GB1191309A - Indeno Pyridine Derivatives - Google Patents

Abstract

1,191,309. Indenopyridine derivatives. SANDOZ Ltd. 2 June, 1967 [21 June, 1966; 6 March, 1967], No. 57150/69. Divided out of 1,191,307. Heading C2C. Novel compounds II in which R 1 is H, C 1-5 alkyl, C 3-8 alkenyl or alkynyl, benzyl or phenethyl; and R 2 is H, Cl, Br, or C 1-4 alkyl and their acid addition salts, are prepared by (a) reducing the corresponding 5-oxo compound with a complex alkali metal hydride, (b) hydrogenating the corresponding 5-oxo compound in which R 1 is H, C 1-5 alkyl, or phenethyl, (c) reacting a compound II in which R 1 is H with a compound of formula R-X, where R is C 1-5 alkyl, C 3-8 alkenyl or alkynyl, benzyl or phenethyl and X is the acid radical of a reactive ester, (d) reducing a compound of Formula V or VI in which R 2 is C 1-4 alkyl or alkoxy, phenyl or benzyl and R 4 is H or -COR 3 , or (e) catalytic hydrogenation of a compound II in which R 1 is benzyl, or C 2-5 alkenyl or alkynyl, followed in any of (a)-(e) by salt formation, if desired. Intermediates isolated are 2-ethoxycarbonyl- 1,2,3,4,4a,9b - hexahydro - 5H - indeno - [1,2 - c]- pyridin-5-ol, prepared by reacting 2-methyl-5- acetoxy - 1,2,3,4,4a,9b - hexahydro - 5H - indeno- [1,2-c]pyridine (which is itself prepared by reaction of the appropriate 5-ol with acetic anhydride) with chloroformic acid ethyl ester to give 2 - ethoxycarbonyl - 5 - acetoxy- 1,2,3,4,4a,9bhexahydro - 5H - indeno[1,2-c]pyridine followed by hydrolysis; 2-benzyl-1,2,3,4,4a,9b-hexahydro- 5H - indeno[1,2-c]pyridine 5-one, prepared by cyclization of 1 - benzyl - 3 phenyl - isonipecotinic acid ethyl ester which is prepared from 1 - benzyl - 1,2,5,6 - tetrahydroisonicotinic acid ethyl ester (A) by a Gignard reaction with bromobenzene; ester A, prepared by reduction of 4 - ethoxycarbonyl - 1 - benzyl - pyridinium bromide which is prepared by heating isonicotinic acid ethyl ester with benzyl bromide; 1,2,3,4, 4a,9b - hexahydro - 5H - indeno[1,2-c]pyridin-5- one, prepared by reacting chloroformic acid ethyl ester with 2-methyl-1,2,3,4,4a,9b-hexahydro - 5H - indeno[1.2-c]pyridin-5-one followed by hydrolysis; 7-bromo-2-methyl-1,2,3,4,4a,9bhexahydro - 5H - indeno[1,2-c]pyridin- 5 - one, prepared by cyclization of 1-methyl-3-(4-bromophenyl) isonipecotinic acid methyl ester, which is prepared from 1-methyl-1,2,5,6-tetrahydro-isonicotinic acid methyl ester by a Grignard reaction with p-dibromobenzene; and 2-acetyl- 1,2,3,4,4a,9b - hexahydro - 5H - indeno[1,2c]- pyridin-5-ol, prepared by reacting the 2-unsubstituted compound with acetic anhydride.