Patent ID: 6469166
Filing Date: 2002-10-22
Classification: A61P,C07D

Abstract:
A process for preparing a compound of the formula: including the stereoisomers and the pharmaceutically acceptable acid addition salt forms thereof, whereinX is S, SO or SO2; R1 is NR4R5 or OR5; R2 is C1-6alkyl, C1-6alkyloxy or C1-6alkylthio; R3 is hydrogen, C1-6alkyl, C1-6alkylsulfonyl, C1-6alkylsulfoxy or C1-6alkylthio; R4 is hydrogen, C1-6alkyl, mono- or di(C3-6cycloalkyl)methyl, C3-6cycloalkyl, C3-6alkenyl, hydroxyC1-6alkyl, C1-6alkylcarbonyloxyC1-6alkyl or C1-6alkyloxyC1-6alkyl; R5 is C1-8alkyl, mono- or di(C3-6cycloalkyl)methyl, Ar1CH2, C3-6alkenyl, C1-6alkyloxyC1-6alkyl, hydroxyC1-6alkyl, thienylmethyl, furanylmethyl, C1-6alkylthioC1-6alkyl, morpholinyl, mono- or di(C1-6alkyl)aminoC1-6alkyl, di(C1-6alkyl)amino, C1-6alkylcarbonylC1-6alkyl, C1-6alkyl substituted with imidazolyl; or a radical of formula -Alk-O-CO-Ar1; or R4 and R5 taken together with the nitrogen atom to which they are attached may form a pyrrolidinyl, piperidinyl, homopiperidinyl or morpholinyl group, optionally substituted with C1-6alkyl or C1-6alkyloxyC1-6alkyl; Ar is phenyl; phenyl substituted with 1, 2 or 3 substituents independently selected from halo, C1-6alkyl, trifluoromethyl, hydroxy, cyano, C1-6alkyloxy, benzyloxy, C1-6alkylthio, nitro, amino and mono- or di(C1-6alkyl)amino; pyridinyl; pyridinyl substituted with 1, 2 or 3 substituents independently selected from halo, C1-6alkyl, trifluoromethyl, hydroxy, cyano, C1-6alkyloxy, benzyloxy, C1-6alkylthio, nitro, amino, mono- or di(C1-6alkyl)amino and piperidinyl; and wherein said substituted phenyl may optionally be further substituted with one or more halogens; Ar1 is phenyl; phenyl substituted with 1, 2 or 3 subsitutuents each independently selected from halo, C1-6alkyl, C1-6alkyloxy, di(C1-6alkyl)aminoC1-6alkyltrifluoromethyl, and C1-6alkyl substituted with morpholinyl; or pyridinyl; Alk is C1-6alkanediyl; which process comprises: a) alkylating a thiazolopyrimidine of formula (II) with an intermediate of formula (III) under conditions effective to alkylate said thiazolopyrimidine to form a compound of Formula I: b) O-alkylating a compound of formula (IX) with a compound of formula (X) in the presence of a suitable base under conditions effective to form a compound of formula (I-a), wherein R1 is OR5, â€ƒwherein in the above reaction schemes the radicals R1, R2, R3, R5 and Ar are as defined and W is a leaving group; and optionally converting the compounds of formula (I), into an acid addition salt by treatment with an acid, or conversely, converting the acid addition salt form into the free base by treatment with alkali; and, optionally preparing stereochemically isomeric forms thereof.