Genentech, Inc.

Lexicon Pharmaceuticals, Inc.

Hoffmann-la Roche Inc.

F. Hoffmann-la Roche Ag

Lexicon Pharmaceutical Inc.

Haiming Zhang

Francis Gosselin

Wenxue Wu

Ngiap-Kie Lim

Stephan Bachmann

Ramanaiah C Kanamarlapudi

Jie Yan

Jie Xu

Hans Iding

Hugh Alfred Burgoon, Jr

Alec Fettes

Zhi-Cai Shi

Matthew Mangzhu Zhao

Mark S Bednarz

Shinya Iimura

Qiuling Song

Nicholas Andrew White

Kyle Bradley Pascual Clagg

Jing Li

Yang Zhang

Wei Gu

Sushant Malhotra

Chong Han

Jeffrey Stults

Qingping Tian

Susan Margaret De Paul

Xin Linghu

Andrew McClory

Iain Fraser Pickersgill

Theresa Cravillion

Youchu Wang

Patrik Meier

Danial Beaudry

Sebastian Herold

Alexander Gmehling

Chunbo Sha

Jianqian Zhang

Jinguang Lin

Alexandra Chestakova

Michael Dalziel

Ross Mabon

Bryce Alden Harrison

Nicole Cathleen Goodwin

Karthik Nagapudi

Roland Meier

Anett Perlberg

Paroma Chakravarty

Remy Angelaud

Alfred Stutz

Georg Wuitschik

Sarah Robinson

Tobias Bruetsch

William Nack

Jacob C Timmerman

Johannes Adrian Burkhard

Etienne Trachsel

Paul D O'Shea

Ugo Jonathan Orcel

Jeff Shen

Lauren Elizabeth Sirois

Cheol Keun Chung

Kyle Clagg

Qun Li

Stefan Hildbrand

Scott J Savage

Ying Wang

Ashok R Tunoori

Qingyun Liu

Haihong Jin

Brett A Marinelli

Chengmin Zhang

Serena Maria Fantasia

Arokiasamy Devasagayaraj

Stefan Koenig

Sean M Kelly

Andreas Stumpf

Pankaj Rege

Lakshama Samala

Theresa Humphries

Christian Moessner

Yonghui Ge

Johannes Burkhard

Antonio Giovanni Dipasquale

Rene Lebl

Joerg Sedelmeier

Thomas Michael Bass

Dainis Kaldre

Christian Leitner

Ngiap Kie Lim

Eduardo V Mercado-marin

Daniel Zell

Diane E Carrera

Raphael Bigler

Laure Elizabeth Simone Finet

Jie Zhang

Yuki Nakagawa

Regis Jean Georges Mondiere

Provided herein are processes for the preparation of substituted 1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indoles using Wenker-Synthesis towards the synthesis of GDC-9545.

Processes for the preparation of substituted 1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indoles

Provided herein are methods of synthesizing quinazoline compounds comprising at least one atropisomeric center.

Synthesis of quinazoline compounds

Provided herein are methods to synthesize compounds useful in the treatment of cancer where such compounds comprise a quinazolinyl core moiety and at least one stereoisomeric or atropisomeric moiety.

Process for synthesis of quinazoline compounds

A manufacturing process to a bis-mesylate salt 1b of the pan-RAF inhibitor 4-amino-n-(1-((3-chloro-2-fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide. The process features a number of efficient key reactions, including a robust and scalable Pd-catalyzed carbonylation reaction to generate thienopyrimidine 2 and a highly chemoselective Pt/V/C-catalyzed nitro group reduction to access penultimate intermediate 7. The final amide coupling of 7 and 2 was accomplished by a mild and safe protocol employing N,N,N',N′-tetramethylchloroformamidinium hexafluorophosphate (TCFH) as the coupling reagent, to produce a 1:1 adduct of the freebase and THF. The adduct afforded compound 1b with excellent yield, purity, and form stability on a multikilogram production scale after reaction with MsOH and recrystallization. The methods are able to produce a compound having upwards of 95% purity.

Synthesis of a bis-mesylate salt of 4-amino-N-(1-((3-chloro-2-fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide and intermediates thereto

Provided herein are processes for the preparation of indolyl intermediates using Wenker Synthesis for the total synthesis of SERD compounds useful in the treatment of cancer.

Processes for synthesis of substituted indole intermediates for the synthesis of serd compounds

Provided herein are solid forms, salts, and formulations of 3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropyl)azetidin-3-yl)amino)phenyl)-3-methyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indol-2-yl)-2,2-difluoropropan-1-ol, processes and synthesis thereof, and methods of their use in the treatment of cancer.

Solid forms of 3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropyl)azetidin-3- yl)amino)phenyl)-3-methyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indol-2-yl)-2,2-difluoropropan-1-ol and processes for preparing fused tricyclic compounds comprising a substituted phenyl or pyridinyl moiety, including methods of their use

Methods for preparing the Bruton's Tyrosine Kinase ('BTK') inhibitor compound 2-{3'-hydroxymethyl-1-methyl-5-[5-((S)-2-methyl-4-oxetan-3-yl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-[3,4&#x2032;]bipyridinyl-2&#x2032;-yl}-7,7-dimethyl-3,4,7,8-tetrahydro-2H,6H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one are provided. Methods for preparing tricyclic lactam compounds are also provided.

Process for preparing BTK inhibitors

A method of regio-selectively synthesizing an imidazo-pyrimidine compound of formulae (XXa) or (XXb) comprising a step of coupling a first compound of formula XX-P1a or XX-P1b with a second compound of formula XX-P2  This annulation reaction between &#x3b2;-ethoxy acrylamides and phosphorylated aminoimidazoles to furnish imidazo[1,2-a]pyrimidin-amines relies on steering effects from endocyclic and exocyclic phosphorylated aminoimidazoles. The reaction furnishes either 2-amino or 4-amino constitutional isomers of imidazo[1,2-a]pyrimidines with good yields and ranges of 90:10-99:1 regio-selectivity. The reaction is useful in the synthesis of various tracer molecules used in the study of neurological conditions such as where Rand Rtogether with the imidazole ring atoms to which they are bonded form a phenyl ring and the products are substituted benzimidazopyrimidines. The reaction can be generalized to form imidazo[1,2-a]pyrimidines substituted at either of their 2- and 4-positions by alkoxy or thioalkyl groups.

Regio-selective synthesis of imidazo[1,2-a]pyrimidines

A method of synthesizing comprising a step of making an imidazo-pyrimidine compound by coupling a first compound of formula (II) with a second compound of formula (III)  Followed by a deprotection and tosylation step. The methods are able to produce an isotopically substituted molecule having upwards of 95% purity relative to non-isotopically substituted molecules. The invention further comprises compounds of formula: 

Synthesis of labeled imidazo[1,2-A]pyrimidines

The present invention provides a process for the manufacture of a compound of formula VIIIa and salts forms of VIIIa where Ris an aryl sulfonic acid 

Process for the manufacturing of medicaments

Solid forms of 3-((1R,3R)-1-(2,6-difluoro-4-((1-(3- fluoropropyl)azetidin-3-yl)amino)phenyl)-3-methyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indol-2-yl)-2,2-difluoropropan-1-ol and processes for preparing fused tricyclic compounds comprising a substituted phenyl or pyridinyl moiety, including methods of their use

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Pennington, NJ, United States of America

Haiming Zhang