Ampac Fine Chemicals LLC

Aerojet Fine Chemicals LLC

Onyx Pharmaceuticals, Inc.

Pharmachem Technologies Limited

Btg International Limited

Olivier Dapremont

Aslam A Malik

Der-Shing Huang

Patrick Berget

George R Gettys

Andrew S Thompson

Alexander James Bridges

Sean Dalziel

James Robert Zeller

Hasan Palandoken

Joy A Stringer

Brian R Morgan

James Alan Kerschen

Ali Suleman

William Dubay

DerShing Huang

Antonio Romero

Jeffrey D Butler

Hyunjung Kim

Xa Her

Darin Sanchez

Sean Mark Dalziel

Compounds and methods for preparing substituted 3-(1-amino-2-methylpentane-3-yl)phenyl compounds from an isomerically pure starting material are described. In particular, methods of preparing a 3-(1-(dimethylamino)-2-methylpentane-3-yl)phenol as a substantially optically pure (R,R) stereoisomer are described. Using a method of the present invention, only the (R,R) and (S,S) stereoisomers of the target compound are produced, increasing the yield and stereoselectivity of the desired (R,R) stereoisomer.

Compounds and methods for preparing substituted 3-(1-amino-2-methylpentane-3-yl)phenyl compounds

A method of producing 6-amino-cyclopenta[g]quinazolines, in enantiomerically enriched form, is provided. In particular, the method may be applicable to the synthesis of N&#x2014;{N-{4-[N-((6S)-2 -hydroxymethyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclo-penta[g]quinazolin-6-yl)-N-(prop-2 -ynyl)amino]benzoyl}-L-&#x3b3;-glutamyl}-D-glutamic acid (ONX-0801). 

Synthesis of cyclopentaquinazolines

Product yields in chemical reactions that produce a solid product from a liquid reaction mixture are improved by chromatographically separating certain key impurities from the product mixture prior to crystallization, or from the filtrate after crystallization in which case further product is crystallized from the filtrate. The removal of key impurities either before the first crystallization or between the first and second crystallizations facilitates the crystallization of product to produce a higher yield of product.

Reaction systems with incorporated chromatography units for enhanced product recovery

High yields and purity are obtained in the purification of enantiomers of chiral carboxylic acids by preparative-scale chromatography by including a tertiary alcohol in the mobile phase in conjunction with an acidic modifier and a hydrophobic solvent. The tertiary alcohol is superior to other, more commonly used alcohols by reducing the extent of esterification of the enantiomer that otherwise lowers the yield and the purity.

Preparative-scale separation of enantiomers of chiral carboxylic acids

A halide salt of a 1-(hydroxyiminomethyl-1-pyridino)-3-(halomethyl)-2-oxapropane is prepared by adding a pyridinealdoxime to a bis-halomethylether in such a manner that the bis-halomethylether is maintained in excess throughout the addition. This procedure produces the halide salt of a 1-(hydroxyiminomethyl-1-pyridino)-3-(halomethyl)-2-oxapropanein high yield and purity, which facilitates its use as an intermediate in the manufacture of an asymmetrically substituted 1,3-di(1-pyridino)-2-oxapropane, a class of compounds that are generally useful antidotes to various toxic agents. A prominent member of the class is the dimethylsulfonate salt of 1-(2-hydroxyiminomethyl-1-pyridino)-3-(4-carbamoyl-1-pyridino)-2-oxapropane. The use of mercaptoalkyl-functionalized polymers is disclosed as a preferred metal ion scavenger for a final purification step in the manufacture of these compounds.

Process for halomethyl ethers of hydroxyiminomethyl quaternary pyridinium salts

Simulated moving bed (SMB) chromatography involving a series of columns serially connected in a circuit is performed in a modified protocol by dividing the columns into two groups isolated from flow communication with each other and using one of the two groups solely for extraction of the more strongly retained component from the solid phase while the other group is operated in the conventional SMB manner. The sites of introduction and withdrawal and the site of division between the two groups of columns are all rotated around the circuit as in conventional SMB chromatography, but the process is capable of separating component mixtures with non-linear isotherms and of extracting solutes that are very strongly retained on the solid phase.

Simulated moving bed chromatography for strongly retained compounds

A halide salt of a 1-(hydroxyiminomethyl-1-pyridino)-3-(halomethyl)-2-oxapropane is prepared by adding a pyridinealdoxime to a bis-halomethylether in such a manner that the bis-halomethylether is maintained in excess throughout the addition. This procedure produces the halide salt of a 1-(hydroxyiminomethyl-1-pyridino)-3-(halomethyl) -2-oxapropanein high yield and purity, which facilitates its use as an intermediate in the manufacture of an asymmetrically substituted 1,3-di (1-pyridino)-2-oxapropane, a class of compounds that are generally useful antidotes to various toxic agents. A prominent member of the class is the dimethylsulfonate salt of 1-(2-hydroxyiminomethyl-1-pyridino)-3 -(4-carbamoyl-1-pyridino)-2-oxapropane. The use of mercaptoalkyl-functionalized polymers is disclosed as a preferred metal ion scavenger for a final purification step in the manufacture of these compounds.

The present invention provides, inter alia, a novel process for the preparation of Citalopram, a known antidepressant.

Process for the preparation of Citalopram intermediate

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Cameron Park, CA, United States of America

Olivier Dapremont