Merck Sharp + Dohme Corp.

Schering Corporation

Jianguo Yin

Xiaoyong Fu

Timothy L McAllister

Shuyi Zhang

Nobuyoshi Yasuda

Agnes S Kim-Meade

Jason L Winters

Anantha R Sudhakar

Joseph E Lynch

Frank Xing Chen

Yong-Li Zhong

Doris P Schumacher

Carmela Molinaro

Kelvin Yong

W Peter Wuelfing

Teresa Andreani

Kevin Michael Belyk

Ilia A Zavialov

Bangping Xiang

Arthur G Taveras

Michael P Dwyer

David J Blythin

Younong Yu

Tiruvettipuram K Thiruvengadam

Ho-Jane Shue

Richard John Varsolona

Rongze Kuang

Shen-Chun Kuo

Xiao Chen

Peter Emmanuel Maligres

Kevin Joseph Klopfer

Kevin Campos

Zhuqing Liu

Edward Cleator

Scott Trzaska

Alexei Kalinin

Jingjun Yin

Zhijian Liu

Tetsuji Itoh

Michael R Reeder

Xiaoming Chen

Mengwei Hu

Kenneth Stanley Matthews

Mathew Thomas Maust

Gerald Werne

Melodie Deniz Christensen

Vincenzo Liotta

Andrew Brunskill

Mark Weisel

Frank Bruno Guenter

Thiruvettipuram K Thiruvengadam

Timothy D Cutarelli

Chee-Wah Tang

Zaher Shabani

Kelvin H Yong

Kevin M Belyk

Timothy Mcallister

The present invention relates to processes for the preparation of N-protected (2S,5R)-6-hydroxy-7-oxo-N-piperidin-4-yl-1,6-diazabicyclo[3.2.1]octane-2-carboxamide intermediates. Such compounds have application in the preparation of beta-lactamase inhibitors such as 7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamides and esters, in particular, the beta lactamase inhibitor, (2S,5R)-7-oxo-N-piperidin-4-yl-6-(sulfoxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide. The present invention also encompasses intermediates useful in the disclosed processes and methods for their preparation.

Process for preparing beta-lactamase inhibitor hydroxylurea intermediates

The present invention is directed to processes for preparing Substituted Tetracyclic Heterocycle Compounds of formula (I): (I) which may be useful as HCV NS5A inhibitors. The present invention is also directed to compounds that may be useful as synthetic intermediates and catalysts in the processes of the invention. 

Process for preparing substituted tetracyclic heterocycle compounds

The invention encompasses a novel process for making piperidinone carboxamide indane and azainane derivatives, which are CGRP receptor antagonists useful for the treatment of migraine.

Intermediates for preparing CGRP receptor antagonists

Process for making CGRP receptor antagonists

The invention encompasses a novel process for making piperidinone carboxamide indane and azainane derivatives, which are CGRP receptor antagonists useful for the treatment of migraine, utilizing a highly effective spiroacid synthesis.

The disclosure encompasses a novel process for making piperidinone carboxamide indane and azainane derivatives, having less steps and improved yields as compared to previous synthetic methods for making these compounds, which are CGRP receptor antagonists, useful for the treatment of migraine. Conditions for an amide bond formation between an acid and amine include for example reacting the compounds of Formulae B (after salt break) and C with an amide coupling reagent and optionally an additive and an acid and/or a base in a non-reactive solvent.

This application discloses a novel process for the preparation of 1,2-substituted 3,4-dioxo-1-cyclobutene compounds, which have utility, for example, in the treatment of CXC chemokine-mediated diseases, and intermediates useful in the synthesis thereof.

Process and intermediates for the synthesis of 1,2-substituted 3,4-dioxo-1-cyclobutene compounds

This application discloses a novel process for the preparation of phosphonate esters useful as intermediates in the preparation of himbacine analogs, themselves useful as thrombin receptor antagonists. The chemistry taught herein can be exemplified by the following scheme: wherein Ris selected from alkyl, aryl heteroaryl and arylalkyl groups having 1 to 10 carbon atoms, and Ris selected independently for each occurrence from alkyl, aryl heteroaryl and arylalkyl groups having 1 to 10 carbon atoms and hydrogen, Xis Cl, Br, or I; Xis selected from Cl and Br; and PdLis a supported palladium metal catalyst or a soluble heterogeneous palladium catalyst. The L-derivatizing reagent is a moiety which converts the alcohol functional group of compound 137D to any leaving group which can be displaced by a triorgano-phosphite phosphonating agent.

Synthesis of diethyl{[5-(3-fluorophenyl)-pyridine-2yl]methyl}phosphonate

The present invention relates to four distinct crystalline polymorphs of a monohydrate of Compound A having the following chemical structure:  These four polymorphic forms, herein referred to as Forms I, II, III and IV are active as a CXC-chemokine receptor ligands. The invention is further directed to formulations, methods of treatment, and processes of synthesis of these polymorphic forms.

Crystalline polymorphs of a CXC-chemokine receptor ligand

This application discloses a novel process to synthesize 2-(Quinolin-5yo)-4,5-Disubstituted-Azole derivatives, which may be used, for example, as PDE IV inhibitor compounds in pharmaceutical preparations.

Process and intermediates for the synthesis of 2-(quinolin-5-yl)-4,5 disubstituted-azole derivatives

Disclosed are maleate, tosylate, fumarate, and oxalate salts of the compound 5-(1(S)-Amino-2-Hydroxyethyl)-N-[(2,4-Difluorophenyl)-Methyl]-2-[8-Methoxy-2-(Trifluoromethyl)-5-Quinoline]-4-Oxazolecarboxamide, represented by Formula I, and methods of preparing the same.

Maleate, tosylate, fumarate and oxalate salts of 5-(1-(S)-amino-2-hydroxyethyl)-N-[(2,4-difluorophenyl)-methy]-2-[8-methoxy-2-(triflouromethy)-5-quinoline]-4-oxazolecarboxamide and preparation process therefore

Disclosed is a process for making the compound of formula I: using the compounds of formulas II, Q, and XI or XII: wherein A is selected from the group consisting of Br, Cl and I (with Br being preferred); and R represents (C-C)alkyl. Also disclosed are intermediate compounds that are made in the disclosed process.

Synthesis of 2-Hydroxy-N,N-dimethyl-3-[[2-[[1(R)-(5-methyl-2-furanyl)propyl]amino]-3,4-dioxo-1-cyclobuten-1-yl]amino]benzamide

Synthesis of 2-hydroxy-n,n-dimethyl-3-[[2-[[1(r)-(5-methyl-2-furanyl)propyl]amino]-3,4-dioxo-1-cyclobuten-1-yl]amino]benzamide

Disclosed is a process for making the compound of formula I: using the compounds of formulas II, Q, and XI or XII: wherein A is selected from the group consisting of Br, Cl and I (with Br being preferred); and R represents (C&#x2013;C)alkyl. Also disclosed are intermediate compounds that are made in the disclosed process.

Synthesis of 2-hydroxy-N,N-dimethyl-3-[ [2-[1 (R)-(5-methyl-2-furanyl)propyl]amino]-3,4-dioxo-1-cyclobuten-1-yl]aminobenzamide

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Plainsboro, NJ, United States of America

Jianguo Yin