Merck + Co., Inc.

Dongwei Cai

Thomas R Verhoeven

Robert D Larsen

Joseph F Payack

Louis S Crocker

David L Hughes

Michel Journet

Lihu Yang

Changyou Zhou

David M Tschaen

Ian Frank Cottrell

Richard Desmond

Mark S Jensen

Wenjie Li

Yao-Jun Shi

Min Ge

Fred Fleitz

Scott Hoerrner

Jiang Wang

Gary Javadi

Sylvain Levac

Dorian Nelson

Robert D Larson

Elizabeth Szumigala

Jason Kowal

The present invention provides 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-m ethoxytetrahydro-2H-pyran-4-yl]amine and its succinate salt. The present invention additionally provides an efficient syntheses for the preparation of intermediates (3R)-3-methoxytetrahydro-4H-pyran-4-one; (1S,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-ene-1-carboxylic acid; and 3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine; and for the preparation of the precursor (3S,4S)-N-((1S,4S)-4-isopropyl-4-{[3-(tri-fluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl]carbonyl}cyclopent-2-en-1-yl)-3-methoxytetrahydro-2H-pyran-4-amine. The invention additionally resides in the superior properties of the succinate salt of ((1R,3S)-3-isopropyl-3-1{[3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl]carbonyl}cyclopentyl)[(3S,4S)-3-methoxytetrahydro-2H-pyran-4-yl]amine 

Process for the preparation of CCR-2 antagonists

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

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.

Polymorphic form of a tachykinin receptor antagonist

A process of synthesizing a compound of the formula 1:

Process of synthesizing binaphthyl derivatives

The present invention is directed to the compound 4-N,N-dimethylaminomethyl-5-formyl-1,2,3-triazole which is a valuable intermediate in the preparation of phamaceutical compounds. The present invention is further directed to a novel convergent process for the preparation 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 which is a potent and selective substance P (or neurokinin-1) receptor antagonist useful as a therapeutic agent.

Convergent process for the preparation of a morpholine compound

The present invention is concerned with a novel linear process for the preparation 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 which is a potent and selective substance P (or neurokinin-1) receptor antagonist usefull as a therapeutic agent.

Linear process for the preparation of a morpholine compound

The present invention is directed to a process for the preparation of the reagent dimethyl titanocene (Cp.sub.2 Ti(CH.sub.3).sub.2) from titanocene dichloride (Cp.sub.2 TiCl.sub.2) and a methyl magnesium halide, in particular, methyl magnesium chloride (CH.sub.3 MgCl). The instant process provides the desired reagent in a manner which is generally less hazardous and more economical than previous methods.

Process for the preparation of dimethyl titanocene

The present invention is directed to a process of making spirocycles of general structural formula: ##STR1## where R.sub.1 is selected from the group consisting of CO--C.sub.1-3 alkyl, cyano, carboxy, carboxy C.sub.1-6 alkyl ester, carboxamide, C.sub.1-6 alkyl sulfinyl, C.sub.1-6 alkyl sulfonyl, C.sub.1-6 methanesulfonamide and halogen; R.sub.2 is selected from the group consisting of keto or alcohol, R.sub.3 is cyano, resulting in compounds which are Class III antiarrhythmic.

Process of making spirocycles and analogs thereof

A process of synthesizing a compound of the formula 1: ##STR1## is disclosed, which comprises reacting a compound of the formula 2: ##STR2## with diphenylphosphine in the presence of an amine base and a nickel catalyst to produce a compound of formula 1.

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Edison, NJ, United States of America

Dongwei Cai