Process for the stereoselective preparation of bicyclic heterocycles

A process for the stereoselective preparation of compounds of formula (I)

• optionally in the form of the tautomers thereof, and optionally the pharmacologically acceptable acid addition salts thereof,
• wherein
• R1 denotes a group selected from among 3-chloro-2-fluoro-phenyl-amino, 3-chloro-4-fluoro-phenylamino, 2-fluoro-3-methyl-phenylamino, 2,5-difluoro-3-methyl-phenylamino, 3-chloro-2-methyl-phenylamino- and 2-fluoro-5-methyl-phenylamino,
• characterised in that the process comprises reaction steps (1a) to (1d), wherein (1a) is the reaction of a compound of formula (II)
• with a compound of formula (III)
• to form a compound of formula (IV)
• (1b) is the cleaving of the benzyl group of the compound of formula (IV) in the presence of a catalyst to form a compound of formula (V)
• (1c) is the reaction of the compound of formula (V) with a chlorinating agent to form the hydrochloride of a compound of formula (VI)
• and
• (1d) is the reaction of the compound of formula (VI) with one of the compounds (i) to (vi) to form a compound of formula (I),
• wherein
• (i) is 3-chloro-2-fluoro-aniline,
• (ii) is 3-chloro-4-fluoro-aniline,
• (ii) is 2-fluoro-3-methyl-aniline,
• (iii) is 2,5-difluoro-3-methyl-aniline,
• (iv) is 3-chloro-2-methyl-aniline, and
• (vi) is 2-fluoro-5-methyl-aniline,
• while steps (1a) to (1d) take place successively in the order specified, or
• characterised in that the process comprises reaction steps (2a), (1c) and (1d) wherein (2a) is the reaction of a compound of formula (II)
• with a compound of formula (VII)
• to form a compound of formula (V)
• while the steps take place successively in the order specified.