Patent ID: 8748596

Claim:
A process for the preparation of a compound of formula (I-E) wherein R 1 is selected from the group consisting of C 1-4 alkyl and C 3-10 cycloalkyl; m is 2 R 2 is selected from the group consisting of —OCHR 3 R 4 and —Z—Ar; R 3 is hydrogen and R 4 is a C 3-10 cycloalkyl or heterocycloalkyl ring; wherein the C 3-10 cycloalkyl or the heterocycloalkyl ring is unsubstituted or substituted with —C 1-4 alkyl or acetyl; alternatively, R 3 and R 4 are taken together with the carbon to which they are attached to form a C 3-10 cycloalkyl or heterocycloalkyl ring; wherein the C 3-10 cycloalkyl or the heterocycloalkyl ring is unsubstituted or substituted with —C 1-4 alkyl or acetyl; Z is selected from the group consisting of S and O; Ar is a phenyl or heteroaryl; wherein the phenyl or heteroaryl is unsubstituted or substituted with one, two, or three R 5 substituents; wherein each R 5 substituent is independently selected from the group consisting of halogen, —C 1-4 alkyl, —OH, —OC 1-4 alkyl, —SC 1-4 alkyl, —CN, —CONR a R b , and —NO 2 ; and wherein R a and R b are each independently —H or —C 1-4 alkyl; or a pharmaceutically acceptable salt, a pharmaceutically acceptable prodrug, or a pharmaceutically active metabolite thereof; comprising reacting a compound of formula (V-S) with an aldehyde or ketone derivative of the desired R 1 substituent group; neat or in an organic solvent; to yield the corresponding compound of formula (IX); reacting the compound of formula (IX) with a compound of formula (VI), wherein LG 1 is a first leaving group and LG 2 is a leaving group; in the presence of a reducing agent; in an organic solvent; to yield the corresponding compound of formula (X-E) reacting the compound of formula (X-E) with a compound of formula (XII); in the presence of a first inorganic base; in an organic solvent; or reacting the compound of formula (X-E) with a compound of formula (XIII); in the presence of a second inorganic base; in an organic solvent; to yield the corresponding compound of formula (I-E).