Syntex (u.s.a.) Inc.

Roche Colorado Corporation

F. Hoffmann-la Roche Ag

Syntex LLC

Hiralal N Khatri

George C Schloemer

Peter John Harrington

Michael P Fleming

Robert J Topping

Yeun-Kwei Han

Richard Robert Dauer

Jack Delbert Brown

Gary K Rowe

Dave A Johnston

David A Johnston

Eric Lodewijk

Bradley S DeHoff

L Mark Hodges

The invention provides methods of obtaining a peptide that include steps of synthesizing a peptide intermediate having one or more side chain protecting groups; providing a solvent to the peptide intermediate to form a peptide intermediate composition; and providing a precipitating agent in an amount sufficient to precipitate the peptide intermediate from the peptide intermediate composition, wherein the precipitating agent is an alcohol having three or more carbon atoms. Also provided are methods for precipitating peptides, methods for concentration peptides, and methods for filtering peptides.

Process and systems for recovery of peptides

Methods for the solid phase synthesis of T-1249 peptides and peptide intermediates, in particular methods involving synthesizing T-1249 peptide intermediates at low loading factors to produce products having excellent purity and yield.

Synthesis using peptide intermediate fragments

The present invention provides a method for preparing S-aryl cysteine. Specifically, the present invention provides enantioselective method for preparing S-aryl cysteine starting from cystine, cysteine or serine amino acid. The methods of the present invention provides S-aryl cysteine in enantiomeric excess of greater than about 96%.

Preparation of S-aryl-cysteine and its derivatives

5-Benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxamides of the formula

Preparation of ketorolac

The present invention provides a process for preparing 1,2-diheteroethylene sulfonamide of the formula: ##STR1## by reacting a pyrimidine monohalide of the formula: ##STR2## with a mono-protected 1,2-diheteroethylene anion of the formula M.sub.1 XCH.sub.2 CH.sub.2 YR.sub.5 and removing the protecting group, wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, Z, X, Y, M, M.sub.1 and W are defined herein.

Preparation of sulfonamides

The carbamate salt of 2-(2'-thienyl)-alkylamines and particularly the ethylamine and its method of synthesis are disclosed. The carbamate salt of 2-(2'-thienyl)ethylamine is a stable, easily transportable crystalline material that can be converted to 2-(2'-thienyl)ethylamine, a useful intermediate in the synthesis of 5[(2-chlorophenyl)methyl]-4,5,6,7-tetrahydrothieno-[3,2-c]pyridine hydrochloride, also known as ticlopidine hydrochloride. The synthesis is carried out by reacting an amine of formula (I): ##STR1## with CO.sub.2 in a hydrocarbon solvent to obtain the carbamate salt of formula II: ##STR2##

Carbamate salts of 2-(2'-thienyl)alkylamines

2,3-Dihydro-1H-pyrrolo[1,2-a]pyrrole-1,7-dicarboxylates of the formula, ##STR1## in which each R is independently H or lower alkyl, are prepared from from di(lower alkyl) 1,3-acetone-dicarboxylates.

Process for preparing

An improved process for the reduction of 2-(2-nitrovinyl)thiophene to form 2-(2-thienyl)ethylamine employs a boron-containing reducing agent, preferably diborane. The 2-(2-thienyl)ethylamine produced by this process is advantageously converted to ticlopidine.

2-(2-nitrovinyl)thiophene reduction and synthesis of

2,3-Dihydro-1H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid compounds of the formula, ##STR1## in which Y is OH;

2,3-Dihydro-1H-pyrrolo[1,2-a]pyrrole-1,7-dicarboxylates of the formula, ##STR1## in which each R is independently H or lower alkyl, are prepared from di(lower alkyl) 1,3-acetonedicarboxylates.

2,3-Dihydro-1H-pyrrolo[1,2-a]pyrrole-1,7-dicarboxylate intermediates of the formula, ##STR1## in which each R is independently H or lower alkyl, are prepared from di(lower alkyl) 1,3-acetonedicarboxylates.

2,3-Dihydro-1H-pyrrolo[1,2-a]pyrrole-1,7-dicarboxylates of the formula, ##STR1## in which each R is independently H or lower alkyl, are prepared from di(lower alkyl) 1,3-acetone-dicarboxylates.

Growing community of inventors

Louisville, CO, United States of America

Hiralal N Khatri