Bristol-myers Squibb Pharma Company

Dupont Pharmaceuticals Company

Bristol-myers Squibb Compnay

The Dupont Merck Pharmaceutical Company

Philip Ma

Jiacheng Zhou

Hui-Yin Li

Pasquale N Confalone

Lynette May Oh

Paul E Aldrich

Richard A Earl

Jaan A Pesti

Charles G Clark

Robert Dicosimo

Biao Jiang

William Frank Degrado

Jianguo Yin

Lucius Thomas Rossano

Michael B Maurin

Lin-Hua Zhang

Goss S Kauffman

Lucius T Rossano

Lin Hua Zhang

Chris Teleha

Randall K Ward

David John Meloni

A novel process and intermediates thereof for making 4,5-dihydro-pyrazolo[3,4-c]pyrid-2-ones of the type shown below from appropriate phenyl hydrazines is described. These compounds are useful as factor Xa inhibitors.

Synthesis of 4,5-dihydro-pyrazolo[3,4-c]pyrid-2-ones

The present invention relates to processes for the production of &#x3b1;-aryl-&#x3b2;-ketonitriles, which serve as synthetic intermediates in the preparation of a series of biologically important molecules such as corticotropin releasing factor (CRF) receptor antagonists.

Convergent synthesis of &#x3b1;-aryl-&#x3b2;-ketonitriles

A novel process and intermediates thereof for making 4,5-dihydro-pyrazolo[3,4-c]pyrid-2-ones of the type shown below from appropriate phenyl hydrazines is described.These compounds are useful as factor Xa inhibitors.

Synthesis of 4,5-dihydro-pyrazolo [3,4-c] pyrid-2-ones

The present invention relates to processes for the production of &agr;-aryl-&bgr;-ketonitriles, which serve as synthetic intermediates in the preparation of a series of biologically important molecules such as corticotropin releasing factor (CRF) receptor antagonists.

Convergent synthesis of &agr;-aryl-&bgr;-ketonitriles

The present invention relates to a process for the enantioselective enzymatic aminolysis of racemic 2-&lsqb;3-(4-cyanophenyl)-4,5-dihydro-5-isoxazolyl&rsqb;acetate ((R/S)-I) by methyl N -Boc-L-&agr;,&bgr;-diaminoproprionate.p-toluenesulfonic acid. More specifically, this invention pertains to a process for the enantioselective enzymatic aminolysis of racemic isobutyl 2-&lsqb;3-(4-cyanophenyl)-4,5-dihydro-5-isoxazolyl&rsqb;-acetate by methyl N -Boc-L-&agr;,&bgr;-diaminoproprionate.p-toluene sulfonic acid to produce (R)-methyl-3-&lsqb;&lsqb;&lsqb;3-(4-cyanophenyl)-4,5-dihydro-5-isoxazolyl&rsqb;acetyl&rsqb;amino&rsqb;-N-(butoxycarbonyl)-L-alanine, an intermediate in the preparation of roxifiban, an isoxazoline-based platelet glycoprotein IIb/IIIa antagonist which has activity as an antithrombotic agent.

Enantioselective enzymatic aminolysis of a racemic 2-isoxazolylacetate alkyl ester

The present invention relates to processes for the conversion of nitriles to amidines in the preparation of compounds which are antagonists of the platelet glycoprotein IIb/IIIa fibrinogen receptor complex. The compounds described herein are potent thrombolytics and useful for the inhibition of platelet aggregation in the treatment of thromboembolic disorders.

Efficient method for the conversion of nitriles to amidines

The present invention provides of method of preparing phenyl-substituted azoles. This method uses an efficient ligand-accelerated Ullmann coupling reaction of anilines with azoles. The coupling products are useful for preparing factor Xa inhibitors.

Efficient ligand-mediated Ullmann coupling of anilines and azoles

Synthesis of 1,3,5-trisubstituted pyrazoles

The present invention relates to processes for the conversion of nitrites to amidines in the preparation of compounds which are antagonists of the platelet glycoprotein IIb/IIIa fibrinogen receptor complex. The compounds described herein are potent thrombolytics and useful for the inhibition of platelet aggregation in the treatment of thromboembolic disorders.

A novel process for making 1,3,5-trisubstituted pyrazoles of the type shown below from appropriate phenyl hydrazines is described.

The potent platelet glycoprotein IIb/IIIa antagonist, roxifiban, is produced in crystalline form. Crystalline roxifiban exists in two polymorphic forms, designated Form 1 and Form 2. These polymorphic forms are characterized by x-ray powder diffraction and solid-state carbon NMR. Pharmaceutical compositions and methods for the treatment or prevention of diseases mediated by platelet aggregation are described.

Crystalline roxifiban

Efficient method for the conversion of nitriles to amidines and species thereof

The present invention relates to processes for the production of .alpha.-aryl-.beta.-ketonitriles, which serve as synthetic intermediates in the preparation of a series of biologically important molecules such as corticotropin releasing factor (CRF) receptor antagonists.

Convergent synthesis of .alpha.-aryl-.beta.-ketonitriles

A novel process for making compounds of Formula I, ##STR1## wherein X is a leaving group selected from the group Br, Cl, TsO, MsO, and TfO and R is a 1,2-diol, from a compound of Formula II: ##STR2## is described.

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West Chester, PA, United States of America

Philip Ma