Patent ID: 6809200
Filing Date: 2004-10-26
Classification: C07D

Abstract:
A process for the preparation of a compound of general formula (I): or a pharmaceutically or veterinarily acceptable salt, polymorph and/or solvate thereof, whereinQ represents O or NR5 R1 represents H, lower alkyl, Het, alkylHet, aryl or alkylaryl (which latter five groups are all optionally substituted with one or more substituents selected from cyano, nitro, lower alkyl, OR6, OC(O)R7, C(O)R8, C(O)OR9, C(O)NR10R11, NR12R13 and SO2NR14R15) R2 represents H, cyano, nitro, OR6, OC(O)R7, C(O)R8, C(O)OR9, C(O)NR10R11, NR12R13, SO2NR14R15, lower alkyl, Het, alkylHet, aryl or alkylaryl (which latter live groups are all optionally substituted with one or more substituents selected from cyano, nitro, lower alkyl, OR6, OC(O)R7, C(O)R8, C(O)OR9, C(O)NR10R11, NR12R13 and SO2NR14R15) R3 represents H, lower alkyl, alkylHet or alkylaryl (which latter three groups are all optionally substituted with one or more substituents selected from cyano, nitro, lower alkyl, OR6, OC(O)R7, C(O)R8, C(O)OR9, C(O)NR10R11, NR12R13 and SO2NR14R15) R4 represents H, halo, cyano, nitro, OR6, C(O)R8, C(O)OR9, C(O)NR10R11, NR10R13, NR16Y(O)R17, N[Y(O)R17]2, S(O)R18, SO2R19, C(O)AZ, lower alkyl, lower alkenyl, lower alkynyl, Het, alkylHet, aryl, alkylaryl (which latter seven groups are all optionally substituted with one or more substituents selected from cyano, nitro, lower alkyl, OR6, OC(O)R7, C(O)R8, C(O)OR9, C(O)NR10R11, NR12R13 and SO2NR14R15) Y represents C or S(O) A represents lower alkylene Z represents OR6, Het or aryl (which latter two groups are both optionally substituted with one or more substituents selected from cyano, nitro, lower alkyl, OR6, OC(O)R7, C(O)R8, C(O)OR9, C(O)NR10R11, NR12R13 and SO2NR14R15) R10 and R11 independently represent H or lower alkyl (which latter group is optionally substituted with one or more substituents selected from cyano, nitro, lower alkyl, OR6, OC(O)R7, C(O)R8, C(O)OR9, C(O)NR10aR11a, NR12R13, SO2NR14R15 and NR20S(O)2R21 or Het or aryl optionally substituted with one or more of said latter thirteen groups) or one of R10 and R11 may be lower alkoxy, amino or Het, which latter two groups are both optionally substituted with lower alkyl R10a and R11a independently represent H or lower alkyl (which latter group is optionally substituted with one or more substituents selected from cyano, nitro, lower alkyl, OR6, OC(O)R7, C(O)R8, C(O)OR9, SO2NR14R15 and NR20 S(O)2R21 or Het or aryl optionally substituted with one or more of said latter thirteen groups) or one of R10a and R11a may be lower alkoxy, amino or Het, which latter two groups are both optionally substituted with lower alkyl R12 and R13 independently represent H or lower alkyl (which latter group is optionally substituted with one or more substituents selected from OR6, C(O)OR9, C(O)NR22R23 and NR24R25), one of R12 or R13 may be C(O)-lower alkyl or C(O)Het (in which Het is optionally substituted with lower alkyl), or R12 and R13 together represent C3-7 alkylene (which alkylene group is optionally unsaturated, optionally substituted by one or more lower alkyl groups and/or optionally interrupted by O or NR26) R14 and R15 independently represent H or lower alkyl or R14 and R15, together with the nitrogen atom to which they are bound, form a heterocyclic ring R16 and R17 independently represent H or lower alkyl (which latter group is optionally substituted with one or more substituents selected from OR6, C(O)OR9, C(O)NR22R23 and NR24R25) or one of R16 and R17 may be Het or aryl, which latter two groups are both optionally substituted with lower alkyl R5, R6, R7, R8, R9, R18, R19, R20, R22, R23, R24 and R25 independently represent H or lower alkyl R18 and R19 independently represent lower alkyl R21 represents lower alkyl or aryl R26 represents H, lower alkyl, aryl, C(O)R27 or S(O)2R28 R27 represents H, lower alkyl or aryl R28 represents lower alkyl or aryl Het represents a four- to twelve-membered heterocyclic group, optionally substituted by one or more substituents selected from cyano, nitro, oxo, lower alkyl, OR6, OC(O)R7, C(O)R8, C(O)OR9, and SO2NR14R15, which group contains one or more heteroatoms selected from nitrogen, oxygen, sulphur and mixtures thereof said process comprising reacting, in an inert, alcoholic, or mixed inert/alcohol solvent, a compound of formula (III), (IV) or (V) in the presence of âˆ’OR3 and a hydroxide trapping agent which is an ester of the formulaTOC(O)W wherein OT is OR3 or OT is the residue of non-nucleophilic alcohol or TOH is an alcohol which can be azeotropically removed during the reaction; and C(O)W is the residue of a carboxylic acid; or, alternatively, in the case of compounds of formulae (IV) or (V) reacting, in an inert, alcoholic, or mixed inert/alcohol solvent and in the presence of an auxiliary base and a hydroxide trapping agent which is an ester of the formula TOC(O)W as defined above wherein X is a leaving group and Q and R1 to R4 are as defined above, provided that in said process, Q is not NR5 when a compound of formula (III) or (IV) is used therein.