Patent ID: 6313307
Filing Date: 2001-11-06
Classification: A61P,C07D

Abstract:
A process for the preparation of a compound of formula I: ##STR14##or a pharmaceutical acceptable salt thereof wherein:X is --NR.sub.1 --, --S(O).sub.g --, or --O--;R.sub.1 is --H, C.sub.1-6 alkyl, optionally substituted with one or more --OH, --CN or halo, --(CH.sub.2).sub.h -aryl, --COR.sub.1-1, --COOR.sub.1-2, --CO--(CH.sub.2).sub.h --COR.sub.1-1, --SO.sub.2 -C.sub.1-6 alkyl, --SO.sub.2 CH.sub.2 -aryl, or --(CO).sub.i -Het;R.sub.1-1 is --H, C.sub.1-6 alkyl, optionally substituted with one or more --OH, --CN or halo, --(CH.sub.2).sub.h -aryl, or --(CH.sub.2).sub.h --OR.sub.1-3 ;R.sub.1-2 is C.sub.1-6 alkyl, optionally substituted with one or more OH, CN or halo, --(CH.sub.2).sub.h -aryl, or --(CH.sub.2).sub.h --OR.sub.1-3 ;R.sub.1-3 is --H, C.sub.1-6 alkyl, --(CH.sub.2).sub.h -aryl, or --CO(C.sub.1-6 alkyl);R.sub.2 is --H, C.sub.1-6 alkyl, --(CH.sub.2).sub.h -aryl, or halo;R.sub.3 and R.sub.4 are independently --H or halo;R.sub.5 is --H, C.sub.1-12 alkyl, optionally substituted with one or more halo, C.sub.3-12 cycloalkyl, C.sub.1-6 alkoxy;aryl is a phenyl, pyridyl or naphthyl moiety, optionally substituted with one or more --F, --Cl, --Br, --I, --OH, --SH, C.sub.1-6 alkyl, or C.sub.1-6 alkoxy;Het is 5, 6, or 9 membered heterocyclic rings having one to three O, N and S atom;g is 0, 1 or 2; h is 1,2, 3 or 4; i is 0 or 1; m is 0, 1, or 2; n is 0, 1, or 2; the fotted line ------ is a single or double bond; and with the proviso that m and n taken together are 1, or 2; which comprises:a) introducing --C(.dbd.O)R.sub.5 or --C(.dbd.O)R.sub.5-1 into the amino group of a compound of the formula II; ##STR15##b) when X.sub.1 is a protected X in formula III, deprotecting the protecting group by catalytic hydrogenation of a compound of formula III; ##STR16##c) when ------ is a single bond, catalytically hydrogenating a compound of formula I;d) when ------ is a double bond, eliminating an element of water from a compound of formula IV; ##STR17##e) when X is NR.sub.1 and R.sub.1 is --COR.sub.1-1, --COOR.sub.1-2, --CO--(CH.sub.2).sub.h --COR.sub.1-1, --SO.sub.2 -C.sub.1-6 alkyl, --SO.sub.2 CH.sub.2 -aryl, or --(CO)-Het, reacting a compound of formula V ##STR18##with L--COR.sub.1-1, L--COOR.sub.1-2, L--CO--(CH.sub.2).sub.h --COR.sub.1-1, L--SO.sub.2 --C.sub.1-6 alkyl, L--SO.sub.2 CH.sub.2 -aryl, or L--(CO).sub.i -Het;wherein X.sub.1 is X or protected X; R.sub.5-1 is R.sub.5 or protected R.sub.5 ;R.sub.1, R.sub.1-1, R.sub.1-2, R.sub.2, R.sub.3, R.sub.4, R.sub.5, aryl, Het, X and ------ are as defined above, L is a leaving group; andf) thereafter, if necessary, removing any protecting groups.