E. R. Squibb Sons, Inc.

Bristol-myers Squibb Compnay

Bristol-myers Squibb

Eisai R&d Management Co., Ltd.

Bracco International Bv

Squibb & Sons, Inc.

Ermann, Peter H.

Mueller, Richard H.

Drossard, Jakob-matthias

Richard H Mueller

Janak Singh

Jollie D Godfrey, Jr

Thomas P Kissick

Michael A Poss

Shaopeng Wang

Paul D Pansegrau

Robert Zahler

John K Thottathil

Gregory S Bisacchi

Christopher M Cimarusti

David R Kronenthal

Nachimuthu Soundararajan

Toomas Mitt

Peter H Ermann

Yadagiri R Pendri

Thomas C Sedergran

Jakob-Matthias Drossard

Jagabandhu Das

Ramesh N Patel

Theodor Denzel

Philip Michael Sher

Laszlo J Szarka

John D Matiskella

Timothy P Connolly

Michael J Humora

Chung-Pin H Chen

John K Thottahil

Laxma Reddy Kolla

Paula L Kuester

Dejah T Petsch

John Kloss

Timothy Paul Connolly

Chung-Pin Chen

Yadagiri Pendri

Process for water soluble azole compounds

A purine salt of the formula ##STR1## wherein Y.sub.1 is chloro, bromo, or iodo, and R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are independently selected from alkyl and substituted alkyl is reacted with the compound of the formula

Process for preparing guanine-containing antiviral agents and purinyl

(1R,trans) Diprotected 3-methylene-1,2-cyclopropanedimethanol is oxidized to an optically active diol ##STR1## which is then cyclized to an orthoester ##STR2## This orthoester is then treated with a Lewis acid catalyst to give the cyclobutanone ##STR3## which is useful as an intermediate in the preparation of the antiviral agent �1R-(1.alpha.,2.beta.,3.alpha.)!-2-amino-9-�2,3-bis(hydroxymethyl)cyclobut yl!-1,9-dihydro-6H-purin-6-one.

Process for the preparation of an antiviral agent

A method of preparing compounds of the formula ##STR1## and pharmaceutically acceptable salts thereof which comprises converting a compound of the formula ##STR2## where the R.sup.2 substituent contains a hydrogen atom which is more acidic than the starred (*) hydrogen atom in formula II, to the corresponding dianion of formula ##STR3## where M is a counterion preferably lithium or magnesium, using two equivalents of a base in an inert solvent such as tetrahydrofuran; then reacting compounds of formula IIA with an epoxide of formula ##STR4## to produce the compounds of formula I.

Process for preparing 4-arylamino-benzopyran and related compounds

The present invention relates to novel 7-oxabicycloheptane carboxylic acid prostaglandin analog intermediates which may be used to prepare a final anti-thrombotic, anti-vasospastic product, and to methods for preparing the same.

7-oxabicycloheptane carboxylic acid prostaglandin analog intermediates

A purine salt of the formula ##STR1## wherein Y.sub.1 is chloro, bromo, or iodo, and R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are independently selected from alkyl and substituted alkyl.

Purinyl salts useful for preparing guanine containing antiviral agents

. A novel process comprises reducing a benzazepine or benzothiazepine at the 3-position in d-cis configuration by treatment with reductase-supplying microorganisms or enzymes derived therefrom. The process can be catalyzed in a single stage by growing microbial cultures or in a two-stage fermentation/transformation by resting cell-suspensions. The enzymes derived from the microorganisms can be used in free state or immobilized form. The microorganisms and enzymes catalyzes the specific reduction with 90 to 99% conversion efficiency to 99% or greater optical purity of the desired enantiomer.

Microbial reduction of benzazepines and benzothiazepine derivatives

A method is provided for preparing carboxylic acid intermediates of the structure ##STR1##

7-Oxabicycloheotane carboxylic acid prostaglandin analog intermediates

A method is provided for preparing homochiral maleimide intermediates of the structure ##STR1## wherein R.sup.7, R.sup.8 and R.sup.9 are as defined herein by reacting a homochiral amine of the structure ##STR2## with maleic anhydride and a silylating agent. The maleimide intermediate is used in the enantio-selective preparation of thromboxane A.sub.2 receptor antagonists.

Method for preparing homochiral maleimide intermediates, via silylation

A process for preparing compounds of the formula ##STR1## where a, b, c, R.sub.1, R.sub.2, and R.sub.3 are as defined herein including the step of alkylating a phenol of formula ##STR2## with an acetylene of formula ##STR3## where X is chlorine; bromine; --OC(O)--R.sub.5, where R.sub.5 is alkyl, aryl or substituted aryl; or --OCO.sub.2 R.sub.6, where R.sub.6 is alkyl or ##STR4## in the presence of a catalytic amount of a cuprous or cupric salt. The compounds of formula I are intermediates useful in the preparation of pyranyl cyanoguanidine derivatives.

Process for the preparation of intermediates useful in the preparation

Racemic Feist's acid is treated with (R)-(+) -.alpha.-methylbenzylamine to yield (1R-trans)-3-methylene -cyclopropane-1,2-dicarboxylic acid, (R)-.alpha.-methylbenzyl-amine (1:1) salt. This salt can then be converted to (1R-trans)-3-methylene-1,2-cyclopropanedicarboxylic acid, dimethyl ester which is an intermediate in the preparation of the antiviral agent [1R-(1.alpha.,2.beta.,3.alpha.)]-2-amino-9-[2,3-bis(hydroxymethyl)cyclobut yl]-1,9-dihydro-6H-purin-6-one. The improved process also enables the recovery of racemic Feist's acid from the resolution.

The protected cyclobutanone of the formula ##STR1## is treated with a dialkylaluminum chloride, an alkylaluminum dichloride, a trialkylaluminum compound, hydrogen in the presence of the catalysts ruthenium black or ruthenium on alumina, diphenyl-silane in the presence of tris(triphenylphosphine) rhodium (I) chloride, or iridium tetrachloride to yield the corresponding diprotected cyclobutanol. This compound is useful as an intermediate in the preparation of antiviral agents.

Process for preparing

7-oxabicycloheptane carboxylic acid protaglandin analog intermediates

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Ringoes, NJ, United States of America

Richard H Mueller