Merck + Co., Inc.

Paratek Pharmaceuticals, Inc.

Raymond Cvetovich

Joseph S Amato

John M Williams

Louis S Crocker

Daniel Richard Sidler

Michael D Ward

Tadeusz Warchol

Ronald B Jobson

Karel M J Brands

Amar J Mahajan

Mallory F Loewe

Elizabeth S Fisher

Ulf H Dolling

Richard John Varsolona

Michel M Chartrain

James A McCauley

Robert Wenslow

George G Hazen

Hsien-Hsin Tung

Karel M Brands

Frederick W Hartner

Christopher Roberge

Richard J Demchak

Joseph Kukura, Ii

Brian K Johnson

Fuh-Rong Tsay

Robert M Wenslow, Jr

John Leazer

Yoshiko Yodogawa

Tomoyuki Asai

Charles Orella

Robert M Wenslow

Daniel R Sidler

Ronald Jobson

Daniel Sidler

Joseph Ii Kukura

Louis Crocker

Crystalline forms, including salts and polymorphs, of a compound useful in the treatment of tetracycline compound-responsive states are provided herein. The crystalline compounds are useful for the treatment or prevention of conditions and disorders such as bacterial infections and neoplasms, as well as other known applications for tetracycline compounds in general.

Salts and polymorphs of a tetracycline compound

Salts and polymorphs of 9-(2,2-dimethylpropyl-aminomethyl) minocycline

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 present invention is concerned with a novel process for the preparation of 1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-one (CAS 30071-93-3). This compound is useful as an intermediate in the synthesis of therapeutic agents.

Process for the synthesis of 1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-one

The present invention is concerned with a novel process for the preparation of 3,5-bis(trifluoromethyl)benzoic acid (CAS 725-89-3). This compound is useful as an intermediate in the synthesis of compounds which possess pharmacological activity, in particular, as substance P (neurokinin-1) receptor antagonists.

Process for the synthesis of 3,5-bis(trifluoromethyl)benzoic acid

The most thermodynamically stable crystalline form of the benzoic acid salt of 4&Prime;-deoxy-4&Prime;-epi-methylamino avermectin B1a/B1b as the hemihydrate is obtained by crystallization from organic solvents containing a controlled amount of water.

Thermodynamically stable crystal form of 4&Prime;-deoxy-4&Prime;-epi-methylamino avermectin B1a/B1b benzoic acid salt and processes for its preparation

The present invention is concerned with a novel process for the preparation of 1-(3,5-bis(trifluromethyl)phenyl)ethan-1-one (CAS 30071-93-3). This compound is useful as an intermediate in the synthesis of therapeutic agents.

Process for the synthesis of 1-(3,5-bis(trifluoromethyl)-phenyl)ethan-1-one

The present invention is concerned with a novel process for the preparation of 3,5-bis(trifluoromethyl)bromobenzene (CAS 328-70-1). This compound is useful as an intermediate in the synthesis of compounds which possess pharmacological activity.

Process for the synthesis of 3,5-bis(trifluoromethyl)-bromobenzene

The present invention relates to the process for the preparation of the substituted azetidinone having the formula: ##STR1## comprising a convergent synthesis wherein the azetidinone portion of the molecule is coupled to the lower benzodioxole portion via a base catalyzed addition to an isocyanate.

Process for preparing substituted azetidinones

The present invention relates to a process for converting a racemic mixture of 3,3-diethyl-4-[(4-carboxy)phenoxy]-2-azetidinone esters into the corresponding (S)-acid using lipase derived from Pseudomonas sp. The process provides the target acid in high enantiomeric excess.

Enzymatic hydrolysis of 3,3-diethyl-4-[(4-carboxy)phenoxy]-2-azetidinone

An improved process for formation of a 5-oxime on avermectin derivatives comprises the treatment of the oxo-compound with hydroxylamine in aqueous isopropanol at pH 1.8-2.1.

Process for 4'-epi-acetylamino-4'-deoxy-5-oximinoavermectin B.sub.1

A stereocontrolled glycosidation with thiophenyl 4-(N-allyloxycarbonyl)-epi-methylamino-4-deoxyoleandrose and 5-O-allyloxycarbonyl avermectin B.sub.1 monosaccharide using N-iodosuccinimide produces exclusively the .alpha.-anomer of a precursor of 4'-epi-methylamino-4'-deoxyavermectin B.sub.1 in 90% yield. Deprotection and crystallization as the benzoic acid salt yields 4'-epi-methylamino-4'-deoxyavermectin B.sub.1 (emamectin benzoate), a potent insecticide.

Glycosidation route to 4'-epi-methylamino-4'-deoxyavermectin B.sub.1

There is disclosed a novel form of avermectin compounds wherein the avermectin compounds are crystallized as alcohol solvates to greatly enhance stability of the avermectin drug during long-term storage. The avermectin compounds have utility as highly potent antiparasitic, insecticidal, and anthelmintic agents and compositions for that use are also disclosed.

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Scotch Plains, NJ, United States of America

Raymond Cvetovich