PROCESS FOR PREPARING PURE CYCLOALKANOINDOLE- AND AZAINDOLE- AND PYRIMIDO/1,2a/INDOLECARBOXYLIC ACIDS AND THEIR ACTIVATED DERIVATIVES, INTERMEDIATES FOR THE PREPARATION THEREOF AND THEIR USE

Preparation of (heterocyclyl-methyl)phenylacetic acid compounds of formula (I) and its salts comprises (1) diastereoselective alkylation of a compound of formula CH3-Ar-CH2COOR6 (II) with a compound of formula T-Z (III) in an inert solvent in the presence of a base to give the compound of formula CH3-Ar-CHT(*)COOR6 (IV); (2) halogenation of (IV) to give the compound of formula R7-CH2-Ar-CHT(*)COOR6 (V); (3) reacting (V) with a compound A-H (VI) to give the compound of formula A-CH2-Ar-CHT(*)COOR6 (VII); and (4a) hydrolysis of (VII) to give (I; Q = OH), or (4b) reaction with the appropriate compound to give (I; Q = activated group). Ar = phenylene; A = a group of formula (a) or (b') (N.B., (b') is described as an aza-indole and given everywhere else as a group of formula (b); A', D, E, G, L, M = H or R; R1+R2 complete benzene, pyridine or a ring of formula (c) (all optionally substituted by mono- to tri-substituted by R); R5 = H or 1-4C alkyl; R3+R4 complete benzene, 4-8 membered cycloalkene or 4-8 membered oxocycloalkene group (all optionally mono- to tri-substituted by R); R = halo, CF3, CO2H, OH, 1-6C alkoxy, 1-6C alkoxycarbonyl or 1-6C alkyl (optionally substituted by OH or 1-4C alkoxy); T = 4-12C cycloalkyl or 1-12C alkyl; Q = OH or an activated group; OR6 = a chiral alcohol group; Z = a typical leaving group such as Br, Cl, I, mesyl, tosyl or SO2CF3, preferably I or Br; R7 = halo, such as Cl, Br or I, preferably Br. Also claimed is a method for preparing (I) by resolving (R,S) CH3-Ar-CH2COOH (X) by reaction with (R)- or (S)-phenylethylamine in an inert solvent followed by crystallisation of the resulting phenylethylammonium salt; reaction with isobutene in an inert solvent in the presence of an acid to give (XII) of formula (IV; R6 = tert. butyl); and treatment of (XII) as for (IV). The following compounds and their salts are new; (I; A = a group of formula (a1) or (b1); Q = OH or Cl); (IV; R6 = D- or L-menthyl or tert.-butyl and T is not isopropyl (sic)); (V; R6 = D- or L-menthyl or tert.-butyl R7 = Br)); and compounds described as (VII) with R6 = D- or L-menthyl and given the formula (A).