Merck + Co., Inc.

Other

Merck Sharp + Dohme Corp.

Louis S Crocker

James A McCauley

Andrew S Thompson

John M Williams

Ian W Davies

Raymond Cvetovich

Daniel Richard Sidler

Joseph Kukura, Ii

Michael D Ward

Steven D Young

Andrew Kotliar

Ronald B Jobson

Dongwei Cai

Karel M J Brands

Amar J Mahajan

Richard G Osifchin

Christine Stelmach

Elizabeth S Fisher

Thomas R Verhoeven

Kai Rossen

Robert D Larsen

Ulf H Dolling

Philip J Pye

Robert Wenslow

Gerald S Brenner

Hsien-Hsin Tung

Chris H Senanayake

Karel M Brands

Karen C Thompson

Jonathan D Rosen

Karel M Jos Brands

Brian K Johnson

Todd D Nelson

Robert M Wenslow, Jr

Chad Dalton

Charles Orella

Robert M Wenslow

Hossain Jahansouz

Jiang Wang

Sophie Dorothee Clas

Daniel R Sidler

Ronald Jobson

Joseph L Ii Kukura

William Clarke

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

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

The instant invention describes a method for crystallizing (&#x2212;)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one from a solvent and anti-solvent solvent system and producing the crystalline product. The desired final crystal form, Form I, can be produced when using methanol or ethanol. Form II is isolated from 2-propanol and can be converted to the desired crystal form at low drying temperatures, such as between about a temperature of 40&#xb0; C. and 50&#xb0; C.

Crystal forms of (-)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one

Polymorphic, amorphous and hydrated forms of the title compound having the following structure:are disclosed. The compound is a potent and selective cyclooxygenase-2 (COX-2)inhibitor.

Polymorphic, amorphous and hydrated forms of 5-chloro-3-(4-methanesulfonylphenyl)-6'-methyl-[2,3&#x2032;]bipyridinyl

5-chloro-3-(4-methanesulfonylphenyl)-6&prime;-methyl-&lsqb;2,3&prime;&rsqb;bipyridinyl in pure crystalline form and process for synthesis

The instant invention describes a method for crystallizing (&minus;)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one from a solvent and anti-solvent system and producing the crystalline product. The desired final crystal form, Form I, can be produced when using methanol or ethanol. Form II is isolated from 2-propanol and can be converted to the desired crystal form at low drying temperatures, such as between about a temperature of 40&deg; C. and 50&deg; C.

Crystal Forms of (-)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one

This invention is concerned with a novel polymorphic form of the compound 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-phenyl)-ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine which is a tachykinin receptor antagonist useful in the treatment or prevention of disorders of the central nervous system, inflammatory diseases, pain or migraine, asthma, and emesis. The instant polymorphic form has advantages over the other known forms of 2-(R)-(1-(R)-(3,5-bis(trifluoro-methyl)-phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine in terms of thermodynamic stability and suitability for inclusion in pharmaceutical formulations.

Polymorphic form of a tachykinin receptor antagonist

The present invention is concerned with 4-benzyl-2-hydroxy-1,4-oxazin-3-one, and novel processes for the preparation therof. This compound is useful as an intermediate in the synthesis of compounds which possess pharmacological activity.

4-Benzyl-2-hydroxy-1,4-oxazine-3-one and polymorphic forms thereof

Polymorphic, amorphous and hydrated forms of 5-chloro-3-(4-methanesulfonyphenyl)-6'- methyl-&lsqb;2,3'&rsqb;bipyridinyl

This invention is concerned with a novel polymorphic forms of the compound 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)4-( 5-(dimethyl-amino)methyl-1,2,3-triazol-4-yl)methyl-3-(S)-(4-fluorophenyl)morpholine hydrochloride which is a tachykinin receptor antagonist useful in the treatment or prevention of disorders of the central nervous system, inflammatory diseases, pain or migraine, asthma, and emesis. The instant polymorphic forms have advantages over the other known forms of 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)4-( 5-(dimethylamino)methyl-1,2,3-triazol-4-yl)methyl-3-(S)-(4-fluorophenyl)morpholine hydrochloride in terms of thermodynamic stability and suitability for inclusion in pharmaceutical formulations.

This invention is concerned with a novel polymorphic form of the compound 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-phenyl)-ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine which is a tachykinin receptor antagonist useful in the treatment or prevention of disorders of the central nervous system, inflammatory diseases, pain or migraine, asthma, and emesis. The instant polymorphic form has advantages over the other known forms of 2-(R)-(1-(R)-(3,1-bis(trifluoro-methyl)-phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine in terms of thermodynamic stability and suitability for inclusion in pharmaceutical formulations.

This invention is concerned with a novel polymorphic form of the compound 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-phenyl)-ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine which is a tachykinin receptor antagonist useful in the treatment or prevention of disorders of the central nervous system, inflammatory diseases, pain or migraine, asthma, and emesis. The instant polymorphic form has advantages over the other known forms of 2-(R)-(1-(R)-(3,,5-bis(trifluoro-methyl)-phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine in terms of thermodynamic stability and suitability for inclusion in pharmaceutical formulations.

This invention is concerned with a novel polymorphic form of the compound 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-phenyl)-ethoxy)-3-(S)-(4-fluoro)phe nyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine which is a tachykinin receptor antagonist useful in the treatment or prevention of disorders of the central nervous system, inflammatory diseases, pain or migraine, asthma, and emesis. The instant polymorphic form has advantages over the other known forms of 2-(R)-(1-(R)-(3,5-bis(trifluoro-methyl)-phenyl)ethoxy)-3-(S)-(4-fluoro)phe nyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine in terms of thermodynamic stability and suitability for inclusion in pharmaceutical formulations.

Growing community of inventors

Belle Mead, NJ, United States of America

Louis S Crocker