IE35693B1 - 1-phenoxy-2-hydroxy-3-hydroxyalkylaminopropanes and processes for their preparation - Google Patents

Abstract

1364280 1-phenoxy, 2-hydroxy, 3-hydroxyalkylamino-propanes BOEHRINGER INGELHEIM GmbH 4 Oct 1971 [5 Oct 1970] 46103/71 Heading C2C [Also in Division A5] Novel compounds of general Formula I and their esters and acid addition salts, where R 1 represents cyano, ethynyl, propargyl, allyl, amino, hydroxymethyl methoxy, hydroxycarbonyl methoxycarbonyl or allyloxy; R 2 represents a hydrogen, chlorine, methyl or cyano; or R 1 and R 2 together represent a 3,4- methylene-dioxy group; R 3 represents hydrogen and R 4 represents a straight or branched hydroxyalkyl group with 3 to 6 C atoms (with the proviso that R 4 is not 1,1-dimethyl-2- hydroxyethyl or 1,2 - dimethyl - 2 - hydroxyethyl when R 1 is 4-amino) are prepared by (1) reacting a compound of Formula II where Z represents the group or -CH.OH-CH 2 -Halogen with an amine NH 2 -R 4 , (2) hydrolysing or hydrogenolysing a compound of Formula IV where G is an acyl or tetrahydropyranyl group, (3) reacting a compound of Formula V with a hydroxyalkyl (with 3 to 6 C atoms)- halide, -tosylate or -mesylate or with a hydroxyaldehyde or hydroxyketone of 3 to 6 C atoms under conditions of reductive alkylation with hydrogen, (4) hydrolysing or hydrogenolysing a compound of Formula VI where Sch is preferably a benzyl carbobenzoxy or acyl group, (5) hydrolysing a compound of Formula VII preferably by using a strong alkali in an aqueous or aqueous/alcoholic medium, (6) hydrolysing or pyrolysing a compound of Formula VIII where R 5 and R 6 are either a hydrogen atom or an alkyl, aralkyl or aryl group, (7) chlorinating a compound Ar-OCH 2 -CHOH-CH 2 -NHR 4 , where Ar represents a phenyl group substituted by R<SP>1</SP> and R 3 preferably by using hydrogen peroxide and a hydrohalic acid, (8) reducing a compound II in which Z is CO-CH 2 -NHR 4 or CHOH-CO-NHR 4 , (9) reacting by known methods a compound X in which A is halogen, aldehyde, amide, oxime, haloalkyl nitro or alkoxy carbonyl to form a compound I in which R 1 is cyano, amino hydroxymethyl, or hydroxycarbonyl, or (10) reacting by known methods a compound X1 in which B is aldehyde or amino to form a compound I in which R 2 is other than hydrogen. Compounds I may be formed as their optical isomers. Acetates and propionates of compounds I may be formed by conventional procedures. Compounds I show #-adrenolytic activity and blood-pressure decreasing properties and form with a carrier or excipient a pharmaceutical composition which may be administered orally rectally or parenterally. The compositions may include coronary dilators, sympathicominetics cardiac glycosides or tranquillizers and in particular 2,6-bis-(diethanolamino-)-4,8-dipiperidino-pyrimido [5,4-d]-pyrimidine. [GB1364280A]