Merck + Co., Inc.

Merck Sharp + Dohme Corp.

Banyu Pharmaceutical Co. Ltd

Lisa F Frey

Richard D Tillyer

David M Tschaen

Ulf H Dolling

Edward J Grabowski

Artis Klapars

Yoshiaki Kato

Yi Zhang

Nobuyoshi Yasuda

Paul N Devine

Yong-Li Zhong

Kevin Campos

Edward Cleator

Jeremy Peter Scott

Robert A Reamer

Robert Wenslow

Richard Desmond

Yaling Wang

Bryon Ladd Simmons

J Christopher McWilliams

Eric Ashley

Cheng-Yi Chen

Andrey V Peresypkin

Edward J J Grabowski

Alex Minhua Chen

Baoqiang Wan

John Simon Edwards

C Scott Shultz

Peter Richard Mullens

Courtney K Maguire

Andrew Brunskill

Debra J Wallace

Peter G Dormer

Pu Qian

Stephane G Ouellet

The present invention is directed to Compounds of Formula (I) and salts thereof, wherein R, R, Rand Rare defined above herein. The present invention is also directed to uses of the compounds of Formula (I) to add phosphoramidate groups onto organic alcohols. 

Substituted phosphoramidate compounds and uses thereof

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

A rearrangement process for the preparation of a 6,5,5-tricyclic, a 6,6,5-tricyclic and 6,5,5,7-tetracyclic ring system is disclosed.

Rearrangement process and tricyclic and tetracyclic compounds

This invention relates to a key intermediate in the synthesis of an endothelin antagonist and the synthesis of this key intermediate using an asymmetric conjugate addition reaction.

Asymmetric conjugate addition reaction

An efficient method for the preparation of a compound of (-)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-ben zoxazin-2-one, also known as DMP-266, a reverse transcriptase inhibitor is achieved using a cyclization reaction of the amino alcohol intermediate with an alkyl or aryl chloroformate and a base.

Efficient synthesis of A 1,4-dihydro-2H-3,1-benzoxazin-2-one

This invention relates to a key intermediate in the synthesis of an endothelin antagonist, the synthesis of this key intermediate and the synthesis of an endothelin antagonist using this intermediate in a stereoselective deoxygenation reaction.

Stereoselective deoxygenation reaction

An efficient method for the preparation of a compound of (-)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl- 1,4-dihydro-2H-3, 1-benzoxazin-2-one, also known as DMP-266, a reverse transcriptase inhibitor is achieved using a cyclization reaction of the amino alcohol intermediate with an alkyl or aryl chloroformate and a base.

Efficient synthesis of a 1,4-dihydro2H-3,1-benzoxazin-2-one

Compounds formed by an asymmetric conjugate addition reaction

The invention encompasses a process for making compounds of Formula I useful in the treatment of inflammation and other cyclooxygenase-2 mediated diseases.

Process of preparing phenyl heterocycles useful as COX-2 inhibitors

A simple, high yielding synthesis of a-chloro ketones is described, involving acylation of Grignard and organolithium reagents with N-methoxy-N-methylchloroacetamide. The efficiency of the process is further enhanced by recycling N,O-dimethylhydroxylamine.

Synthesis of .alpha.-chloro or fluoro ketones

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Somerset, NJ, United States of America

Lisa F Frey