Merck + Co., Inc.

Daniel Richard Sidler

John M Williams

Robert D Larsen

Ralph P Volante

Raymond Cvetovich

Louis S Crocker

Michael D Ward

Ulf H Dolling

James M McNamara

Ronald B Jobson

Karel M J Brands

Amar J Mahajan

James J Bergan

Mahadevan Bhupathy

Elizabeth S Fisher

Michael A Patane

Kai Rossen

Gerald F Bills

Ian W Davies

Michel M Chartrain

Philip J Pye

Steven A Weissman

Edward G Corley

Robert Wenslow

Michael J Kaufman

Colleen S Taylor

Norihiro Ikemoto

Hsien-Hsin Tung

Mark S Jensen

Wenjie Li

William A Hunke

Nancy Sue Barta

Christopher Roberge

David C Dubost

Jess Sager

Joseph Kukura, Ii

Jean-Francois Marcoux

Brian K Johnson

Ashok Maliakal

Robert M Wenslow, Jr

Charles Orella

Essa Hsinyi Hu

Jeffrey A Zimmerman

Paul A Bergquist

Lisa M DiMichele

Robert M Wenslow

A process for preparing a crystalline, carbapenem monosodium salt of formula IIa:characterized by the steps a) adding about 10 to 30% of an organic solvent to an aqueous solution of the carbapenem, b) cooling the resulting solution to less than &#x2212;5&#xb0; C., c) adjusting the pH using a solution containing an acid in an organic solvent to give the appropriate pH for crystallization, and d) crystallizing the compound by adding methanol, and a Calcohol at between &#x2212;5 and &#x2212;25&#xb0; C.

Crystalline forms of carbapenem antibiotics and methods of preparation

An efficient synthesis for the preparation of ((1R,3S)-3-isopropyl-3-{[3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl]carbonyl} cyclopentyl)[(3S,4S)-3-methoxytetrahydro-2H-pyran-4-yl]amine and its succinate salt are provided. The succinate salt is crystalline and has superior properties.

CCR-2 antagonist salt

A process for preparing a crystalline, carbapenem monosodium salt of formula IIa: characterized by the steps a) adding about 10 to 30% of an organic solvent to an aqueous solution of the carbapenem, b) cooling the resulting solution to less than &#x2212;5&#xb0; C., c) adjusting the pH using a solution containing an acid in an organic solvent to give the appropriate pH for crystallization, and d) crystallizing the compound by adding methanol, and a Calcohol at between &#x2212;5 and &#x2212;25&#xb0; C.

The present invention relates to a process for reducing the levels of organic solvents to pharmaceutically acceptable levels in thermally unstable crystalline carbapenem solids represented by formula I:or a salt thereof, wherein Rand R, are the same or different, and are selected from H, alkyl, aryl, and heteroaryl, comprising washing a carbapenem solid containing organic solvent with an organic solvent containing water; and using vacuum and/or inert gas (hydrated or dry) at low temperature to produce a compound of formula I containing pharmaceutically acceptable levels of organic solvents, wherein the water content of the crystalline carbapenem solid, correcting for organic solvents, is maintained at about 13% to about 25% during the process.

Process for making carbapenem compounds

A process for preparing a &bgr;-hydroxy carbamate product is disclosed. The process comprises reacting an olefin compound containing at least one carbon-carbon double bond with a carbamate in an aqueous solvent and in the presence of a base, an osmium catalyst, a co-oxidant selected from a halohydantoin, a haloisocyanuric acid, and an alkali metal salt of a haloisocyanuric acid, and optionally an asymmetric ligand, to form a reaction mixture containing the &bgr;-hydroxy carbamate product. The process optionally further comprises treating the &bgr;-hydroxy carbamate product with additional base to form an oxazolidinone. The oxazolidinones are useful as chiral auxiliary agents and as intermediates for the formation of pharmaceutically active substances such as alpha 1 a adrenergic receptor antagonists. A process for preparing nitrogen-functionalized derivatives of the oxazolidinones is also disclosed.

Process for preparing &bgr;-hydroxycarbamates and their conversion to oxazolidinones

This invention relates to crystalline pharmaceutically acceptable salts of an alpha 1a adrenergic receptor antagonist, Compound A, which are useful in the treatment of benign prostatic hyperplasia. Pharmaceutical compositions employing the crystalline salts, and processes for making and using the crystalline salts and pharmaceutical compositions of Compound A are also disclosed. This invention further relates to a process for obtaining enantiomerically pure intermediate useful for the synthesis of end product alpha 1a adrenergic receptor antagonists. The end product compounds are useful for the treatment of benign prostatic hyperplasia and for relaxing lower urinary tract tissue. The invention also relates to a process for preparing a class of dihydropyrimidinone compounds of which Compound A is a member, wherein the process involves deprotonating a dihydropyrimidinone compound and then coupling the deprotonated derivative with a primary amine.

Alpha 1a adrenergic receptor antagonists

The present invention relates to a process for the preparation of a compound of formula (I) or a sodium salt thereof

Process for the preparation of leukotriene antagonists

Enzymatic process of making alpha 1a adrenergic receptor antagonists using protease

The invention encompasses a process for making compounds of Formula I useful in the treatment of cyclooxygenase-2 mediated diseases. ##STR1##

Process for making 2-aryl-3-aryl-5-halo pyridines useful as COX-2

A pharmaceutical composition is disclosed which contains a compound of formula I: ##STR1## or a pharmaceutically acceptable salt, prodrug or hydrate thereof, in the stabilized form and/or in combination with a carbon dioxide source.

Carbapenem antibiotic

The present invention provides a process for forming 5-(alkyl or alkoxy)carbonyl-6-alkyl-4-(aryl or alkyl)-3,4-2(1H)-dihydropyrimidinones by combining a .beta.-keto ester or diketone, an aldehyde and urea in the presence of a boron reagent, a metal salt (e.g., Cu.sub.2 O) and a catalyst (e.g., acid). The reaction is typically run in one pot in a solvent to afford dihydropyrimidinones in higher yields and with easier work up than previously known methods.

Process for making dihydropyrimidinones

The present invention relates to a process for the preparation of a compound of formula (I) or a sodium salt thereof ##STR1## wherein HET is 7-chloroquinolin-2-yl or 6,7-difluoroquinolin-2-yl, which comprises: reacting the dilithium dianion of 1-(mercaptomethyl)cyclopropaneacetic acid with a compound of formula (II) ##STR2## wherein HET is as defined above and L is arylsulfonyl or alkylsulfonyl. The invention further provides the dicyclohexylamine salt of a compound of formula (I).

Process for the preparation of leukotriene anatgonists

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Whitehouse Station, NJ, United States of America

Daniel Richard Sidler