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：US10882864B2

公开(公告)日：2021-01-05

申请号：US16460889

申请日：2019-07-02

Applicant: Genentech, Inc.

Inventor： Danial Beaudry ,  Theresa Cravillion ,  Francis Gosselin ,  Ngiap-Kie Lim ,  Sushant Malhotra ,  Qingping Tian ,  Haiming Zhang ,  Alexander Gmehling ,  Alec Fettes ,  Stephan Bachmann

IPC: C07D487/04 ,  B01J31/24

Abstract: 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′]bipyridinyl-2′-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.

公开(公告)号：US20200369670A1

公开(公告)日：2020-11-26

申请号：US16869512

申请日：2020-05-07

Applicant: Genentech, Inc.

Inventor： Kyle Bradley Pascual Clagg ,  Nicholas Andrew White ,  Haiming Zhang ,  Francis Gosselin ,  William Nack ,  Paul D. O'Shea

IPC: C07D487/04 ,  C07F9/24

Abstract: 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 β-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 R3 and R4 together 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.

公开(公告)号：US12172982B2

公开(公告)日：2024-12-24

申请号：US17398345

申请日：2021-08-10

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

Inventor： Ngiap-Kie Lim ,  Jeff Shen ,  Lauren Elizabeth Sirois ,  Jacob C. Timmerman ,  Etienne Trachsel ,  Nicholas Andrew White ,  Jie Xu ,  Haiming Zhang ,  Stephan Bachmann ,  Raphael Bigler ,  Kyle Bradley Pascual Clagg ,  Antonio Giovanni Dipasquale ,  Francis Gosselin ,  Ugo Jonathan Orcel ,  Roland Christoph Meier

IPC: C07D401/04 ,  C07D401/14

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

公开(公告)号：US11325912B2

公开(公告)日：2022-05-10

申请号：US16869512

申请日：2020-05-07

Applicant: Genentech, Inc.

Inventor： Kyle Bradley Pascual Clagg ,  Nicholas Andrew White ,  Haiming Zhang ,  Francis Gosselin ,  William Nack ,  Paul D. O'Shea

IPC: C07D487/04 ,  C07F9/24

Abstract: 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 β-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 R3 and R4 together 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.

公开(公告)号：US11098028B2

公开(公告)日：2021-08-24

申请号：US16535752

申请日：2019-08-08

Applicant: Genentech, Inc.

Inventor： Jinguang Lin ,  Alexandra Chestakova ,  Wei Gu ,  Hans Iding ,  Jing Li ,  Xin Linghu ,  Patrik Meier ,  Chunbo Sha ,  Jeffrey Stults ,  Youchu Wang ,  Haiming Zhang ,  Jianqian Zhang ,  Tao Zhang

IPC: C07D401/14 ,  C07D401/04 ,  C12P17/16 ,  A61P35/00 ,  A61P25/00 ,  A61P29/00

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

公开(公告)号：US20180134685A1

公开(公告)日：2018-05-17

申请号：US15866899

申请日：2018-01-10

Applicant: Genentech, Inc.

Inventor： Jinguang Lin ,  Alexandra Chestakova ,  Wei Gu ,  Hans Iding ,  Jing Li ,  Xin Linghu ,  Patrik Meier ,  Chunbo Sha ,  Jeffrey Stults ,  Youchu Wang ,  Haiming Zhang ,  Jianqian Zhang ,  Tao Zhang

IPC: C07D401/14 ,  C07D401/04 ,  C12P17/16

CPC classification number: C07D401/14 ,  A61P25/00 ,  A61P29/00 ,  A61P35/00 ,  C07D401/04 ,  C12P17/165

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

公开(公告)号：US20170022183A1

公开(公告)日：2017-01-26

申请号：US15285781

申请日：2016-10-05

Applicant: Genentech, Inc.

Inventor： Jinguang Lin ,  Alexandra Chestakova ,  Wei Gu ,  Hans Iding ,  Jing Li ,  Xin Linghu ,  Patrik Meier ,  Chunbo Sha ,  Jeffrey Stults ,  Youchu Wang ,  Haiming Zhang ,  Jianqian Zhang ,  Tao Zhang

IPC: C07D401/14 ,  C12P17/16 ,  C07D401/04

CPC classification number: C07D401/14 ,  A61P25/00 ,  A61P29/00 ,  A61P35/00 ,  C07D401/04 ,  C12P17/165

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

Abstract translation: 本发明提供了制备式（Ⅷa）化合物和（Ⅷa）盐形式的方法，其中Rc是芳基磺酸。

公开(公告)号：US11661424B2

公开(公告)日：2023-05-30

申请号：US17102086

申请日：2020-11-23

Applicant: Genentech, Inc.

Inventor： Danial Beaudry ,  Theresa Cravillion ,  Francis Gosselin ,  Ngiap-Kie Lim ,  Sushant Malhotra ,  Qingping Tian ,  Haiming Zhang ,  Alexander Gmehling ,  Alec Fettes ,  Stephan Bachmann

IPC: C07D487/04 ,  B01J31/24

CPC classification number: C07D487/04 ,  B01J31/2409 ,  B01J31/2414 ,  B01J2231/40 ,  B01J2531/824 ,  C07B2200/09

Abstract: 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′]bipyridinyl-2′-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.

公开(公告)号：US11136330B2

公开(公告)日：2021-10-05

申请号：US16869475

申请日：2020-05-07

Applicant: Genentech, Inc.

Inventor： Kyle Bradley Pascual Clagg ,  Nicholas Andrew White ,  Haiming Zhang ,  Francis Gosselin ,  William Nack ,  Paul D. O'Shea

IPC: C07D487/04 ,  C07F9/24

Abstract: 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: