Infinity Pharmaceuticals, Inc.

Karyopharm Therapeutics Inc.

Eisai R&d Management Co., Ltd.

Infinity Discovery, Inc.

Brian C Austad

Michael J Grogan

Andre Lescarbeau

Somarajannair Janardanannair

Alfredo C Castro

Martin R Tremblay

Mark L Behnke

David Gregory Roe

Stephane Peluso

Francis Gerard Fang

Louis Grenier

Charles E Chase

Andre B Charette

Lin-Chen Yu

James I Wright

Edward Holson

James R Porter

Daniel G Genov

Roger H Pak

Brian H White

John J Lee

Priscilla L White

Tao Liu

Gregg F Keaney

Bryan Matthew Lewis

Marc Pesant

Theodore A Martinot

Adilah Bahadoor

Charles William Johannes

Trevor Lee Calkins

Jitendra D Belani

Sheldon L Wallerstein

Yongbo Hu

William J Christ

Silvio A Campagna

Farid Benayoud

Matthew Schnaderbeck

Xiaojie Zhu

André B Charette

Gordon Wilkie

Ching Kam Lo

William Christ

The present invention provides an improved process for preparation of the (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid (referred to as compound of the structural formula (III)), which is a useful key intermediate for the synthesis of Selinexor ((Z)-3-(3-(3,5-Bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N-(pyrazin-2-yl)acrylohydrazide). The process comprises reaction of the compound of the structural formula (I) (as described herein) with the compound of the structural formula (II) (as described herein) in the presence of a catalyst, an organic base and an ether-containing solvent. The subsequent hydrolysis of the formed compound of the structural formula (IIIa) (as described herein) is performed without isolation of the compound of the structural formula (IIIa), providing compound of the structural formula (III) in high yield and stereoselectivity.

Process for preparing XPO1 inhibitors and intermediates for use in the preparation of XPO1 inhibitors

The present invention relates to crystalline forms of the compound represented by Structural Formula I, and compositions comprising crystalline forms of the compound represented by Structural Formula I described herein. The crystalline forms of the compound of Structural Formula I and compositions comprising the crystalline forms of the compound of Structural Formula I provided herein, in particular, single crystalline Form A, can be incorporated into pharmaceutical compositions, which can be used to treat various disorders associated with CRM1 activity, including cancer. Also described herein are methods for preparing the compound of Structural Formula I and its single crystalline forms.

Polymorphs of Selinexor

Polymorphs of selinexor

The invention provides derivatives of cyclopamine having the following formula: 

Cyclopamine analogs

Intermediates and methods of their use in the synthesis of analogs of halichondrin B are provided.

Intermediates for the preparation of analogs of halichondrin B

The present invention provides macrocyclic compounds, synthesis of the same and intermediates thereto. Such compounds, and compositions thereof, are useful for treating or preventing proliferative disorders Formula (F-4).

Intermediates for the preparation of analogs of Halichondrin B

The present invention provides fatty acid amide hydrolase inhibitors, solid forms thereof, compositions thereof, and methods of making and using the same.

Methods of treating a fatty acid amide hydrolase-mediated condition

The invention relates to the preparation of amino-cyclopamines by the enzymatic transamination of a corresponding keto-cyclopamines in the presence of a cofactor and an amino donor.

Enzymatic transamination of cyclopamine analogs

Provided herein is a process for the transfer-hydrogenation of ketone analogs of members of the jervine type ofalkaloids, such as cyclopamine. Also provided herein are novel ruthenium transfer-hydrogenation catalysts.

Transfer hydrogenation of cyclopamine analogs

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Tewksbury, MA, United States of America

Brian C Austad