S(-)-CELIPROLOL, PHARMACEUTICALLY ACCEPTABLE SALTS, PREPARATION AND PHARMACEUTICAL COMPOSITIONS

摘要

1. Claims (for the Contracting States : BE, CH, DE, FR, GB, IT, LI, LU, NL, SE) S(-)-3-[3-acetyl-4-(3-tert.butylamino-2-hydroxypropoxy) phenyl]-1,1-diethylurea (S(-)-celiprolol) and its pharmaceutically acceptable acid addition salts. 1. Claims (for the Contracting State AT) Process for the preparation of S(-)-3-[3-acetyl-4-(3-tert.butylamino-2-hydroxypropoxy) phenyl]-1,1-diethylurea (S(-)-celiprolol) and its pharmaceutically acceptable acid addition salts, characterised in that a) the racemate of the formula see diagramm : EP0155518,P10,F1 in the form of the base is reacted with an enantiomer of a chiral resolving acid in a suitable organic solvent, the mixture of the two diastereomeric salts formed in this manner is separated by fractional crystallisation, and, after separating each diastereomeric salt which contains the laevorotatory enantiomer of the compound of the formula I in the S configuration, is reconverted into the free base or a pharmaceutically acceptable addition salt and the resolving acid is recovered, or b) S(+)-3-[3-acetyl-4-(2,3-epoxypropoxy)-phenyl]- 1,1-diethylurea of the formula see diagramm : EP0155518,P10,F2 is reacted with tertiary butylamine in the presence of water at room temperature or with gentle heating to a maximum of 40 degrees C, and then the laevorotatory enantiomer of the compound of the formula I thus obtained is converted as required into a pharmaceutically acceptable addition salt.