WERKWIJZE VOOR DE BEREIDING VAN EEN FARMACEUTISCH PREPARAAT MET HART-SELECTIEVE BETA -RECEPTOR BLOKKERENDE WERKING, GEVORMD PREPARAAT, VERKREGEN VOLGENS DEZE WERKWIJZE, ALS- MEDE WERKWIJZE VOOR HET BEREIDEN VAN NIEUWE 1-ALKYLAMINO-3-(GESUBSTITUEERD FENOXY)-PROPANOL-2-VERBIN- DINGEN EN ZUURADDITIEZOUTEN DAARVAN MET BETA -RECEPTOR BLOKKERENDE WERKING.

摘要

1308106 Substituted phenoxy-hydroxy propylamines HASSLE AB 19 April 1971 [18 Feb 1970] 21994/71 Heading C2C Novel compounds of the Formula IV wherein R1 is isopropyl or t-butyl, A is a straight or branched C 1-4 alkylene chain and Z is -OR2, -SO 2 R2, -SOR2, -SR2, NR 3 -COR2, NR 3 SO 2 R2 or NR3COOR2 wherein R2 is straight or branched C 1-3 alkyl and R3 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 R1NHCONHR1 or R1NH 2 ; (ii) reductively alkylating IV wherein R1 is H with acetone to produce IV, R1 = iPr; (iii) alkylating IV R1 = H with Hal-CH(CH 3 ) 2 where Hal is a halogen atom; (iv) hydrolysing a compound wherein R4 is a hydrolytioally removable group; (v) hydrolysing a compound with strong acid or strong alkali (vi) hydrolysing or pyrolysing a compound wherein R6 and R6 are hydrogen, C 1-4 alkyl, aralkyl or aryl; (vii) hydrolysing or hydrogenolysing a compound wherein R7 is an amine protecting group; (viii) reacting XCH 2 NHR1 or XCH 2 NR1R7 with a phenolate (ix) reducing a compound wherein B is -CHOHCO- or -COOH 2 -, (x) hydrolysing a compound wherein R8 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.