Merck + Co., Inc.

Merck Sharp + Dohme Corp.

Alex Minhua Chen

Andrey V Peresypkin

William K Hagmann

Mark T Goulet

Ping Liu

Linus S Lin

James Patrick Jewell

Artis Klapars

Kevin Campos

Robert Wenslow

Lisa F Frey

Yaling Wang

Terence G Hamill

H Donald Burns

Raymond E Gibson

Russell R Ferlita

J Christopher McWilliams

Cheng-Yi Chen

Karl Hansen

C Scott Shultz

Robert M Wenslow, Jr

Robert M Wenslow

Debra J Wallace

Stephen Howard Cypes

Ivan Lee

Vicky K Vydra

The present invention relates to particular radiolabeled Cannabinoid-1 (CB1) receptor modulators, and methods of using these modulators for labeling and diagnostic imaging of Cannabinoid-1 receptors in mammals, particularly humans. In addition, intermediates useful for the synthesis of the radiolabeled Cannabinoid-1 receptor modulators are also disclosed, as well as the processes for synthesizing the radiolabeled Cannabinoid-1 receptor modulators. Still further, formulations of the radiolabeled Cannabinoid-1 receptor compounds are described.

Radiolabeled cannabinoid-1 receptor modulators

The present invention is directed to a practical process for the preparation of an enamide (II) by palladium catalyzed coupling of a primary amide (IV) with a compound of structural formula (III), as shown below: As well as to crystalline forms of a compound produced by this process, in particular, an anhydrous crystal form, Form B, and crystalline solvates falling into three patterns, Type 1, Type 2, and Type 3, and crystalline intermediate compounds produced in the process. Still further, the present invention relates to the stereoselective reduction of the tetrasubstituted enamide (II) to the corresponding amide (I).

Formation of tetra-substituted enamides and stereoselective reduction thereof

The dihydrogenphosphate salt of 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro [1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine is a potent inhibitor of dipeptidyl peptidase-IV and is useful for the prevention and/or treatment of non-insulin dependent diabetes mellitus, also referred to as type 2 diabetes. The invention also relates to a crystalline monohydrate of the dihydrogenphosphate salt as well as a process for its preparation, pharmaceutical compositions containing this novel form and methods of use for the treatment of diabetes, obesity, and high blood pressure.

Phosphoric acid salt of a dipeptidyl peptidase-IV inhibitor

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Metuchen, NJ, United States of America

Alex Minhua Chen