DECAHYDROISOQUINOLINES

摘要

1513301 1 - Alkenyl - 3α - phenyl - perhydroisoquinolines ELI LILLY & CO 2 May 1975 [7 May 1974] 18322/75 Heading C2C Novel compounds of the Formula I wherein R is -C(R11)(R111)-C 2-5 alkenyl in which R11 and R111 are independently H, methyl or ethyl, provided that R has less than 7 carbon atoms and R1 is OH, alkoxy or alkanoyloxy in which the alkyl groups have 1 to 3 carbon atoms and pharmaceutically acceptable acid addition salts thereof, may be prepared by reacting a compound I in which R is hydrogen with RX where X is halogen when R 1 is OH or alkoxy, optionally followed where R 1 is OH by alkylation or esterification to produce compounds I in which R 1 is alkoxy or alkanoyloxy. 3a(m - Methoxyphenyl) 1, 2, 3, 3a, 4, 5, 6, 7, 7a, 8- decahydroisoquinoline is prepared reacting 2-(mmethoxyphenyl)cyclohexanone with acrylonitrile to form 2 - (# - cyanoethyl) - 2 - (mmethoxyphenyl)cyclohexanone, which is hydrolysed to 2 - (2 - carboxyethyl) - 2 - (m-methoxyphenyl)cyclohexanone, which is reacted with phenyl chloroformate followed by sodium azide to form the azide of the above acid, which is subjected to Curtius conditions to yield 2-(2- isocyanatoethyl) - 2 - (m - methoxyphenyl)cyclohexanone, which on treatment with acid cyclises to 3a-(m-methoxyphenyl)-2,3,3a,4,5,6,7- heptahydroindole, which is methylated in the 1-position to yield 1-methyl-3a(m-methoxy phenyl) - 1,2,3,3a,4,5,6 - heptahydroindole, which is converted to its quaternary fluoroborate and then treated with diazomethane to yield 1 - azonia - 1 - methyl - 4 - (m - methoxyphenyl)- tricyclo[4,2,1,01-9]decane as its fluoroborate salt, which on heating yields 1 - methyl - 3a- (m - methoxyphenyl) - 1,2,3,3a,4,5,6,7 - octahydroisoquinoline, which is hydrogenated to the decahydroisoquinoline, which is purified as its picrate salt. The decahydro isoquinoline is demethylated by reaction with phenyl chloroformate to yield 1-phenyl-carboxy-3a-(m-methoxyphenyl) - 1,2,3,3a,4,5,6,7,7a,8 - decahydroisoquinoline, which with acid and then strong base yields the required compound. 3a - (m - Hydroxyphenyl) - 1,2,3,3a,4,5,6,7,7a,8- decahydroisoquinoline is prepared either by demethylation of the corresponding m-methoxy compound or by demethylation of 1-methyl-3a- (m - methoxyphenyl) - 1,2,3,3a,4,5,6,7,7a,8 - decahydroisoquinoline to yield 1 - methyl - 3a - (mhydroxyphenyl) - 1,2,3,3a,4,5,6,7,7a,8-decahydroisoquinoline, followed by removal of the 1- methyl group as in the previous paragraph. Compounds of the Formula I in which R1 is hydroxy or C 1-3 alkoxy and R is H are the subject of Specification 1,513,303 and the cis compounds when R is methyl are the subject of Specification 1,513,302. Pharmaceutical compositions of the compounds I with the usual excipients show analgetic agonistic and analgetic antagonistic activity when administered parenterally or orally.