Millennium Pharmaceuticals Limited

Ian G Armitage

Steven P Langston

Quentin J McCubbin

Marianne Langston

Martin Ian Cooper

Lei Zhu

Eric L Elliott

Matthew Stirling

Stepan Vyskocil

Stephen William Watt

Mark D Eddleston

Reenu Chopra

Neil C Faiber

Hiro Mizutani

Hirotake Mizutani

Eric L Elliot

Quentin J Mccubbin

The present invention provides processes and synthetic intermediate (Ia) for the synthesis of 4-substituted ((1S, 2S, 4R)-2-hydroxy-4-{7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentyl)methyl sulfamates. These sulfamate compounds are E1 activating enzyme inhibitors, and are useful for the treatment of disorders of cell proliferation, particularly cancer, and other disorders associated with E1 activity. 

Process for the synthesis of E1 activating enzyme inhibitors

The present invention is directed to a compound of formula (I): or a crystalline form thereof, or a solvate thereof; to a solid pharmaceutical composition comprising a pharmaceutically effective amount of the compound of formula (I), or a crystalline form thereof, or a solvate thereof, and at least one pharmaceutically acceptable carrier or diluent, and to the use of a compound of formula (I), or a crystalline form thereof, or a solvate thereof, for treating a patient suffering from, or subject to, a disease, disorder, or condition mediated by Aurora kinase, and methods related thereto.

Crystalline forms of sodium 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido [5,4-D][2]benzazepin-2-YL]amino}-2-methoxybenzoate

Disclosed is a compound of formula (I): crystalline forms thereof, and solvates thereof; pharmaceutical compositions comprising a pharmaceutically effective amount of the compound of formula (I), or a crystalline form thereof, or a solvate thereof, and a pharmaceutically acceptable carrier or diluent; and the use of a compound of formula (I), or a crystalline form thereof, or a solvate thereof, for treating a patient suffering from, or subject to, a pathological condition capable of being ameliorated by inhibiting an E1 activating enzyme, particularly NAE, including, e.g., cancer.

Hydrochloride salt of((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-D]pyrimidin-7-YL}-2-hydroxycyclopentyl) methyl sulfamate

The present invention provides sulfamoylating reagents of formula RN&#x2014;S(O)X, wherein X is a cyclic tertiary amine or a nitrogen-containing heteroaryl and Ris an amine protecting group or hydrogen.

Sulfamoylating reagents

Hydrochloride salt of((1S,2S,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl sulfamate

Disclosed are processes and synthetic intermediates for the synthesis of compounds of formula (V) wherein the variables have the definitions contained herein. Such compounds are E1 activating enzyme inhibitors, and are useful for the treatment of disorders of cell proliferation, particularly cancer, and other disorders associated with E1 activity. 

Crystalline forms of sodium 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-D][2]benzazepin-2-yl]amino}-2-methoxybenzoate

Growing community of inventors

Stoneham, MA, United States of America

Ian G Armitage