Schering Corporation

Merck Sharp + Dohme Corp.

Agnes S Kim-Meade

Xiaoyong Fu

Timothy L McAllister

Jianguo Yin

Shuyi Zhang

Jason L Winters

Anantha R Sudhakar

Doris P Schumacher

George G Wu

Frank Xing Chen

Arthur G Taveras

Michael P Dwyer

Younong Yu

Tiruvettipuram K Thiruvengadam

Shen-Chun Kuo

Marc Poirier

Kevin Joseph Klopfer

Yee-Shing Wong

Nanfei Zou

Donald Hou

Jeffrey Manning Eckert

Feng Liang

Kenneth Stanley Matthews

Mengwei Hu

Mathew Thomas Maust

Gerald Werne

Charles F Bernard

Frank Bruno Guenter

Timothy Mcallister

Jeffrey M Eckert

Yianguo Yin

Timothy L Macallister

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

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

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

An enantioselective process for preparing intermediates useful in the preparation of the chiral tricyclic compound of formula I is disclosed.

Enantioselective process

Disclosed is a process for preparing a compound of the formula:

Enantioselective alkylation of tricyclic compounds

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Fanwood, NJ, United States of America

Agnes S Kim-Meade