - 7 - yl; 4 - methyl - bicyclo[2.2.2]oct - 1 - yl; bicyclo- [2.2.1]hept - 2 - yl; 4 - methylbicyclo[2.2.2]- oct - 2 - en - 1 - yl; bicyclo - [2.2.1]hept - 2 - en- 5 - yl; 1 - adamantyl; or 2 - adamantyl; Q is -Cl, -Br, C 1 -C 4 alkoxy; or R<SP>5</SP> is different from R<SP>4</SP> and is C 1 -C 4 alkyl, provided that when R<SP>4</SP> is hydrogen, R<SP>5</SP> is methyl; and R<SP>6</SP> is C 1 -C 4 alkyl; and reducing the resulting ketone of the general formula with a metal hydride; and (e) when R is (cis- 2,3-dimethylcyclopropyl)methyl, by catalytically hydrogenating the corresponding compound in which R is (2,3-dimethylcycloprop-2-en-1-yl)- methyl; followed optionally by salification of a resulting free base. Hexahydropyridoindolobenzazepines of the second general formula above are prepared (a) when R<SP>2</SP> is methoxymethyl, by reacting the corresponding compound in which R<SP>2</SP> is hydrogen with chloromethyl methyl ether; (b) when R<SP>2</SP> is hydrogen, benzyl or -COR<SP>7</SP>, by condensing 5 - amino - 10,11 - dihydro - 5H - dibenz- [b,f]azepine with 4-piperidone, optionally 1- substituted by benzyl or -COR<SP>7</SP>, in the presence of an acid; (c) when R<SP>2</SP> is -CH 2 R<SP>7</SP>, by reducing the corresponding compound in which R<SP>2</SP> is -COR<SP>7</SP>; and (d) when R<SP>2</SP> is -COR<SP>7</SP>, by acylating the corresponding compound in which R<SP>2</SP> is hydrogen. Pharmaceutical compositions having analgesic and sedative-tranquillizer activity comprise, as active ingredient, at least one pyridoindolobenzazepine of the first general formula above, together with a pharmaceutically suitable vehicle.
GB265774A 1973-01-22 1974-01-21 Benzazepine derivatives Expired GB1449331A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
GB2974876A GB1521792A (en) 1973-01-22 1976-07-16 Benzazepine derivatives and pharmaceutical compositions containing them

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US32535273A 1973-01-22 1973-01-22
US359504A US3890327A (en) 1973-05-11 1973-05-11 Trans-1,2,3,4,4a,8,9,14a-octahydropyrido(r',3':2,3)indolo(1,7-ab)+8 1)benzazepine
US42261573A 1973-12-06 1973-12-06
US05/422,616 US3932650A (en) 1973-01-22 1973-12-06 Trans-octahydropyridoindolobenzazepines as central nervous system depressants

Publications (1)

Publication Number Publication Date
GB1449331A true GB1449331A (en) 1976-09-15

Family

ID=27502310

Family Applications (1)

Application Number Title Priority Date Filing Date
GB265774A Expired GB1449331A (en) 1973-01-22 1974-01-21 Benzazepine derivatives

Country Status (18)

Country Link
JP (1) JPS49108100A (en)
AR (1) AR207113A1 (en)
AT (1) AT340429B (en)
BE (1) BE809977A (en)
CA (1) CA993872A (en)
CH (1) CH601298A5 (en)
DD (1) DD111906A5 (en)
DE (1) DE2402391A1 (en)
FR (1) FR2214478B1 (en)
GB (1) GB1449331A (en)
HU (1) HU169309B (en)
IE (1) IE38775B1 (en)
IL (1) IL44042A (en)
LU (1) LU69210A1 (en)
NL (1) NL7400849A (en)
NO (1) NO140822C (en)
PH (1) PH11128A (en)
SE (1) SE407802B (en)

Also Published As

Publication number Publication date
DE2402391A1 (en) 1974-07-25
NL7400849A (en) 1974-07-24
FR2214478A1 (en) 1974-08-19
IL44042A (en) 1977-02-28
CA993872A (en) 1976-07-27
HU169309B (en) 1976-11-28
SE407802B (en) 1979-04-23
AR207113A1 (en) 1976-09-15
AT340429B (en) 1977-12-12
PH11128A (en) 1977-10-27
IE38775L (en) 1974-07-22
LU69210A1 (en) 1975-04-11
NO140822B (en) 1979-08-13
NO140822C (en) 1979-11-21
IL44042A0 (en) 1974-05-16
NO740177L (en) 1974-07-23
IE38775B1 (en) 1978-05-24
AU6470774A (en) 1975-07-24
BE809977A (en) 1974-07-22
CH601298A5 (en) 1978-07-14
ATA50074A (en) 1977-04-15
FR2214478B1 (en) 1978-01-13
JPS49108100A (en) 1974-10-14
DD111906A5 (en) 1975-03-12

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Legal Events

Date Code Title Description
PS Patent sealed [section 19, patents act 1949]
PCNP Patent ceased through non-payment of renewal fee