Schering Corporation

Merck Sharp + Dohme Corp.

John S Chiu

William J Greenlee

Samuel Chackalamannil

Tiruvettipuram K Thiruvengadam

Chou-Hong Tann

Cesar Colon

Xiaoyong Fu

Tao Wang

Jing Liao

Timothy L McAllister

Wenxue Wu

Michael D Green

Hong-Chang Lee

Michael J Green

Junning Lee

Paul E McNamara

Michael P Graziano

David Jieh-Shyh Tsai

Charles G Eckhart

David J S Tsai

John K Jenkins

Teddy Kosoglou

T K Thiruvengadam

Stanley Rosenhouse

Richard E Youngstrom

Madhu Chintala

Anastasia Pavlovsky

Susan Bogdanowich-Knipp

Thiruvengadam K Thiruvettipuram

A process is provided for preparing azetidinones useful as intermediates in the synthesis of penems and as hypocholesterolemic agents, comprising reacting a &#x3b2;-(substituted-amino)amide, a &#x3b2;-(substituted-amino)acid ester, or a &#x3b2;-(substituted-amino)thiolcarbonic acid ester with a silylating agent and a cyclizing agent selected from the group consisting of alkali metal carboxylates, quaternary ammonium carboxylates, quaternary ammonium hydroxides, quaternary ammonium alkoxides, quaternary ammonium aryloxides and hydrates thereof, or the reaction product of: (i) at least one quaternary ammonium halide and at least one alkali metal carboxylate; or (ii) at least one quaternary ammonium chloride, quaternary ammonium bromide, or quaternary ammonium iodide and at least one alkali metal fluoride, wherein a quaternary ammonium moiety of the cyclizing agent is unsubstituted or substituted by one to four groups independently selected from the group consisting of alkyl, arylalkyl and arylalkyl-alkyl.

Process for the synthesis of azetidinones

This application discloses provides a process for the introduction of nitro-group functionality into a compound which contains also a site of unsaturation and/or oxygen functionality by direct (one step) oxidation of an oxime functional group mediated by a molybdenum VI/VII peroxo complex, the process comprising:  Where Rand Rare as defined above.

Synthesis of 3-(5-nitrocyclohex-1-enyl) acrylic acid and esters thereof

The present invention relates to an improved process for preparing himbacine analogs. The compounds are useful as thrombin receptor antagonists. The improved process may allow for at least one of easier purification by crystallization, easier scalability, and improved process yield on the desired enantiomer. An example of a step in the synthesis of such a himbacine analog is as follows: 

Synthesis of himbacine analogs

This invention provides a process for preparing the hypocholesterolemic compound

There is disclosed a novel formylating agent, 2-formylmercaptobenzothiazole.

2-formylmercaptobenzothiazole

An improved process for converting gentamicin B to isepamicin comprising forming 3,6'-di-N-formylgentamicin B, acylating the 1-amino group with an N-protected (S)-isoserine compound and removing all the blocking groups under conditions which result in high yields of isepamicin. A novel formylating agent, 2-formylmercaptobenzothiazole, and intermediate compounds are also disclosed.

Process for preparing isepamicin

Process for preparing albuterol, acetal, hemi-acetal, and hydrates of

A high yielding process for converting 3,2',6'-tri-N-acetyl sisomicin to netilmicin comprising the step of silylating the starting material at the 5,2' positions, and optionally at the 4' position, converting the 1-amino substituent to a 1-N-imino substituent, converting the imino to an ethylamino, deprotecting the compound and recovering netilmicin. Also disclosed are novel intermediate compounds.

Process for preparing netilmicin

A novel, stable, crystalline sodium (5R,6S,8R)-6-(1-hydroxyethyl)-2-(2-carbamoyloxyethylthio)-penem-3-carboxyl ate (designated as Form II) is prepared by forming a homogenous solution of sodium (5R,6S,8R)-6-(1-hydroxyethyl)-2-(2-carbamoyloxyethylthio)-penem-3-carboxyl ate combined with stirring the homogenous solution for a time and at a temperature sufficient to produce Form II and recovering Form II. Form II may also be prepared by contacting a first solution obtained by dissolving (5R,6S,8R)-6-(1-hydroxyethyl)-2-(2-carbamoyloxyethylthio)-penem-3-carboxyl ic acid in dimethylacetamide with a second solution obtained by dissolving a sodium salt of an organic acid having a pKa of up to about 5, e.g., sodium 2-ethylhexanoate in acetone, in the presence of at least 5 volume percent water while stirring the reaction mixture so formed at a temperature and for a time sufficient to produce Form II followed by recovering Form II. Form II exhibits a greater physical stability and increased solid state chemical stability and reduced hygroscopicity over that of the amorphous form (e.g., Form I) which renders Form II greatly superior to Form I as a clinically suitable antibacterial agent.

Crystalline sodium (5R, 6S,

Growing community of inventors

Parsippany, NJ, United States of America

John S Chiu