Bristol-myers Squibb Compnay

Bristol-myers Squibb

Denis Favreau

Zhenrong Guo

Jack Z Gougoutas

John D DiMarco

Michael A Galella

Timothy M Malloy

Martha Davidovich

Imre M Vitez

Kathia Levesque

Robert Michael Borzilleri

Soong-Hoon Kim

Percy Sarwood Manchand

Joydeep Kant

Anthony J Cocuzza

Wendel William Doubleday

Shaopeng Wang

Shankar Swaminathan

John E Thornton

Markus Frieser

Shawn A Springfield

Yvonne Lear

Brian Leslie James

Wen Sen Li

Zhengrong Guo

Frederic Buono

Michel A Couturier

Michael Galella

The present disclosure generally relates to a process for synthesizing optionally substituted 1-chloro-4-methoxyisoquinolines. The present disclosure also relates to intermediates useful in this process.

Process for synthesizing substituted isoquinolines

There are provided in accordance with the present invention two crystalline polymorphs, designated Form A and Form B, respectively, as well as mixtures thereof, of an epothilone analog represented by the formula Also provided are methods of forming the novel polymorphs, therapeutic methods utilizing them and pharmaceutical dosage forms containing them.

Polymorphs of an epothilone analog

The present invention relates to a process for the preparation of epothilone analogs by initially forming novel ring-opened epothilones and carrying out a macrolactamization reaction thereon. The subject process is amenable to being carried out in a single reaction vessel without isolation of the intermediate compound and provides at least about a three-fold increase in yield over prior processes for preparing the desired epothilone analogs.

Process for the preparation of epothilone analogs

There are provided in accordance with the present invention two crystalline polymorphs, designated Form A and Form B, respectively, as well as mixtures thereof, of an epothilone analog represented by the formulaAlso provided are methods of forming the novel polymorphs, therapeutic methods utilizing them and pharmaceutical dosage forms containing them.

An improved method of synthesis of 21-amino epothilone derivatives which provides a one-pot conversion of 21-hydroxy epothilones to highly desirable 21-amino epothilones in high yield.

Method of preparation of 21-amino epothilone derivatives

The present invention provides temperature stable crystalline etoposide 4'-phosphate diethanol solvate, and a process for its preparation.

Crystalline etoposide 4'-phosphate diethanolate

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Saint-Hubert, Canada

Denis Favreau