METHOD OF PRODUCING 3,5-DIFLUOROBENZYLAMIDE (S)-3-HYDROXY-1-(1H-INDOL-5-YL)-2-OXO-PYRROLIDINE-3-CARBOXYLIC ACID Russian patent published in 2024 - IPC C07D403/10 C07D209/08 

FIELD: organic synthesis.

SUBSTANCE: invention relates to a method of the preparation of 3,5-difluoro-benzylamide (S)-3-hydroxy-1-(1H-indol-5-yl)-2-oxo-pyrrolidine-3-carboxylic acid (compound S-9), which is an inhibitor of MetAP-2. The method of preparing S-9 is characterized by the following: 2-oxo-1-(1-(phenylsulfonyl)-1H-indol-5-yl)pyrrolidine-3-carboxylic acid (compound 5) is reacted with 3,5-difluorobenzylamine with producing 1-[1-(benzenesulfonyl)-1H-indol-5-yl]-N-[(3,5-difluorophenyl)methyl]-2-oxopyrrolidine-3-carboxamide (compound 12). Then, in a key step, compound 12 is enantioselectively oxidized using the asymmetric oxidizing agent "Davis oxaziridine" to give (3S)-1-[1-(benzenesulfonyl)-1H-indol-5-yl]-N-[(3,5-difluorophenyl)methyl]-3-hydroxy-2-oxopyrrolidine-3-carboxamide (compound 13). The phenylsulfonyl group of compound 13 is then eliminated to give 3,5-difluorobenzylamide (S)-3-hydroxy-1-(1H-indol-5-yl)-2-oxo-pyrrolidine-3-carboxylic acidю

EFFECT: provision of a method of obtaining the target product with fewer synthesis steps.

8 cl, 12 ex