Synthetic process research of a novel IDO1 inhibitor HS-10319
The synthetic pathway of a novel IDO1 inhibitor HS-10319 was optimized in this study.Starting with malononitrile,4-amino-N'-hydroxy-1,2,5-oxadiazole-3-carbonyl chloride(4)was obtained through one-pot process and diazotization reaction.Using dimethyl disulfide as the starting material,a highly stereoselective S-configured methyl sulfoxide compound(7)was obtained through oxidation reaction and reaction with diaceton-D-glucose under basic condition.Intermediate 7 was substituted with intermediate 4 after substitution and amination,and then the target compound HS-10319 was obtained through rearrangement,diazotization,substitution,cyclization,condensation and hydrolysis.The structures of HS-10319 and the key intermediates were confirmed by 1H-NMR,13C-NMR and MS.The overall yield was 8.06％(based on malononitrile)with the purity of 98.9％(determined by HPLC).In addition,the corresponding process parameters were determined focusing on the quantity of reagents and the selection of crystallization systems.The improved process has the advantages of optimized process parameters set reasonably,excellent process stability,stable product quality and easy controllability,which is suitable for industrial-scale production and aligned with conventions prevalent in chemical literature.
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