Patent ID: 6107508
Filing Date: 2000-08-22
Classification: C07C,C07D

Abstract:
A process for the preparation of a compound of formula (I): ##STR44## or a pharmaceutically acceptable salt form thereof; wherein:r is an integer from 0 to 4;R.sup.1 is independently selected at each occurrence from the group consisting of:H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.10 alkenyl, C.sub.2 -C.sub.10 alkynyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.4 -C.sub.12 cycloalkylalkyl, --NR.sup.1c R.sup.1d, --OR.sup.1e and --SR.sup.1e ;R.sup.1c and R.sup.1d are independently selected at each occurrence from the group consisting of:H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.10 alkenyl, C.sub.2 -C.sub.10 alkynyl, C.sub.3 -C.sub.6 cycloalkyl and C.sub.4 -C.sub.12 cycloalkylalkyl;alternatively, R.sup.1c and R.sup.1d are taken together to form a heterocyclic ring selected from the group consisting of:piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine and thiomorpholine, each heterocyclic ring optionally substituted with 1-3 C.sub.1 -C.sub.4 alkyl groups;R.sup.1e is independently selected at each occurrence from the group consisting of:H, C.sub.1 -C.sub.10 alkyl, C.sub.3 -C.sub.6 cycloalkyl, and C.sub.4 -C.sub.6 cycloalkylalkyl;R.sup.2 is selected from the group consisting of:H, C.sub.2 -C.sub.4 alkenyl, C.sub.2 -C.sub.4 alkynyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.4 -C.sub.10 cycloalkylalkyl, C.sub.1 -C.sub.4 hydroxyalkyl, C.sub.1 -C.sub.4 haloalkyl, and C.sub.1 -C.sub.4 alkyl substituted with 0-5 R.sup.2a ;R.sup.2a is independently selected at each occurrence from the group consisting of:H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.10 alkenyl, C.sub.2 -C.sub.10 alkynyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.4 -C.sub.12 cycloalkylalkyl, halo, CN, C.sub.1 -C.sub.4 haloalkyl, --OR.sup.2e, and --SR.sup.2e ; andR.sup.2e is independently selected at each occurrence from the group consisting of:H, C.sub.1 -C.sub.10 alkyl, C.sub.3 -C.sub.6 cycloalkyl, and C.sub.4 -C.sub.6 cycloalkylalkyl;the process comprising the steps of:(1) contacting the compound of formula (II): ##STR45## with a halogenating agent to form a compound of formula (III): ##STR46## wherein X is a halogen derived form the halogenating agent; (2) contacting the compound of formula (III) with a strong base followed by addition of an alkylborate to form a compound of formula (IV): ##STR47## (3) contacting the compound of formula (IV) with a compound of formula (V): ##STR48## wherein Y second halogen; in the presence of a catalyst and a weak base to form a compound of formula (VI): ##STR49## (4) contacting the compound of formula (VI) with an isomerization base to form a compound of formula (I), or a pharmaceutically acceptable salt form thereof.