Patent ID: 6521629
Filing Date: 2003-02-18
Classification: A61P,C07D

Abstract:
A process for the production of a compound of formula I, whereinR1 represents C1-4 alkoxy optionally substituted by one or more fluorine atoms; R2 represents H or C1-6 alkoxy optionally substituted by one or more fluorine atoms; R3 represents a 5- or 6-membered heterocyclic ring containing at least one heteroatom selected from N, O and S, the ring being optionally substituted by one or more groups selected from halogen C1-4 alkoxy, C1-4 alkyl and CF3; R4 represents a 4-, 5-, 6-, or 7-membered heterocyclic ring containing at least one heteroatom selected from N, O and S, the ring being optionally fused to a benzene ring or a 5- or 6-membered heterocyclic ring containing at least one heteroatom selected from N, O and S, the ring system as a whole being optionally substituted by one or more groups independently selected from OH, C1-4 alkyl, C1-4 alkoxy, halogen, CONR8R9, SO2NR8R9, (CH2)bNR8R9 and NHSO2(C1-4 alkyl), and when S is a member of the ring system, it may be substituted by one or two oxygen atoms; R8 and R9 independently represent H or C1-4 alkyl, together with the N atom to which they are attached they may represent a 5- or 6-membered heterocyclic ring containing at least one heteroatom selected from N, O and S; b represents 0, 1, 2 or 3; X represents CH or N; and L is absent; â€ƒor represents a cyclic group of formula Ia, â€ƒin which N is attached to the 2-position of the quinoline or quinazoline ring; A is absent or represents CO or SO2; Z represents CH or N; m represents 1 or 2, and in addition, when Z represents CH, it may represent 0; and n represents 1, 2 or 3, provided that the sum of m and n is 2, 3, 4 or 5; or represents a chain of formula Ib, â€ƒin which N is attached to the 2-position of the quinoline or quinazoline ring; Aâ€² and zâ€² have the same significance as A and Z above, respectively; R6 and R7 independently represent H or C1-4 alkyl; and p represents 1, 2 or 3, and in addition, when Zâ€² represents CH, it may represent 0; or a pharmaceutically acceptable salt thereof,wherein L is absent, X is N, and R4 comprises a nucleophilic nitrogen atom in the heterocyclic ring attached to the quinazoline ring, the process comprising reacting a compound of formula XXII with a compound of formula XXIXHâ€”R4aâ€ƒâ€ƒXXIX wherein R1, R2, R3, are as defined above, and R4a represents the groups defined by R4 which contain a nucleophilic nitrogen atom in the ring, this nucleophilic nitrogen atom being attached to H of Hâ€”R4a.