GB1308106A — Phenoxyhydroxypropylamines and their preparation

USPTO Abstract

1308106 Substituted phenoxy-hydroxy propylamines HASSLE AB 19 April 1971 [18 Feb 1970] 21994/71 Heading C2C Novel compounds of the Formula IV wherein R<SP>1</SP> is isopropyl or t-butyl, A is a straight or branched C 1-4 alkylene chain and Z is -OR<SP>2</SP>, -SO 2 R<SP>2</SP>, -SOR<SP>2</SP>, -SR<SP>2</SP>, NR 3 -COR<SP>2</SP>, NR 3 SO 2 R<SP>2</SP> or NR<SP>3</SP>COOR<SP>2</SP> wherein R<SP>2</SP> is straight or branched C 1-3 alkyl and R<SP>3</SP> is hydrogen or a straight or branched alkyl radioal and pharmaceutically acceptable acid addition salts thereof may be prepared by (i) reacting a compound V wherein X is an unsubstituted ethylene oxide ring or -CHOHCH 2 -halogen with a compound R<SP>1</SP>NHCONHR<SP>1</SP> or R<SP>1</SP>NH 2 ; (ii) reductively alkylating IV wherein R<SP>1</SP> is H with acetone to produce IV, R<SP>1</SP> = iPr; (iii) alkylating IV R<SP>1</SP> = H with Hal-CH(CH 3 ) 2 where Hal is a halogen atom; (iv) hydrolysing a compound wherein R<SP>4</SP> is a hydrolytioally removable group; (v) hydrolysing a compound with strong acid or strong alkali (vi) hydrolysing or pyrolysing a compound wherein R<SP>6</SP> and R<SP>6</SP> are hydrogen, C 1-4 alkyl, aralkyl or aryl; (vii) hydrolysing or hydrogenolysing a compound wherein R<SP>7</SP> is an amine protecting group; (viii) reacting XCH 2 NHR<SP>1</SP> or XCH 2 NR<SP>1</SP>R<SP>7</SP> with a phenolate (ix) reducing a compound wherein B is -CHOHCO- or -COOH 2 -, (x) hydrolysing a compound wherein R<SP>8</SP> is C 1-4 alkyl, aralkyl or aryl or, (xi) hydrogenolysing a compound wherein Y means the benzene ring is substituted with 1 to 4 halogen atoms. The intermediates V may be prepared by reacting an appropriately para-substituted phenol with chlorohydrin followed in the case where X is CHOHCH 2 Cl, by treatment with hydrochloric acid. 2 - Hydroxy - 3 - [p - (methoxyethyl) - phenoxy]- N - isopropyl propionamide may be prepared by reacting the free acid with isopropylamine, the free acid in turn being prepared by condensingp-methoxy ethyl phenol with 2-hydroxy- 3-chloropropionic acid. A 1 - isopropylamino - 3 - [bromo - p - (#- methoxyethyl) - phenoxy] - propanol - 2 may be prepared by brominating p-(#-methoxyethyl)- phenyl to give a brcmo-p-(#-methoxyethyl)- phenol which is reacted with chlorohydrin followed by isopropylamine to yield the required compound. Pharmaceutical compositions of the compounds IV may be used for treatment of heart diseases and vascular diseases when administered orally, parenterally or rectally with excipients or diluents.