Merck Sharp + Dohme Corp.

China Resources Saike Pharmaceutical Co., Ltd.

Deqian Bian

Lihu Yang

Joey Lee Methot

Jason David Katz

Yan Yang

Jianmin Fu

Meredeth Ann McGowan

Shimin Xu

Kin Chiu Fong

Kathryn Ann Lipford

Ning Fu

Yabin Li

Moyi Liu

Fangze Chi

Guoquan Xu

A resolution method of axial chiral enantiomers of lesinurad (2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid) adopts inexpensive and readily available quinoline natural products and derivatives thereof, such as quinine, cinchonine, quinidine or cinconidine as resolving agents to react with lesinurad racemate in an organic solvent to form a salt, and the salt is dissociated by acidification so as to obtain optically pure (R)- or (S)-2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid. The method can give axial chiral enantiomer of lesinurad in R configuration with a chiral purity ee of up to 100% and a total yield of 90% or more. The obtained axial chiral enantiomer of lesinurad in S configuration can reach a chiral purity ee of up to 99.9% and a total yield of 80% or more.

Resolution method for axis chiral enantiomers of lesinurad

The instant invention provides compounds of formula I which are PI3K-delta inhibitors, and as such are useful for the treatment of PI3K-delta-mediated diseases such as inflammation, asthma, COPD and cancer.

Purine inhibitors of human phosphatidylinositol 3-kinase delta

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Beijing, China

Deqian Bian