Patent ID: 6265614
Filing Date: 2001-07-24
Classification: C07B,C07C,Y02P

Abstract:
A process for making an optically active R-enantiomer compound having the formula: ##STR59##wherein B is --CH.dbd.CH.sub.2, --CH.sub.2 OH, or --CH.sub.2 OR.sup.P, and R.sup.P is an alcohol protecting group;a is 1, 2, or 3;Q is R.sup.5 -phenyl, R.sup.5 -naphthyl, or R.sup.5 -heteroaryl;R.sup.5 represents 1-3 substituents independently selected from the group consisting of H, halogeno, --OR.sup.6, --OC(O)R.sup.6, --OC(O)N(R.sup.6) (R.sup.7), --N(R.sup.6)(R.sup.7), C.sub.1-6 alkyl, --CF.sub.3, --C.sub.2 F.sub.5, --COR.sup.6, --CO.sub.2 R.sup.6, --CON(R.sup.6)(R.sup.7), --S(O).sub.e R.sup.13, --CN, --OCF.sub.3, --NR.sup.6 CO.sub.2 R.sup.16, --NR.sup.6 COR.sup.7, --NR.sup.8 CON(R.sup.6)(R.sup.7), R.sup.15 -phenyl, R.sup.15 -benzyl, NO.sub.2, --N(R.sup.6)S(O).sub.2 R.sup.13 or --S(O).sub.2 N(R.sup.6)(R.sup.7); or adjacent R.sup.5 substituents can form an --O--CH.sub.2 --O-- group;R.sup.6, R.sup.7, R.sup.8, and R.sup.13 are independently selected from the group consisting of H, C.sub.1-6 alkyl, C.sub.2 -C.sub.6 hydroxyalkyl, C.sub.1 -C.sub.6 alkoxy-C.sub.1 -C.sub.6 alkyl, R.sup.15 -phenyl, and R.sup.15 -benzyl; or R.sup.6 and R.sup.7, together with the nitrogen to which they are attached, form a ring of 5 to 6 members, wherein 0, 1 or 2 ring members are selected from the group consisting of --O--, --S-- and --N(R.sup.19)--;R.sup.15 is 1 to 3 substituents independently selected from the group consisting of H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkylthio, halogeno, --CF.sub.3, --C.sub.2 F.sub.5, --COR.sup.10, --CO.sub.2 R.sup.10, --C(O)N(R.sup.10).sub.2, --S(O).sub.e R.sup.10a, --CN, --N(R.sup.10)COR.sup.10, --N(R.sup.10)CON(R.sup.10).sub.2 and --NO.sub.2 ;R.sup.16 is C.sub.1-6 alkyl, R.sup.15 -phenyl or R.sup.15 -benzyl;R.sup.10 and R.sup.10a are independently selected from the group consisting of H and C.sub.1-6 alkyl;R.sup.19 is H, C.sub.1 -C.sub.6 alkyl, --C(O)N(R.sup.10).sub.2, --CO.sub.2 R.sup.10, --(C(R.sup.8)(R.sup.9)).sub.f --CO.sub.2 R.sup.10 or --(C(R.sup.8)(R.sup.9)).sub.u --C(O)N(R.sup.10).sub.2 ;R.sup.9 is selected from the group consisting of R.sup.6 and --OR.sup.6 ;e is 0, 1 or 2, provided that when e is 1 or 2, R.sup.13 and R.sup.10a are not H;f is an integer from 1 to 6;u is an integer from 0 to 6;R.sup.a and R.sup.c are the same, and are H, or are selected from alkyl, cycloalkyl and aryl groups, said groups being optionally substituted with one or more substituents selected from alkyl, cycloalkyl, aryl, or --OH; or R.sup.a and R.sup.c together with the C--N--C chain to which they are bound, form a 5-7 membered ring;R.sup.b and R.sup.d are the same, and are H, or are selected from alkyl, cycloalkyl and aryl groups, said groups being optionally substituted with one or more substituents selected from alkyl, cycloalkyl, aryl, or --OH; andD is a directing group capable of directing lithiation alpha to a nitrogen atom of a nitrogen compound having D as a substituent bound to the nitrogen atom when said nitrogen compound is reacted with s-butyl lithium, said nitrogen compound having the formula ##STR60##wherein R.sup.a, R.sup.b, R.sup.c, and R.sup.d are as defined above;said process comprising reacting a compound having the formula ##STR61##wherein R.sup.a, R.sup.b, R.sup.c, and R.sup.d are as defined above, with a compound having the formula ##STR62##wherein B, a, R.sup.a, R.sup.b and Q are as defined above, and R.sup.e and R.sup.f are independently selected from the group consisting of alkyl, alkoxy, cycloalkyl and aryl groups, said groups being optionally substituted with one or more substituents selected from alkyl, alkoxy, cycloalkyl, aryl, NH.sub.2, or --OH, or R.sup.e and R.sup.f together with the nitrogen atom to which they are bound, form a 5-7 membered ring.