GB1374337A - Aminoalkylisochromans and -isocoumarins - Google Patents

Abstract

1374337 Aminoalkyl-isochromans and iso- COumarins SANDOZ Ltd 14 March 1972 11830/72 Heading C2C Novel compounds of the Formula (I) wherein each R independently denotes H, CF 3 , or C 1-5 alkyl or alkoxy, each R 1 independently denotes H, F, Cl, CF 3 or C 1-5 alkyl or alkoxy, or two R 1 's on adjacent carbon atoms together signify methylenedioxy, R 2 denotes H, CF 3 , F, Cl or C 1-5 alkoxy, R 3 and R 4 independently denote C 1-5 alkyl, C 2-5 alkenyl or benzyl, or R 3 and R 4 together signify a C 4-7 alkylene chain or -(CH 2 ) 2 -Z-(CH 2 ) 2 - where Z is O or S or N-substituted by C 1-5 alkyl, and X denotes -CH 2 - or -CO-, with the proviso that (i) no more than 3 of R, R 1 and R 2 are other than H and no more than 2 of R, R 1 and R 2 are other than H on any one ring, and (ii) R 1 and R 2 on ring A are not both halo, and (iii) no two CF 3 groups are on adjacent carbon atoms, may be obtained by (a) cyclizing by heating to at least 100‹ C. a compound of Formula (II) where R 7 denotes C 1-5 alkyl, C 2-5 alkenyl or benzyl, to form a compound of Formula (I) in which X is -CO-, or (b) reducing using an alkali metal borohydride, in an inert organic solvent and at a temperature of - 20‹ to 80‹ C. and in the presence of boron trifluoride etherate a compound of Formula I where X is -CO- and treating the resulting adduct with concentrated acid at a temperature of from 40‹ C. to the reflux temperature of the reaction mixture to form a compound of Formula I in which X is -CH 2 -. Intermediates of Formula (II) may be obtained by condensing a compound of Formula (III) with a compound of Formula (IV) in an inert organic solvent. Pharmaceutical compositions useful as hypotensives or diuretics comprise a compound of Formula I together with a pharmaceutically acceptable carrier or diluent, preferably in forms suitable for oral administration.