Process for the preparation of 11-amino-3-chloro-6,11-dihydro-5,5-dioxo-6-methyl-dibenzo[c,f][1,2]thiazepine and application to the synthesis of tianeptine

Abstract

Process for the industrial synthesis of the compound of formula (I): and its addition salts. Application to the synthesis of tianeptine and its pharmaceutically acceptable salts.

Description

[0001] The present invention relates to a new process for the industrial synthesis of 11-amino-3-chloro-6,11-dihydro-5,5-dioxo-6-methyl-dibenzo[c,-f][1,2]thiazepine of formula (I): 2[0002] and its addition salts.[0003] The compound of formula (I) is an important intermediate in the synthesis of tianeptine of formula (II): 3[0004] and its pharmaceutically acceptable salts.[0005] The compound of formula (II) and its addition salts have valuable pharmacological properties. They are stimulants of serotonin uptake, which makes them useful in the treatment of depression and anxiety.[0006] The compound of formula (II), its preparation and its use in therapeutics have been described in Patent Specification FR 2 104 728.[0007] In view of its pharmaceutical value, it was important to be able to produce the compound in an optimum yield and purity, using available, unproblematic starting materials and using a synthesis process that could be readily converted to the industrial scale.DESCRIPTION ...

AI Technical Summary

Problems solved by technology

That process does not, however, enable the compound of formula (II) to be obtained in a satisfactory yield and purity, in particular because of the instability of the ethyl 7-amino-heptanoate in the reaction mixture.

On an industrial scale, however, the treatment of such reaction mixtures is laborious, in particular requiring the evaporation of large amounts of methanol.

The preparation of primary amines by reacting halogenated compounds with ammonia generally yields rather unsatisfactory results: the yields are low and large proportions of secondary products (secondary and tertiary amines) are formed.

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