Study on synthetic process of a new JAK inhibitor HS-10360
As the oral small molecule targeted drugs with a novel mechanism,JAK inhibitors are widely used in tumors,ulcerative colitis and other fields.In this paper,a synthetic method for 1-｛(1R,3S,5S)-3-(｛ 4-[(5-methyl-1 H-pyrazol-3-yl)amino]thieno[2,3-d]pyrimidin-2-yl ｝ amino)-9-azabicyclo[3.3.1]non-9-yl}-2-(methylamino)ethan-1-one(HS-10360)as a second generation high potency JAK inhibitor was designed.As the raw material,2,4-dichlorothieno[2,3-d]pyrimidine was replaced with 3-amino-5-methyl-1H-pyrazole and exo-3-amino-9-Boc-9-azabicyclo[3.3.1]nonane respectively,and then condensed with Boc-sarcosine,deprotected and free to obtain HS-10360.This method has the advantages of short reaction route and mild reaction conditions,the overall yield was 21.5％and the purity of the final product was 99.8％.After key synthetic process optimization,pilot scale and cGMP scale production,it was confirmed that the synthetic process is stable,the quality of product is high,and it is suitable for industrial production.
JAK inhibitorCrohn diseasesynthetic processprocess optimizationindustrialization
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