Patent ID: 8536345

Claim:
A process for the preparation of a compound of formula I, or a tautomer, stereoisomer, optical isomer, prodrug, or pharmaceutically acceptable salt thereof: comprising (a) contacting a compound of formula II with a chiral base selected from the group consisting of: in the presence of a deprotonating reagent and alkylating agent R 3 -LG; wherein: Z is S or O; R 1 is selected from C 1-8 alkyl, C 2-8 alkenyl, C 3-10 -cycloalkyl, C 3-10 -cycloalkenyl, C 3-10 -cycloalkyl-C 1-8 -alkyl, C 3-10 -cycloalkenyl-C 1-8 -alkyl, aryl, aryl-C 1-8 -alkyl, heterocyclyl, heterocyclyl-C 1-8 -alkyl and haloalkyl; wherein any aryl, cycloalkyl, or heterocyclyl residue is optionally independently substituted by one or more C 1-8 -alkyl, aryl, halogen, halo-C 1 -C 8 -alkyl, HO—C 1 -C 8 -alkyl, R 4 R 5 N—C 1 -C 8 -alkyl, C 1 -C 8 -alkyl-OR 6 , —OR 6 , (C 3 -C 10 )-cycloalkyl or C 1 -C 8 -alkyl-sulfonyl; R 2 and R 3 are independently selected from C 1-8 -alkyl, C 1-8 -alkoxy, C 3-10 -cycloalkyl, heterocyclyl, C 3-10 -cycloalkyl-C 1-8 -alkyl, CN—C 1-8 -alkyl, aryl, aryl-C 1-8 -alkyl, heterocyclyl-C 1-8 -alkyl and haloalkyl; wherein any aryl, cycloalkyl, or heterocyclyl residue is optionally independently substituted by one or more C 1-8 -alkyl, aryl, halogen, halo-C 1 -C 8 -alkyl, HO—C 1 -C 8 -alkyl, R 4 R 5 N—C 1 -C 8 -alkyl, C 1 -C 8 -alkyl-OR 6 , —OR 6 , (C 3 -C 10 )-cycloalkyl or C 1 -C 8 -alkyl-sulfonyl; R 4 and R 5 are each independently selected from hydrogen, C 1 -C 8 alkyl, C 1 -C 8 alkoxy, —NR 6 R 6 , —S—(C 1 -C 8 )alkyl, aryl and heterocyclyl; where in the definition of R 4 and R 5 any alkyl, alkoxy, heterocyclyl or aryl may be substituted with one to three substituents selected from -halo, unsubstituted C 1 -C 8 alkyl, unsubstituted C 1 -C 8 alkoxy, unsubstituted C 1 -C 8 thioalkoxy and unsubstituted aryl(C 1 -C 4 )alkyl R 6 is independently selected from hydrogen, C 1 -C 8 alkyl, aryl-C 1 -C 8 alkyl, C 1 -C 8 alkoxy, —S—(C 1 -C 8 )alkyl, heterocyclyl and aryl; where in the definition of R 6 any alkyl, heterocyclyl or aryl may be substituted with one to three substituents selected from -halo, unsubstituted C 1 -C 8 alkyl, unsubstituted C 1 -C 8 alkoxy, unsubstituted C 1 -C 8 thioalkoxy and unsubstituted aryl(C 1 -C 4 )alkyl LG is a leaving group.