Merck + Co., Inc.

Dupont Pharmaceuticals Company

Other

Merck Sharp + Dohme Corp.

Merck Frosst Canada, Inc.

Merck Canada Inc.

Cheng Yi Chen

Lushi Tan

Richard D Tillyer

Dalian Zhao

Robert D Larsen

Paul O'Shea

Feng Xu

Michael Ernest Pierce

Lilian Alicia Radesca

Anusuya Choudhury

Thomas R Verhoeven

Paul N Devine

Edward J Grabowski

Guy R Humphrey

Paul J Reider

Ian W Davies

Hongmei Li

Michael J Zacuto

Weirong Chen

Bangping Xiang

Xin Wang

Kelvin Yong

Greg Hughes

Edward J J Grabowski

Matthew Thomas Tudge

Philippe Dagneau

Anthony On-Ping King

Bruce S Foster

Sarah Dolman

Jongrock Kong

Paul O'shea

The present invention relates to macrolactam compounds, intermediates useful in the preparation of macrolactams, methods for preparing the intermediates, and methods for preparing and modifying macrolactams. One use of the compounds and methods described herein is in the production of macrolactam compounds able to inhibit HCV NS3 protease activity. An example of an HCV inhibitory compound that can be synthesized using the procedures described herein is Compound A and derivative thereof.

Process and intermediates for preparing macrolactams

This invention describes a reductive amination process whereby perfluorinated ketones or ketals are combined with &#x3b1;-aminoesters under basic conditions to form metal carboxylates. Diastereoselective reductions of the metal carboxylates enable access to two diastereomers, depending on the reducing conditions.

Diastereoselective reductive amination process

Synthesis of ketosulfone esters

This invention encompasses a novel process for synthesizing compounds represented by formula A:

Synthesis of methylthiophenyl hydroxyketones

Described is a process of preparing 3-aryl, 4-aryloxy furan-5-ones which are useful as inhibitors of cyclooxygenase-2 (COX-2). Such compounds are useful as anti-inflammatory agents. The process is directed to an asymmetric synthesis which involves: a trisubstituted styrene derivative preparation via Horner-Wadsworth-Emmons reaction and subsequent one pot trifluoromethylation of the allylic alcohol; preparation of the .alpha.-hydroxyl ketone using Sharpless asymmetric dihydroxylation and Swern oxidation; the esterification of the .alpha.-hydroxyl ketone with the phenoxy acetic acid; and the Dieckman condensation of the resulting ester.

Process of making 3-aryloxy, 4-aryl furan-2-ones useful as inhibitors of

The present invention provides novel methods for the asymmetric synthesis of (S)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1- benzoxazin-2-one of formula (VI-i) ##STR1## which is useful as a human immunodeficiency virus (HIV) reverse transcriptase inhibitor.

Asymmetric synthesis of benzoxazinones

An efficient method for the preparation of key intermediate, in the synthesis of (-)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-ben zoxazin-2-one, a reverse transcriptase inhibitor is achieved using a chiral addition reaction to the 4-chloro-2-trifluoromethylketoaniline with an organozinc complex to give the desired alcohol. This instant method has broad applicability in the chiral addition to any prochiral ketone.

Efficient enantioselective addition reaction using an organozinc reagent

A process for enhancing the purity of 2R-�1-hydroxy-1-trifluoromethyl-3-cyclopropylpropyn-2-yl!-4-chloroaniline comprising the formation of an acid addition salt which is capable of rejecting the racemate in the selected organic solvent.

Process for enhancing the optical purity

An efficient method for the quantitative preparation and isolation of a compound of formula I ##STR1## or its enantiomer, a chiral mediator used in enantioselective synthesis.

Efficient synthesis of a chiral mediator

A new process is described for the synthesis of the triazolyl tryptamine: ##STR1## and related compounds. The process involves a palladium-catalyzed ring closure between a substituted ortho-iodoaniline and a protected 1-alkynol. The process is carded out at high temperature, e.g. 100.degree. C., in a dry inert solvent, e.g., DMF and in the presence of a proton acceptor, e.g., Na.sub.2 CO.sub.3 or a trialkylamine. The triazolyl tryptamine, as well as acid addition salts thereof, is a 5 HT.sub.1 D receptor agonist having anti-migraine properties.

Palladium catalyzed ring closure of triazolyltryptamine

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Colonia, NJ, United States of America

Cheng Yi Chen