Quinolidine derivatives

Claim 1

A process for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein: X is NH; or O when Ar is of formula (a) and R 2 is hydrogen or when Ar is a group of formula (b); R, is hydrogen, C 1-6 alkyl, phenyl or phenyl-C 1-6 alkyl, which phenyl moieties may be substituted by C 1 - 6 alkyl, C 1-6 alkoxy or halogen; Ar is a group of formula (a): wherein either R 2 is C 1-6 alkoxy and one of R 3 , R 4 and R s is hydrogen and the other two are selected from hydrogen, halogen, CF 3 , C 1-6 alkoxy, C 1-6 alkyl, C 1-6 -alkylthio, C 1-7 acyl, C 1-10 carboxylic acylamino, C 1 - 6 -alkyl S(O)n wherein n is O, 1 or 2, nitro or amino, aminocarbonyl or aminosulphonyl optionally substituted by one or two groups selected from C 1-6 alkyl, C 3-8 cycloalkyl, C 3-8 cycloalkyl C 1-4 alkyl or phenyl C 1-4 alkyl groups any of which phenyl moieties may be substituted by one or two groups selected from halogen, CF 3 , C 1-6 alkyl or C 1-6 alkoxy; or R 2 is hydrogen and R 3 , R 4 and R s are independently selected from hydrogen, C 1 - 6 alkyl, hydroxy, C 1-6 alkoxy, C 1-6 alkylthio or halo; or any two on adjacent carbon atoms together are C 1-2 alkylenedioxy and the third is hydrogen, C 1-6 alkyl, C 1-6 alkoxy or halo; or Ar is a group of formula (b); wherein Z is CH 2 , 0, S or NR 7 wherein R7 is hydrogen, C 1-6 alkyl, C 3 . 7 alkenyl-methyl, phenyl or phenyl C 1 . 4 alkyl either of which phenyl moieties may be substituted by one or two of halogen, CF 3 , C 1-6 alkoxy or C 1 . 6 alkyl; and Y is CH or N; or Z is CH or N and Y is NR a or CHR a where R a is as defined for R 7 above; R b is present when the COX linkage is attached at the phenyl ring, and is selected from hydrogen, halogen, CF 3 , hydroxy, C 1-6 alkoxy or C 1-6 alkyl; R 6 is hydrogen, halogen, CF,, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-7 acyl, C 1-7 acylamino, C 1 - 6 alkylsulphonylamino, N-( C 1-6 alkylsulphonyl)-N-C 1-4 alkylamino, C 1-6 alkylsulphinyl, hydroxy, nitro or amino, aminocarbonyl, aminosulphonyl, aminosulphonylamino or N-(aminosulphonyl)-C 1-4 alkylamino optionally N-substituted by one or two groups selected from C 1-6 alkyl, C 3-8 cycloalkyl, C 3-8 cycloalkyl C 1-4 alkyl, phenyl or phenyl C 1-4 alkyl groups or optionally N-disubstituted by C 4-5 polymethylene which process comprises reacting a compound of formula (V): Ar G (V) with a compound of formula (VI): wherein G is COQ were Q is a leaving group and L is NH2 or OH or a reactive derivative thereof and the remaining variables are as defined; and thereafter optionally converting any R 2 , R 3 , R 4 , R s , R 6 and R a and R b group to another R 2 , R 3 , R 4 , R s , R., R a and R b group respectively, and optionally forming a pharmaceutically acceptable salt of the resultant compound of formula (I).