Dupont Pharmaceuticals Company

Bristol-Myers Squibb Pharma Company

Other

Dupont Pharmaceuticals, Inc.

Bristol-Myers Squibb Pharma Corporation

Joseph M Fortunak

Zhe Wang

Jianguo Yin

Luigi Anzalone

Gregory D Harris

Mona Patel

Rodney Lawrence Parsons, Jr

Robert E Waltermire

Benjamin R P Stone

Ioannis I Valvis

Hui-Yin Li

Lilian Alicia Radesca

Jaan A Pesti

Louis Storace

William Aloysius Nugent

Michael B Maurin

Roberta L Dorow

Silvio Campagna

George F Huhn

Patrick J Sheeran

Goss S Kauffman

Akin H Davulcu

Rodney L Parsons

This invention relates generally to the asymmetric synthesis of quinazolin-2-ones that are useful as inhibitors of HIV reverse transcriptase. The synthesis is accomplished through the chiral ligand mediated addition of cyclopropylacetylide.

Asymmetric synthesis of quinazolin-2-ones useful as HIV reverse transcriptase inhibitors

4,4-disubstituted-1, 4-dihydro-2H-3, 1-benzoxazin-2-ones useful as HIV reverse transcriptase inhibitors and intermediates and processes for making the same

Preparation of asymmetric cyclic ureas through a monoacylated diamine intermediate

The present invention relates generally to novel methods for the preparation of cyclopropylacetylene which is an essential reagent in the asymmetric synthesis of (S)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one; a useful human immunodeficiency virus (HIV) reverse transcriptase inhibitor with superior anti-retroviral activity. In the process, for example, cyclopropane carboxaldehyde is alkylated to form 1,1,1-trichloro-2-cyclopropyl-ethanol; which in turn undergoes elimination to form 1,1-dichloro-2-cyclopropyl-ethene; which in turn undergoes elimination to form cyclopropyl acetylene.

Process for the preparation of cyclopropylacetylene

The present invention relates to benzoxazinones of formula I:

4,4-disubstituted-1,4-dihydro-2h-3,1-benzoxazin-2-ones useful as HIV reverse transcriptase inhibitors and intermediates and processes for making the same

The present invention relates generally to novel methods for the synthesis of cyclopropylacetylene which is an essential reagent in the asymmetric synthesis of (S)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one; a useful human immunodeficiency virus (HIV) reverse transcriptase inhibitor. In the process, cyclopropane carboxaldehyde is condensed with malonic acid to form 3-cyclopropylacrylic acid; 3-cyclopropylacrylic acid is halogenated to form (E,Z)-1-halo-2-cyclopropylethylene; and (E,Z)-1-halo-2-cyclopropylethylene is dehydrohalogenated to form cyclopropyl acetylene. This improvement provides for high conversion of inexpensive, readily available starting materials into cyclopropylacetylene, high overall yields and can be conducted on an industrial scale.

The present invention relates generally to novel methods for the synthesis of cyclopropylacetylene which is an essential reagent in the asymmetric synthesis of (S)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one; a useful human immunodeficiency virus (HIV) reverse transcriptase inhibitor. In the process, for example, cyclopropane carboxaldehyde is alkylated to form 1,1,1-trichloro-2-cyclopropyl-ethanol; which in turn is hydroxy protected to form 1,1,1-trichloro-2-cyclopropylethyltosylate; which in turn undergoes elimination to form cyclopropyl acetylene. This improvement provides for high conversion of inexpensive, readily available starting materials into cyclopropylacetylene, high overall yields and can be conducted on an industrial scale.

The present invention relates to processes for the synthesis of a crystalline polymorph of 10,10-Bis((2-fluoro-4-pyridinyl)methyl)-9(10H)-Anthracenone in high purity. The product is useful in the synthesis of pharmaceutical compounds for the reduction of cholinergic system dysfunction.

Crystalline 10,10-Bis((2-fluoro-4-pyridinyl)methyl)-9(10H)-Anthracenone and an improved process for preparing the same

Processes for the preparation of &lsqb;S-(R,S)&rsqb;-N-&lsqb;1,3-benzodioxol-5-yl)butyl&rsqb;-3,3-diethyl-2&lsqb;4-&lsqb;4-methyl-1-piperazinyl)carbonyl&rsqb;phenoxy&rsqb;-4-oxo-l-azetidine carboxamide, a useful inhibitor of human leukocyte elastase (HLE), are described. The process including (a) contacting a compound of formula (II):

Efficient process for the preparation of &lsqb;S-(R,S)&rsqb;-N-&lsqb;1,3-benzodioxol-5-yl)butyl&rsqb;-3,3-diethyl-2&lsqb;4-&lsqb;4-methyl-1-piperazinyl)carbonyl&rsqb;phenoxy&rsqb;-4-oxo-1-azetidine carboxamide, a human leukocyte elastase inhibitor

The present invention relates to benzoxazinones of formula I: ##STR1## or stereoisomeric forms or mixtures, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of HIV reverse transcriptase, and to pharmaceutical compositions and diagnostic kits comprising the same, methods of using the same for treating viral infection or as an assay standard or reagent, and intermediates and processes for making the same.

4,4-disubstituted-1,4-dihydro-2H-3,1-benzoxazin-2-ones useful as HIV

The present invention relates generally to novel methods for the synthesis of cyclopropylacetylene which is an essential reagent in the asymmetric synthesis of (S)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-ben zoxazin-2-one; a useful human immunodeficiency virus (HIV) reverse transcriptase inhibitor. In the process, cyclopropane carboxaldehyde is condensed with malonic acid to form 3-cyclopropylacrylic acid; 3-cyclopropylacrylic acid is halogenated to form (E,Z)-1-halo-2-cyclopropylethylene; and (E,Z)-1-halo-2-cyclopropylethylene is dehydrohalogenated to form cyclopropyl acetylene. This improvement provides for high conversion of inexpensive, readily available starting materials into cyclopropylacetylene, high overall yields and can be conducted on an industrial scale.

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Newark, DE, United States of America

Joseph M Fortunak