公开(公告)号：US20230250074A1

公开(公告)日：2023-08-10

申请号：US18164302

申请日：2023-02-03

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

Inventor： Rene LEBL ,  Ngiap Kie LIM ,  Roland Christoph MEIER ,  Ugo Jonathan ORCEL ,  Joerg SEDELMEIER ,  Jeff SHEN ,  Lauren Elizabeth SIROIS ,  Jacob C. TIMMERMAN ,  Etienne TRACHSEL ,  Nicholas Andrew WHITE ,  Jie XU ,  Haiming ZHANG ,  Stephan BACHMANN ,  Thomas Michael BASS ,  Raphael BIGLER ,  Johannes Adrian BURKHARD ,  Kyle Bradley Pascual CLAGG ,  Francis GOSSELIN ,  Chong HAN ,  Dainis KALDRE ,  Sean M. KELLY ,  Sebastian HEROLD ,  Christian LEITNER

IPC: C07D401/04 ,  B01J23/44 ,  B01J23/755

CPC classification number: C07D401/04 ,  B01J23/44 ,  B01J23/755

Abstract: 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.

公开(公告)号：US20230028651A1

公开(公告)日：2023-01-26

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

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 PtN/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：US20250051351A1

公开(公告)日：2025-02-13

申请号：US18680689

申请日：2024-05-31

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

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 2and 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：US20240317738A1

公开(公告)日：2024-09-26

申请号：US18455783

申请日：2023-08-25

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

Inventor： Cheol Keun CHUNG ,  Jie XU ,  Hans IDING ,  Kyle CLAGG ,  Michael DALZIEL ,  Alec FETTES ,  Francis GOSSELIN ,  Ngiap-Kie LIM ,  Andrew MCCLORY ,  Haiming ZHANG ,  Paroma CHAKRAVARTY ,  Karthik NAGAPUDI ,  Sarah ROBINSON

IPC: C07D471/04 ,  C07D403/14

CPC classification number: C07D471/04 ,  C07D403/14 ,  C07B2200/13

Abstract: 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.

公开(公告)号：US20240294464A1

公开(公告)日：2024-09-05

申请号：US18642526

申请日：2024-04-22

Applicant: Genentech, Inc.

Inventor： Nicholas WONG ,  Francis GOSSELIN

IPC: C07C229/34 ,  A61K51/08 ,  A61K51/10 ,  C07C57/15 ,  C07C227/18 ,  C07C227/40 ,  C07D239/557 ,  C07D319/12 ,  C07F5/06

CPC classification number: C07C229/34 ,  A61K51/088 ,  A61K51/1096 ,  C07C57/15 ,  C07C227/18 ,  C07C227/40 ,  C07D239/557 ,  C07D319/12 ,  C07F5/069 ,  C07B2200/05

Abstract: Improved methods of synthesis of a restrained complexing agent are described herein. Compounds, including salts and solvates thereof, and compositions relevant to the improved methods are also described.

公开(公告)号：US20210079004A1

公开(公告)日：2021-03-18

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

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：US20200062762A1

公开(公告)日：2020-02-27

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：US20180230155A1

公开(公告)日：2018-08-16

申请号：US15841828

申请日：2017-12-14

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：US20160200723A1

公开(公告)日：2016-07-14

申请号：US14913635

申请日：2014-08-21

Applicant: GENENTECH, INC. ,  ARRAY BIOPHARMA INC.

Inventor： Chong HAN ,  Keena GREEN ,  Francis GOSSELIN ,  Michelangelo SCALONE ,  Paul J. NICHOLS ,  Weidong LIU ,  Keith L. SPENCER ,  Zackary D. CRANE ,  Peter J. STENGEL ,  Sagar SHAKYA

IPC: C07D471/04

CPC classification number: C07D471/04

Abstract: The invention provides processes of preparation thereof useful in the preparation of compounds that can be used as CHK1 inhibitors.

Abstract translation: 本发明提供了可用于制备可用作CHK1抑制剂的化合物的制备方法。