Schering Corporation

Baxter International Inc.

Baxter Healthcare Sa

Merck Sharp + Dohme Corp.

Hong-Chang Lee

Wenxue Wu

George G Wu

Frank Xing Chen

George S K Wong

David Jieh-Shyh Tsai

Jennifer Ann Vance

William W Leong

Tiruvettipuram K Thiruvengadam

Xiaoyong Fu

Tao Wang

Nanfei Zou

Jeffrey Manning Eckert

John S Chiu

Jing Liao

Peter C Nirchio

Bosco D'Sa

Paitoon Rashatasakhon

Nolan C Erickson

Shen-Chun Kuo

Kartik M Keertikar

Kevin Joseph Klopfer

Ilia A Zavialov

George S Wong

Loc Thanh Tran

Juergen Weber

Linas V Kudzma

Feng Liang

Hoa N Nguyen

Vilas Hareshwar Dahanukar

Yongxian Zeng

Leonid A Rozov

Ji Xie

Ramani R Raghavan

Weidong Tong

Man Zhu

Tetsuo Iwama

David J S Tsai

Xiongwei Shi

Ronald Bell

Yi Liu

Shannon Zhao

Vijay Sabesen

Cecelia Proietti

Cecilia Proietti

Jeffrey M Eckert

George SK Wong

Jennifer A Vance

Zou Nanfei

Xiongwei Shih

A method of purifying crude sevoflurane comprising (i) providing crude sevoflurane and an aqueous base to a first centrifugal separator, wherein the crude sevoflurane comprises sevoflurane and hexafluoroisopropanol; (ii) mixing the crude sevoflurane and the aqueous base in the first centrifugal separator; and (iii) separating the sevoflurane from the aqueous base in the first centrifugal separator, thereby purifying the crude sevoflurane.

Methods of purifying crude sevoflurane

A method for cleaning a distilling column includes providing a distilling column including a packing containing nickel and adding hydrochloric acid to the distilling column to wash at least a portion of the packing, thereby cleaning the distilling column.

Methods for cleaning distilling columns

The present invention provides for a process for preparing racemic methyl 6,6-dimethyl-3-azabicyclo[3,1,0]hexane-2-carboxylate, its corresponding salt: (1R,2S,5S)-methyl 6,6-dimethyl-3-azabicyclo[3,1,0]hexane-2-carboxylate di-p-toluoyl-D-tartaric acid ('D-DTTA') salt or a (1S,2R,5R)-methyl 6,6-dimethyl-3-azabicyclo[3,1,0]hexane-2-carboxylate di-p-toluoyl-L-tartaric acid salt ('L-DTTA') in a high enantiomeric excess. This invention also provides for a process for preparing a (1R,2S,5S)-methyl 6,6-dimethyl-3-azabicyclo[3,1,0]hexane-2-carboxylate dibenzoyl-D-tartaric acid (&#x201c;D-DBTA&#x201d;) salt or a (1S,2R,5R)-methyl 6,6-dimethyl-3-azabicyclo[3,1,0]hexane-2-carboxylate L-tartaric acid (&#x201c;L-DBTA&#x201d;) salt in a high enantiomeric excess. Further, this invention provides a process for preparing intermediates II, IIB, III, IV, IV salt, V, VI, and VII.

Process for the preparation of 6,6-dimethyl-3-azabicyclo-[3.3.0]-hexane compounds and enantiomeric salts thereof

The present invention relates also to a process for the preparation of intermediate compounds useful in preparing the compounds of Formula (I) using the process of Scheme (II). 

Process for preparing (1R,2S,5S)-N-[(1S)-3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]-3-[(2S)-2-[[[(1,1-dimethylethyl)amino]-carbonyl]amino]-3,3-dimethyl-1-oxobutyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide

Disclosed is a process for the synthesis of compounds of Formula I by sequentially aminating, first with a primary amine and then with a secondary amine, an intermediate compound of the structure of Formula E1, wherein Ris a linear, branched, or cyclic alkyloxy functional group of the structure (&#x2014;R&#x2014;OH), Ris a linear, branched or cyclic alkyl group, Ris a linear, branched or cyclic alkyl group, and Ris an alkylene-heterocycle, said process comprising forming intermediate compound of Formula E1 by reacting, in a refluxing reaction solvent selected from alcohols having 5 or less carbon atoms and mixtures of two or more thereof, a methanol solution of a salt of a 4-alkyl-3-amino-pyrazole compound of Formula C1, with a diamidization reagent selected from dimethylmalonate, monomethylmalonyl-chloride, and malonyl dichloride in the presence of a Lewis base having sufficient proton affinity to abstract a proton from the 1-position nitrogen on the pyrazole ring.

Process and intermediates for the synthesis of (3-alkyl-5-piperidin-1-yl-3,3a-dihydro-pyrazolo[1,5-a]pyrimidin-7-yl)-amino derivatives and intermediates

The present invention is directed to the synthesis of 4-[4-[(R)-[1-[cyclopropylsulfonyl)-4-piperidinyl](3-fluorophenyl)methyl]-3(S)-methyl-1-piperazinyl]-1-[(4,6-dimethyl-5-pyrimidinyl)carbonyl]-4-methylpiperidine], and intermediates therefor from readily available starting materials by a novel route.

Synthesis of CCR5 receptor antagonists

The present invention provides for a process for preparing racemic methyl 6,6-dimethyl-3-azabicyclo[3,1,0]hexane-2-carboxylate, its corresponding salt: (2S, 3R, 4S)-methyl 6,6-dimethyl-3-azabicyclo[3,1,0]hexane-2-carboxylate di-p-toluoyl-D-tartaric acid ('D-DTTA') salt or a (2R, 3S, 4R)-methyl 6,6-dimethyl-3-azabicyclo[3,1,0]hexane-2-carboxylate di-p-toluoyl-L-tartaric acid salt ('L-DTTA') in a high enantiomeric excess. This invention also provides for a process for preparing a (2S, 3R, 4S)-methyl 6,6-dimethyl-3-azabicyclo[3,1,0]hexane-2-carboxylate dibenzoyl-D-tartaric acid (&#x201c;D-DBTA&#x201d;) salt or a (2R, 3S, 4R)-methyl 6,6-dimethyl-3-azabicyclo[3,1,0]hexane-2-carboxylate L-tartaric acid (&#x201c;L-DBTA&#x201d;) salt in a high enantiomeric excess. Further, this invention provides a process for preparing intermediates II, IIB, III, IV, IV salt, V, VI, and VII.

Process for the preparation of 6,6-dimethyl-3-azabicyclo-[3.1.0]-hexane compounds and enantiomeric salts thereof

The present invention relates to an improved process for preparing himbacine analogs. The compounds are useful as thrombin receptor antagonists. The improved process may allow for at least one of easier purification by crystallization, easier scalability, and improved process yield on the desired enantiomer. An example of a step in the synthesis of such a himbacine analog is as follows: 

Synthesis of himbacine analogs

The present invention is generally directed to a process to directly prepare pharmaceutically acceptable salts enriched with respect to selected rotameric salts of a basic compound, by creative choice of an acid and a solvent medium. The process is particularly useful in preparing specific rotamers of pharmaceutically useful salts in desired preponderance of a rotamer.

Preparation of pharmaceutical salts of piperazine compounds

Growing community of inventors

Livingston, NJ, United States of America

Hong-Chang Lee