Unusual pyrimidine participation: efficient stereoselective synthesis of potent dual orexin receptor antagonist MK-6096
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Updated: Oct 13, 2026

Syntheses, Crystallization, and Spectroscopic Characterization of 3,5-Lutidine N-Oxide Dehydrate
Published on: April 24, 2018
John Y L Chung1, Yong-Li Zhong, Kevin M Maloney
1Process Chemistry, Merck Research Laboratories , P.O. Box 2000, Rahway, New Jersey 07065, United States and.
Abstract:
An asymmetric synthesis of dual orexin receptor antagonist MK-6096 (1) is described. Key steps for the trans-2,5-disubstituted piperidinyl ether fragment include a biocatalytic transamination, a trans-selective Mukaiyama aldol, and a regioselective pyridyl SNAr process. The pyrimidyl benzoic acid was synthesized via a Negishi coupling and a nitrile hydrolysis. Coupling of the two fragments via a catalytic T3P-mediated amidation completed the synthesis. Unusual behaviors in the hydrolysis of pyrimidyl benzonitrile and the amide coupling of the pyrimidyl benzoic acid are also described.
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