Patent ID: 8034932
Filing Date: 2011-10-11
Classification: A61P,C07D

Abstract:
1. A process for the manufacture of a compound of formula I or a pharmaceutically acceptable salt thereof, which comprises reacting a compound of formula II, wherein L is a leaving group and X is a group Z which is N-(methyl)methylsulfonylamino (CH 3 SO 2 N(CH 3 )—); with a compound of the formula III, wherein A is selected from a group (i) to (vii) below, wherein P 1 and P 2 are independently selected from hydrogen and a hydroxy protecting group, or P P P P P P P and unless otherwise stated R 1 , R 2 , R 3 and R 4 are independently carboxy protecting groups; in the presence of a catalytically effective amount of a palladium catalyst and in the presence of a base; followed by (a) when A is a group (i), carrying out in any order the steps of (1) when P 1 is a hydroxy protecting group, removal of the protecting group P 1 ; (2) when P 2 is a hydroxy protecting group, removal of the protecting group P 2 ; and (3) removal of the protecting group R 1 ; (b) when A is a group (ii), carrying out in any order the steps of (1) asymmetric reduction of the carbonyl group adjacent to the carbon-carbon double bond; (2) when P 3 is a hydroxy protecting group, removal of the protecting group P 3 ; and (3) removal of the protecting group R 2 ; (c) when A is a group (iii), carrying out in any order the steps of (1) when P 4 is a hydroxy protecting group, removal of the protecting group P 4 ; (2) when P 5 is a hydroxy protecting group, removal of the protecting group P 5 ; (3) removal of the protecting group P 6 ; and (4) removal of the protecting group P 7 ; (d) when A is a group (iv), carrying out in any order the steps of (1) when P 8 is a hydroxy protecting group, removal of the protecting group P 8 ; (2) asymmetric hydration of the carbon-carbon double bond adjacent to the ester group COOR 3 ; and (3) removal of the protecting group R 3 ; (e) when A is a group (v), carrying out in any order the steps of (1) when P 9 is a hydroxy protecting group, removal of the protecting group P 9 ; and (2) hydrolysis under basic conditions; (f) when A is a group (vi), carrying out in any order the steps of (1) asymmetric hydration of the ring carbon-carbon double bond; and (2) hydrolysis under basic conditions; and (g) when A is a group (vii), carrying out in any order the steps of (1) asymmetric reduction of the carbon-carbon double bond adjacent to the group COOR 4 ; (2) when P 10 is a hydroxy protecting group, removal of the protecting group P 10 ; (3) when P 11 is a hydroxy protecting group, removal of the protecting group P 11 ; and (4) removal of the protecting group R 4 ; whereafter, when the product is obtained in the free acid form, optionally forming a pharmaceutically acceptable salt of the compound of formula I, or when the product is obtained as a salt, optionally converting the product to a different pharmaceutically acceptable salt.