Bristol-myers Squibb Compnay

Edward J Gublo

Susan D Boettger

Padam N Sharma

Saibaba Racha

Gabriel M Galvin

Jun Li

Joydeep Kant

John J Usher

Rajendra P Deshpande

Jing Liang

Ulhas P Dhokte

Frank S Gibson

Karen L TenHuisen

Novel C-Calkyl- and aryl-thiotrifluoroacetates are provided which have the structure wherein Q is C-Calkyl or aryl, and are useful protecting agents for the amino or hydroxy functional groups of amines, amino acids or primary or secondary alcohols or amino alcohols to enable formation of amide bonds in peptides or proteins which are useful as screening agents, pharmaceuticals and cosmetics. A process for preparing C-Calkyl- and aryl-thiotrifluoroacetates is also provided wherein a C-Calkylthiol or arylthiol is treated with trifluoroacetic anhydride (TFAA) in the presence of organic base such as pyridine, a solvent such as dichloromethane (DCM) and dimethylaminopyridine (DMAP) as a catalyst to form the desired C-Calkyl- or aryl-thiotrifluoroacetate. In addition, a process for protecting a primary or secondary amino group or a primary or secondary hydroxyl group or an amino alcohol with a trifluoroacetyl protecting group is provided wherein a primary or secondary amine, amino acid, a primary or secondary alcohol or an amino alcohol is treated with a Cto Calkyl- or aryl-thiotrifluoroacetate in basic aqueous solution.

Alkyl and aryl-thiotrifluoroacetates and process

A process is provided for preparing a dipeptidyl peptidase IV inhibitor of the structure is treated with TFAA in isopropyl acetate to protect the tertiary hydroxyl group as a trifluoroacetate group to form 4 (which is a novel intermediate) which is converted to acid chloride compound 5 (which is a novel compound) using Vilsmeier reagent or other chloro reaget and coupled with compound 6 in a heterogeneous mixture of ethyl acetate and aqueous bicabonate to give compound 7 The N,O-bis(trifluoroacetyl) groups of compound 7 are deprotected to give free base compound 10.

Process for preparing a dipeptidyl peptidase IV inhibitor and intermediates employed therein

A process is provided for preparing a dipeptidyl peptidase IV inhibitor of the structure wherein is treated with TFAA in isopropyl acetate to protect the tertiary hydroxyl group as a trifluoroacetate group to form 4 (which is a novel intermediate)which is converted to acid chloride compound 5 (which is a novel compound)using Vilsmeier reagent or other chloro reagent and coupled with compound 6 in a heterogeneous mixture of ethyl acetate and aqueous bicarbonate to give compound 7 The N,O-bis(trifluoroacetyl) groups of compound 7 are deprotected to give free base compound 10.

A process is provided for preparing 4-alkyl- or 4-aryl-oxycarbonyl paclitaxel analogs which includes the steps of converting paclitaxel into a C-7 acylprotected paclitaxel employing an electrophilic protecting group, such as benzoyloxycarbonyl, and converting the C-7 protected analog into the 4-alkyloxycarbonyl or 4-aryloxycarbonyl paclitaxel analog. Novel intermediates produced in the process are also provided.

Process for preparing 4-alkyl- or 4-aryl-oxycarbonyl paclitaxel analogs and novel intermediates

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Liverpool, NY, United States of America

Edward J Gublo