公开(公告)号：US11999749B2

公开(公告)日：2024-06-04

申请号：US17852227

申请日：2022-06-28

Applicant: Genentech, Inc. ,  Hoffmann-La Roche Inc.

Inventor： Francis Gosselin ,  Stefan G. Koenig ,  Eduardo V. Mercado-Marin ,  Andreas Stumpf ,  Daniel Zell ,  Haiming Zhang ,  Stephan Bachmann ,  Diane E. Carrera ,  Michael E. Dalziel ,  Yonghui Ge ,  Jie Zhang ,  Raphael Bigler ,  Laure Elizabeth Simone Finet ,  Regis Jean Georges Mondiere ,  Yuki Nakagawa

IPC: C07D495/04

CPC classification number: C07D495/04

Abstract: 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.

公开(公告)号：US11643421B2

公开(公告)日：2023-05-09

申请号：US17115095

申请日：2020-12-08

Applicant: Genentech, Inc.

Inventor： Andreas Stumpf ,  Remy Angelaud ,  Andrew McClory ,  Herbert Yajima ,  Chudi Ndubaku ,  Alan Olivero

IPC: C07D498/14 ,  C07D487/04 ,  C07D498/22 ,  A61P35/00 ,  A61K9/00 ,  A61K31/495 ,  A61K31/5383 ,  A61K39/395 ,  A61K45/06

CPC classification number: C07D498/14 ,  A61K9/0053 ,  A61K31/495 ,  A61K31/5383 ,  A61K39/3955 ,  A61K45/06 ,  A61P35/00 ,  C07D487/04 ,  C07D498/22

Abstract: The present disclosure provides for methods for preparing tricyclic PI3K inhibitor compounds in high yield and purity in aqueous solvent systems.

公开(公告)号：US20210253599A1

公开(公告)日：2021-08-19

申请号：US17115095

申请日：2020-12-08

Applicant: Genentech, Inc.

Inventor： Andreas Stumpf ,  Remy Angelaud ,  Andrew McClory ,  Herbert Yajima ,  Chudi Ndubaku ,  Alan Olivero

IPC: C07D498/14 ,  C07D487/04 ,  C07D498/22 ,  A61P35/00 ,  A61K9/00 ,  A61K31/495 ,  A61K31/5383 ,  A61K39/395 ,  A61K45/06

Abstract: The present disclosure provides for methods for preparing tricyclic PI3K inhibitor compounds in high yield and purity in aqueous solvent systems.

公开(公告)号：US10906918B2

公开(公告)日：2021-02-02

申请号：US15780328

申请日：2016-12-16

Applicant: GENENTECH, INC.

Inventor： Andreas Stumpf ,  Remy Angelaud ,  Andrew McClory ,  Herbert Yajima ,  Chudi Ndubaku ,  Alan Olivero

IPC: C07D498/14 ,  C07D487/04 ,  C07D498/22 ,  A61P35/00 ,  A61K9/00 ,  A61K31/495 ,  A61K31/5383 ,  A61K39/395 ,  A61K45/06

Abstract: The present disclosure provides for methods for preparing tricyclic PI3K inhibitor compounds in high yield and purity in aqueous solvent systems.

公开(公告)号：US20230242550A1

公开(公告)日：2023-08-03

申请号：US18189623

申请日：2023-03-24

Applicant: Genentech, Inc.

Inventor： Andreas Stumpf ,  Remy Angelaud ,  Andrew McClory ,  Herbert Yajima ,  Chudi Ndubaku ,  Alan Olivero

IPC: C07D498/14 ,  C07D487/04 ,  C07D498/22 ,  A61P35/00 ,  A61K9/00 ,  A61K31/495 ,  A61K31/5383 ,  A61K39/395 ,  A61K45/06

CPC classification number: C07D498/14 ,  C07D487/04 ,  C07D498/22 ,  A61P35/00 ,  A61K9/0053 ,  A61K31/495 ,  A61K31/5383 ,  A61K39/3955 ,  A61K45/06

Abstract: The present disclosure provides for methods for preparing tricyclic PI3K inhibitor compounds in high yield and purity in aqueous solvent systems.

公开(公告)号：US20180354970A1

公开(公告)日：2018-12-13

申请号：US15780328

申请日：2016-12-16

Applicant: GENENTECH, INC.

Inventor： Andreas Stumpf ,  Remy Angelaud ,  Andrew McClory ,  Herbert Yajima ,  Chudi Ndubaku ,  Alan Olivero

IPC: C07D498/14 ,  A61P35/00 ,  A61K9/00 ,  A61K45/06 ,  A61K39/395 ,  A61K31/495 ,  A61K31/5383

CPC classification number: C07D498/14 ,  A61K9/0053 ,  A61K31/495 ,  A61K31/5383 ,  A61K39/3955 ,  A61K45/06 ,  A61P35/00 ,  C07D487/04 ,  C07D498/22

Abstract: The present disclosure provides for methods for preparing tricyclic PI3K inhibitor compounds in high yield and purity in aqueous solvent systems.