CH601298

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-...

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Hauptverfasser:	JOEL GILBERT BERGER, CHARLES DEWITT ADAMS
Format:	Patent
Sprache:	eng
Schlagworte:	APPARATUS THEREFOR CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOIDCHEMISTRY CHEMISTRY GENERAL METHODS OF ORGANIC CHEMISTRY HETEROCYCLIC COMPOUNDS METALLURGY ORGANIC CHEMISTRY PERFORMING OPERATIONS PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL THEIR RELEVANT APPARATUS TRANSPORTING
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creator	JOEL GILBERT BERGER CHARLES DEWITT ADAMS
description	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 Ra, 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 R2 is as Ra or methoxymethyl or -COR7, in which R7 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;
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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 Ra, 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 R2 is as Ra or methoxymethyl or -COR7, in which R7 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 R6, which is methyl; ethyl; benzyl; benzyl ring- substituted by chloro, methyl or methoxy; or cyclopropylmethyl, with a compound of the general formula ClCOOR3, wherein R3 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 R3 is benzyl or substituted benzyl, to hydrolysis or hydrogenolysis; (c) when R is Rc, 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) RcZ, wherein Z is Cl, Br, I or -OS(O) 2 R8, in which R8 is CH 3 , phenyl or p-tolyl, or (ii) wherein R9 is C 1 -C 4 alkyl, in the presence of an acid acceptor; (d) when R is Rd, 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 QCOR4, wherein R4 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 R5 is different from R4 and is C 1 -C 4 alkyl, provided that when R4 is hydrogen, R5 is methyl; and R6 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 R2 is methoxymethyl, by reacting the corresponding compound in which R2 is hydrogen with chloromethyl methyl ether; (b) when R2 is hydrogen, benzyl or -COR7, by condensing 5 - amino - 10,11 - dihydro - 5H - dibenz- [b,f]azepine with 4-piperidone, optionally 1- substituted by benzyl or -COR7, in the presence of an acid; (c) when R2 is -CH 2 R7, by reducing the corresponding compound in which R2 is -COR7; and (d) when R2 is -COR7, by acylating the corresponding compound in which R2 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.</description><language>eng</language><subject>APPARATUS THEREFOR ; CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOIDCHEMISTRY ; CHEMISTRY ; GENERAL METHODS OF ORGANIC CHEMISTRY ; HETEROCYCLIC COMPOUNDS ; METALLURGY ; ORGANIC CHEMISTRY ; PERFORMING OPERATIONS ; PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL ; THEIR RELEVANT APPARATUS ; TRANSPORTING</subject><creationdate>1978</creationdate><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://worldwide.espacenet.com/publicationDetails/biblio?FT=D&date=19780714&DB=EPODOC&CC=CH&NR=601298A5$$EHTML$$P50$$Gepo$$Hfree_for_read</linktohtml><link.rule.ids>230,308,776,881,25543,76293</link.rule.ids><linktorsrc>$$Uhttps://worldwide.espacenet.com/publicationDetails/biblio?FT=D&date=19780714&DB=EPODOC&CC=CH&NR=601298A5$$EView_record_in_European_Patent_Office$$FView_record_in_$$GEuropean_Patent_Office$$Hfree_for_read</linktorsrc></links><search><creatorcontrib>JOEL GILBERT BERGER</creatorcontrib><creatorcontrib>CHARLES DEWITT ADAMS</creatorcontrib><title>CH601298</title><description>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 Ra, 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 R2 is as Ra or methoxymethyl or -COR7, in which R7 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 R6, which is methyl; ethyl; benzyl; benzyl ring- substituted by chloro, methyl or methoxy; or cyclopropylmethyl, with a compound of the general formula ClCOOR3, wherein R3 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 R3 is benzyl or substituted benzyl, to hydrolysis or hydrogenolysis; (c) when R is Rc, 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) RcZ, wherein Z is Cl, Br, I or -OS(O) 2 R8, in which R8 is CH 3 , phenyl or p-tolyl, or (ii) wherein R9 is C 1 -C 4 alkyl, in the presence of an acid acceptor; (d) when R is Rd, 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 QCOR4, wherein R4 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 R5 is different from R4 and is C 1 -C 4 alkyl, provided that when R4 is hydrogen, R5 is methyl; and R6 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 R2 is methoxymethyl, by reacting the corresponding compound in which R2 is hydrogen with chloromethyl methyl ether; (b) when R2 is hydrogen, benzyl or -COR7, by condensing 5 - amino - 10,11 - dihydro - 5H - dibenz- [b,f]azepine with 4-piperidone, optionally 1- substituted by benzyl or -COR7, in the presence of an acid; (c) when R2 is -CH 2 R7, by reducing the corresponding compound in which R2 is -COR7; and (d) when R2 is -COR7, by acylating the corresponding compound in which R2 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.</description><subject>APPARATUS THEREFOR</subject><subject>CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOIDCHEMISTRY</subject><subject>CHEMISTRY</subject><subject>GENERAL METHODS OF ORGANIC CHEMISTRY</subject><subject>HETEROCYCLIC COMPOUNDS</subject><subject>METALLURGY</subject><subject>ORGANIC CHEMISTRY</subject><subject>PERFORMING OPERATIONS</subject><subject>PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL</subject><subject>THEIR RELEVANT APPARATUS</subject><subject>TRANSPORTING</subject><fulltext>true</fulltext><rsrctype>patent</rsrctype><creationdate>1978</creationdate><recordtype>patent</recordtype><sourceid>EVB</sourceid><recordid>eNrjZOBw9jAzMDSytOBhYE1LzClO5YXS3Azybq4hzh66qQX58anFBYnJqXmpJfEw5Y6mxoRVAACJ1Bni</recordid><startdate>19780714</startdate><enddate>19780714</enddate><creator>JOEL GILBERT BERGER</creator><creator>CHARLES DEWITT ADAMS</creator><scope>EVB</scope></search><sort><creationdate>19780714</creationdate><title>CH601298</title><author>JOEL GILBERT BERGER ; CHARLES DEWITT ADAMS</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-epo_espacenet_CH601298A53</frbrgroupid><rsrctype>patents</rsrctype><prefilter>patents</prefilter><language>eng</language><creationdate>1978</creationdate><topic>APPARATUS THEREFOR</topic><topic>CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOIDCHEMISTRY</topic><topic>CHEMISTRY</topic><topic>GENERAL METHODS OF ORGANIC CHEMISTRY</topic><topic>HETEROCYCLIC COMPOUNDS</topic><topic>METALLURGY</topic><topic>ORGANIC CHEMISTRY</topic><topic>PERFORMING OPERATIONS</topic><topic>PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL</topic><topic>THEIR RELEVANT APPARATUS</topic><topic>TRANSPORTING</topic><toplevel>online_resources</toplevel><creatorcontrib>JOEL GILBERT BERGER</creatorcontrib><creatorcontrib>CHARLES DEWITT ADAMS</creatorcontrib><collection>esp@cenet</collection></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>JOEL GILBERT BERGER</au><au>CHARLES DEWITT ADAMS</au><format>patent</format><genre>patent</genre><ristype>GEN</ristype><title>CH601298</title><date>1978-07-14</date><risdate>1978</risdate><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 Ra, 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 R2 is as Ra or methoxymethyl or -COR7, in which R7 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 R6, which is methyl; ethyl; benzyl; benzyl ring- substituted by chloro, methyl or methoxy; or cyclopropylmethyl, with a compound of the general formula ClCOOR3, wherein R3 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 R3 is benzyl or substituted benzyl, to hydrolysis or hydrogenolysis; (c) when R is Rc, 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) RcZ, wherein Z is Cl, Br, I or -OS(O) 2 R8, in which R8 is CH 3 , phenyl or p-tolyl, or (ii) wherein R9 is C 1 -C 4 alkyl, in the presence of an acid acceptor; (d) when R is Rd, 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 QCOR4, wherein R4 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 R5 is different from R4 and is C 1 -C 4 alkyl, provided that when R4 is hydrogen, R5 is methyl; and R6 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 R2 is methoxymethyl, by reacting the corresponding compound in which R2 is hydrogen with chloromethyl methyl ether; (b) when R2 is hydrogen, benzyl or -COR7, by condensing 5 - amino - 10,11 - dihydro - 5H - dibenz- [b,f]azepine with 4-piperidone, optionally 1- substituted by benzyl or -COR7, in the presence of an acid; (c) when R2 is -CH 2 R7, by reducing the corresponding compound in which R2 is -COR7; and (d) when R2 is -COR7, by acylating the corresponding compound in which R2 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.</abstract><oa>free_for_read</oa></addata></record>
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subjects	APPARATUS THEREFOR CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOIDCHEMISTRY CHEMISTRY GENERAL METHODS OF ORGANIC CHEMISTRY HETEROCYCLIC COMPOUNDS METALLURGY ORGANIC CHEMISTRY PERFORMING OPERATIONS PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL THEIR RELEVANT APPARATUS TRANSPORTING
title	CH601298
url	https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T04%3A03%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-epo_EVB&rft_val_fmt=info:ofi/fmt:kev:mtx:patent&rft.genre=patent&rft.au=JOEL%20GILBERT%20BERGER&rft.date=1978-07-14&rft_id=info:doi/&rft_dat=%3Cepo_EVB%3ECH601298A5%3C/epo_EVB%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true