E. R. Squibb Sons, Inc.

Bristol-myers Squibb Compnay

Bristol-myers Squibb

Jollie D Godfrey, Jr

Richard H Mueller

Janak Singh

Thomas P Kissick

Eric M Gordon

David R Kronenthal

Robert Zahler

Nachimuthu Soundararajan

Lawrence G Hamann

Ramesh N Patel

David John Augeri

David R Magnin

Ronald L Hanson

Jurong Yu

David B Brzozowski

Sergei Kolotuchin

Jason J Zhu

Jianji Wang

Truc Chi Vu

Mark D Schwinden

Rita Fox

John A Mazzullo

Kwok Wong

Katerina Leftheris

Alaric J Dyckman

Stephen T Wrobleski

John T Hynes

Gregory S Bisacchi

Sesha I Natarajan

John J Venit

Norma G Delaney

Toomas Mitt

Paul Alan Jass

John Anthony Grosso

Wendel William Doubleday

John L Dillon, Jr

Sushil K Srivastava

Keith Ramig

Zhongping Shi

Saibaba Racha

Thomas C Sedergran

Gerald L Powers

Atul S Kotnis

Philip Michael Sher

William N Washburn

Methods and compounds for production of cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV are provided.

Methods and compounds for producing dipeptidyl peptidase IV inhibitors and intermediates thereof

Methods of preparing kinase inhibiting pharmaceutical compounds having the formula (I): or a pharmaceutically acceptable salt or solvate thereof, wherein Rthrough Rand Z are as described in the specification. The methods according to the invention utilize an amination process, in which a pyrrole is reacted with a haloamine, preferably chloramine. This step is followed by cyclization to form the pyrrolotriazine core.

Methods for the preparation of pyrrolotriazine compounds useful as kinase inhibitors

Methods of preparing kinase inhibiting pharmaceutical compounds having the formula (I):or a pharmaceutically acceptable salt or solvate thereof, wherein Rthrough Rand Z are as described in the specification. The methods according to the invention utilize an amination process, in which a pyrrole is reacted with a haloamine, preferably chloramine. This step is followed by cyclization to form the pyrrolotriazine core.

2-hydroxy-3&mdash;(4-hydroxy-3-sulfonamidophenyl)&mdash;propylamines useful as beta 3 adrenergic agonists

Preparation of (S)-2-amino-6,6-dimethoxyhexanoic acid methyl ester via novel dioxolanes

Preparation of (s)-2-amino-6,6-dimethoxyhexanoic acid methyl ester via novel dioxolanes

The glycinamide of the formula (I) ##STR1## is reacted with the dioxolane of the formula (II) ##STR2## wherein L is a leaving group such as iodo, bromo, alkylsulfonyloxy, or arylsulfonyloxy to give the dioxolane of the formula (III) ##STR3## Treatment of (III) gives the dioxolane pentanoic acid IV ##STR4## which can be converted to (S)-2-amino-6,6-dimethoxyhexanoic acid, methyl ester.

Preparation of (S)-2-amino-6, 6-dimethoxyhexanoic acid methyl ester via

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

Homocysteine analogs of the formula ##STR1## wherein P.sub.1 is a nitrogen protecting group and R.sub.6 is alkyl, substituted alkyl or benzyl are prepared by esterifying N-protected L-methionine, oxidizing, treating the resulting sulfoxide with an acid anhydride, treating the resulting product with an alkali metal hydroxide followed by removal of formaldehyde and the treatment with an acid anhydride or acid halide. The L-homocysteine analogs are useful as intermediates in the preparation of compounds containing a fused bicyclic ring.

Process for preparing homocystein analogs useful as intermediates for

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 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

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Trenton, NJ, United States of America

Jollie D Godfrey, Jr