Patent ID: 6653475
Filing Date: 2003-11-25
Classification: A61P,C07D

Abstract:
A process for the preparation of pyrimidone derivatives of general formula I, wherein:Ar represents phenyl or phenyl substituted with one or more halogen and/or trifluoromethyl groups; R1 is C1-C4 alkyl; R2 represents hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, or cyclopropyl; A represents a benzene ring or a 5- or 6-memberd heterocyclic ring wherein one or more of the ring atoms are selected from the group consisting of N, O and S, which benzene or heterocyclic ring optionally can be fused to a benzene ring or a 5- or 6-membered heterocyclic ring containing one or more heteroatoms selected from N, O and S, and wherein A can be unsubstituted or have 1, 2, 3 or 4 substituents W on any of the rings; a group W represents C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, halogen, nitro, cyano, hydroxy, benzyloxy, hydroxymethyl, â€”NR3R4, â€”CONR3R4, â€”CH2â€”OCOâ€”R3, â€”COâ€”R3, â€”COOâ€”R3, â€”SOzR5, â€”C(&boxH;NR3) NHR6, â€”C(&boxH;NR6) OR3, and additionally one of the groups W can also represent 1-pyrrolyl, 1-imidazolyl, 1H-1,2,4-triazol-1-yl, 5-tetrazolyl (optionally substituted with C1-C4 alkyl), 1-pyrrolidinyl, 4-morpholinyl, 4-morpholinyl-N-oxide, a group â€”Xâ€”R7, or a group of formula (i)-(iv): R3 represents hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl or arylC1-C4 alkyl, wherein aryl represents phenyl or phenyl substituted with one or more C1-C4 alkyl, halogen, C1-C4 haloalkyl, C1-C4 alkoxy or C1-C4 haloalkoxy groups; R4 represents hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl, â€”COR3 or â€”COCF3; R5 represents C1-C4 alkyl; z represents 0, 1 or 2; R6 represents hydrogen, â€”CONH2, â€”COCH3, â€”CN, â€”SO2NHR3, â€”SO2R3, â€”OR3, â€”OCOR3 or â€”(C1-4 alkyl)â€”NH2; X represents a single bond, â€”Oâ€”, â€”SOzâ€”, â€”NR3â€”, or â€”C(&boxH;O)â€”; R7 represents a phenyl group optionally substituted with one or more groups R8; R8 represents C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, halogen, nitro, cyano, â€”NR3R4, â€”CONR3R4, â€”CH2â€”OCOâ€”R3, â€”COâ€”R3, â€”COOâ€”R3, â€”SOzR5, â€”C(&boxH;NR3)NHR6, â€”C(&boxH;NR6)OR3, a group of formula (iv) or R8 represents a phenyl group (optionally substituted with a C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, halogen, nitro or cyano group); R9 represents hydrogen or methyl; R10 represents hydrogen, isopropyl, cyclopentyl, cyclopropyl, 2-butyl, 3-pentyl, 3-hydroxy-2-butyl, or 2-hydroxy-3-pentyl; m represents 0 or 1; R11 represents halogen, C1-C4 haloalkyl, C1-C4 haloalkoxy, nitro, amino, cyano, or a group of formula (i); Y represents â€”CH2â€” or â€”C(&boxH;O)â€”; and Z represents NH or O; which comprises reacting a compound of formula II wherein R1 and Ar have the meaning defined above in relation to formula I, with a compound of formula III wherein A and R2 have the meaning defined above in relation to formula I, in the presence of a base.