Optically pure sitagliptin phosphate monohydrate is efficiently and practically synthesized through a chiral hemiacetal as the key intermediate in 54% overall yield starting from (E)-4-(2,4,5-trifluorophenyl)but-2-enal and N-boc-protected hydroxylamine. The chiral hemiacetal fragment is constructed by a tandem aza-Michael/hemiacetal reaction catalyzed by an organocatalyst and the influence of acidity of Brønsted acid on tandem aza-Michael/hemiacetal reaction is researched in detail.

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Puquitinib mesylate is a novel phosphatidylinositol 3-kinases (PI3K) inhibitor, which has been shown to be effective in the treatment of cancer. A convenient protocol for the synthesis of the compound at kilogram scale is described, using 2,6-dichloropurine as starting material through amino-protection, S N 2 reaction with high regioselectivity, Buchwald-Hartwig coupling reaction, amino-deprotection and salt-forming reaction. The process is easy to operate and provides an effective way at kilogram scale produce with 48% yield in total.