Bristol-myers Squibb Compnay

Bristol Meyers Squibb Company

Viiv Healthcare UK (no. 4) Limited

Matthew R Hickey

Francisco Gonzalez-Bobes

Joerg Deerberg

Antonio Ramirez

Martin D Eastgate

David Kenneth Leahy

Xinhua Qian

Bin Zheng

Thomas E La Cruz

Yu Fan

Scott A Savage

Kana Yamamoto

Thomas M Razler

Keming Zhu

Ye Zhu

Collin Chan

Alina Borovika

Maxime C D Soumeillant

Chris Sfouggatakis

Nathan R Domagalski

Serge Zaretsky

Hong Geun Lee

Burcu Selin Aytar

Michael David Bengt Fenster

Wendy Wangying Yang

Robert V Forest

Benjamin Cohen

Michael S Bultman

Rebecca A Green

Nathaniel David Kopp

Kathleen Lauser

Helen Y Luo

Francisco Gonzalez-bobes

David K Leahy

Maxime CD Soumeillant

The invention generally relates to an improved process for the preparation of N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-3-(7-tert-butylpyrazolo[1,5-a][1,3,5]triazin-4-ylamino)-2-oxopyrrolidin-1-yl)cyclohexyl)acetamide, 

Process for the preparation of N-((1R,2S,5R)-5-(-butylamino)-2-((S)-3-(7--butylpyrazolo[1,5-a][1,3,5]triazin-4-ylamino)-2-oxopyrroldin-1-yl)cyclohexyl)acetamide

The present disclosure provides an additive system for use in protein PEGylation. The additive system includes p-aminobenzoic hydrazide used either alone or in combination with aromatic amines, such as 3,5-diaminobenzoic acid, or with ammonium salts such as ammonium chloride or ammonium acetate. The disclosed additive combination provides several benefits including increased reaction rates, higher yields and reduction in the aminoxy-PEG equivalents required to complete the conjugation reaction. Typical reactions can be run by combining the additive or additive system with a solution of a protein and aminoxy-PEG reagent. The solution is adjusted to pH 4 and held at 20-25&#xb0; C. without stirring until completion, typically within 24 hours.

Additive systems for use in protein PEGylation

A process for preparing halogenated azaindole compounds makes use of stable reagents including a brominating reagent, a boroxine and a sulfonic anhydride to enhance the selectivity and yield of the final product. In addition, the process is associated with various other advantages, including the ability to recycle reagents, cost reduction, and improved manufacturability.

Process for preparing halogenated azaindole compounds using boroxine

A process is provided for preparing 4-(8-(2-chlorophenoxy)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)bicyclo[2.2.1]heptan-1-ol and novel intermediates used in the process. The compound is a 11-beta hydroxysteroid dehydrogenase type I inhibitor which exhibits activity in the treatment of various metabolic diseases.

Process for the preparation of 4-(8-(2-chlorophenoxy)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)bicyclo[2.2.1]heptan-1-ol and novel intermediates therefor

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Yardley, PA, United States of America

Matthew R Hickey