Gilead Calistoga LLC

Acerta Pharma B.v.

Gilead Sciences, Inc.

Other

Jerry B Evarts

Duong D Tran

Keiko Sujino

Jennifer Anne Treiberg

Leena Patel

Stephane Perreault

Gary Bruce Phillips

Fritz Blatter

Fang Wang

Musong Kim

Tjeerd Barf

Ernest A Carra

Edwin Aret

Cecile Krejsa

Dragos Vizitiu

Stacy Bremner

Tim Ingallinera

Joshua A Kaplan

Bing Shi

Michael J Gerber

Lafe J Purvis, Ii

Barton W Phillips

Devan Naduthambi

Suet Chung Yeung

Kirk L Stevens

Joshua J Van Veldhuizen

Suzanne Buttar

Tracy Ehiwe

Angang Wang

Lucinda Victoria Jackson

Katie Grace Cooper

David Allen Short

Lai Chun Chan

Michael Joseph Lawler

Rustam Ferdinand Garrey

Kirsty Jane Millard

Alexander James Telford

Andrew John Phillips

Qiu Junying

Shaun Alan Hughes

Robert John Cox

Christopher Worrall

Arthur Yeung

Paul Allen Bethel

Michael David Golden

William John Watkins

Zhimin Du

Brian Lannutti

Allard Kaptein

Roger G Ulrich

Neill A Giese

Kamal Deep Puri

Joshua I Kaplan

Duong Tran

Peter Johannes Servaas Savio Van Eijk

Frank L M Vos

Mathilda Maria Henrica Verstappen

Eric Jurriën Zijp

Terry Podoll

Remy E J N Litjens

Joshua Kaplan

Lafe J Ii Purvis

Joshua Van Veldhuizen

Stephane Perrault

Ernest Carra

Michael Gerber

Lafe J Purvis

The present disclosure relates, in general, to improved processes for the preparation of 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)pyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl}-N-(pyridin-2-yl)-benzamide, particularly large-scale processes for manufacturing 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)pyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl}-N-(pyridin-2-yl)benzamide and intermediates used in such processes.

Processes for the preparation of 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)-pyrrolidin-2-yljimidazo[1,5-a]-pyrazin-1-yl}n-(pyridin-2-yl)-benzamide

Processes for the preparation of 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)-pyrrolidin-2-yl]imidazo[1,5-a]-pyrazin-1-yl}N-(pyridin-2-yl)-benzamide

In some embodiments, the invention relates to crystalline solid forms, including hydrates, polymorphs, and salt forms, of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide. In some embodiments, the invention relates to amorphous solid forms of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide. In some embodiments, the invention also relates to pharmaceutical compositions containing the solid forms, and methods for treating conditions or disorders by administering to a subject a pharmaceutical composition that includes the forms, including pharmaceutical compositions and methods for overcoming the effects of acid reducing agents.

Crystal forms of (s)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-n-(pyridin-2-yl)benzamide

Crystal forms of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide maleate

A process for the synthesis of quinazolinone containing compounds which may be useful for the treatment of cancer, is hereby disclosed. In addition, compound intermediates relating to these processes are also disclosed.

Process methods for phosphatidylinositol 3-kinase inhibitors

In some embodiments, the invention relates to the compounds of Formula (I) and (II) or a pharmaceutically acceptable salt thereof, or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, in some embodiments, the present invention relates to the compounds of Formula (I) and (II), pharmaceutical compositions thereof, and the use of the compounds and pharmaceutical compositions in the treatment of a hyperproliferative disorder, an inflammatory disorder, an immune disorder, or an autoimmune disorder.

Imidazopyrazine inhibitors of Bruton's tyrosine kinase

Polymorphs of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one, compositions thereof, methods for their preparation, and methods for their use are disclosed.

Polymorphic forms of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one

Pharmaceutical composition comprising a crystal form of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide for treating diffuse large B-cell lymphoma

Polymorphs of a hydrochloride salt of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one, compositions thereof, methods for their preparation, and methods for their use are disclosed. Solvent forms of a hydrochloride salt of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one, compositions thereof, methods for their preparation, and methods for their use are also disclosed.

Polymorphic forms of a hydrochloride salt of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one

The present application provides the compounds of formula (J), or pharmaceutically acceptable salts, isomers, tautomer, or a mixture thereof, wherein X, Y, Z, n, m', A&#x2032;, R, R, and Rare described herein. The compounds are inhibitors to the activities of phosphatidylinositol 3-kinase (PI3K) and are useful for treating conditions mediated by one or more PI3K isoforms. The present application further provides pharmaceutical compositions that include a compound of formula (I), or pharmaceutically acceptable salts, isomers, tautomer, or mixture thereof, and methods of using these compounds and compositions for treating conditions mediated by one or more PI3K isoforms.

Phosphatidylinositol 3-kinase inhibitors

The present application provides the compounds of formula (J), or pharmaceutically acceptable salts, isomers, or a mixture thereof, wherein n, m, q, A', W, W, W, R, R, and Rare described herein. The compounds are inhibitors to the activities of phosphatidylinositol 3-kinase (PI3K) and are useful for treating conditions mediated by one or more PI3K isoforms. The present application further provides pharmaceutical compositions that include a compound of formula (J), or pharmaceutically acceptable salts, isomers, tautomer, or mixture thereof, and methods of using these compounds and compositions for treating conditions mediated by one or more PI3K isoforms.

Pharmaceutical composition comprising a crystal form of (S)-4-(8-amino-3-(1-(but-2-ynoyl) pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide

A process for the synthesis of benzoxazinone containing compounds which may be useful precursors for synthesizing compounds for the treatment of cancer, is hereby disclosed.

Process for preparing phosphatidylinositol 3-kinase inhibitors and intermediates thereof

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Foster City, CA, United States of America

Jerry B Evarts