PROCESS FOR PREPARATION OF TENELIGLIPTIN Russian patent published in 2018 - IPC C07D417/14 A61K31/401 A61K31/427 A61K31/496 

FIELD: chemistry.

SUBSTANCE: invention relates to a process for the preparation of teneligliptin, a compound of formula I, or a salt thereof, or a hydrate thereof. Process comprises a) reacting a compound of formula 11 with bis-(2-chloroethyl)amine, or an N-protected derivative thereof, or a salt thereof, to obtain a compound of formula Int-B, or an N-protected derivative thereof, or a salt thereof or a) reacting 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde, a compound of formula 30, with piperazine-1-carboxylic acid tert-butyl ester to obtain tert-butyl-4-(4-formyl-3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazine-1-carboxylate, a compound of formula 31, which is then deprotected to obtain a compound of formula Int-B; b) reacting a compound of formula Int-B, or an N-protected derivative thereof, or a salt thereof with a compound of formula 13 to obtain a compound of formula 14 wherein R is an amino protecting group selected from the group consisting of aralkyl, acyl, lower alkoxycarbonyl, aralkyloxycarbonyl, lower alkanesulfonyl, arylsulfonyl, tri- (lower alkyl) silyl, triphosgene; and c) deprotecting the compound of formula 14 to produce teneligliptin, a compound of formula I, or a salt thereof or a hydrate thereof. Invention also relates to a process for the preparation of teneligliptin 2,5 hydrobromide hydrate, which comprises the crystallisation of teneligliptin 2,5 hydrobromide or a hydrate thereof from a solvent selected from the group consisting of methanol, n-butanol, t-butanol, dimethylacetamide, dimethylformamide, tetrahydrofuran, and mixtures thereof.

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EFFECT: processes according to the invention enables to obtain teneligliptin or its salts with high yields and purity.

8 cl, 5 dwg, 18 ex