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：US10457648B2

公开(公告)日：2019-10-29

申请号：US15514188

申请日：2015-09-25

Applicant: F. HOFFMANN-LA ROCHE AG ,  GENENTECH, INC.

Inventor： Francis Gosselin ,  Chong Han ,  Hans Iding ,  Reinhard Reents ,  Scott Savage ,  Beat Wirz

IPC: C07D239/70 ,  C07D239/54 ,  C07D239/42 ,  C07C253/30 ,  C07C255/22 ,  C07B57/00 ,  C12P41/00 ,  C07C253/34 ,  C12N9/78

Abstract: The present disclosure relates to processes for preparing (cyclopentyl[d]pyrimidin-4-yl)piperazine compounds, and more particularly relates to processes for preparing (R)-4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d] pyrimidin-4-yl)piperazine and N-protected derivatives thereof, which may be used as an intermediate in the synthesis of Ipatasertib (i.e., (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(isopropylamino)-propan-1-one). The present disclosure additionally relates to various compounds that are intermediates employed in these processes.

公开(公告)号：US10435378B2

公开(公告)日：2019-10-08

申请号：US15827985

申请日：2017-11-30

Applicant: GENENTECH, INC.

Inventor： Hans Iding ,  Reinhard Reents ,  Michelangelo Scalone ,  Francis Gosselin

IPC: C12P9/00 ,  C07D239/70 ,  C07C269/06 ,  C07C271/22 ,  C12P17/16

Abstract: The present invention relates to a process for the preparation of a compound of formula (I) wherein R1 is as defined herein, which is useful as an intermediate in the preparation of active pharmaceutical compounds.

公开(公告)号：US09505725B2

公开(公告)日：2016-11-29

申请号：US15018636

申请日：2016-02-08

Applicant: Genentech, Inc.

Inventor： Paroma Chakravarty ,  Sanjeev Kothari ,  Francis Gosselin ,  Scott J. Savage ,  Jeffrey Stults

IPC: C07D239/70 ,  A61K31/496 ,  C07D403/04 ,  A61K31/517

CPC classification number: C07D239/70 ,  A61K31/517 ,  C07D403/04

Abstract: Disclosed is (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(isopropylamino)propan-1-one monohydrochloride, forms, formulations, pharmaceutical compositions, processes of manufacturing and methods of use thereof.

Abstract translation: 公开了（S）-2-（4-氯苯基）-1-（4 - （（5R，7R）-7-羟基-5-甲基-6,7-二氢-5H-环戊二烯并[d] 哌啶-1-基）-3-（异丙基氨基）丙-1-酮单盐酸盐，形式，制剂，药物组合物，制备方法及其使用方法。

公开(公告)号：US12071422B2

公开(公告)日：2024-08-27

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：US20240166595A1

公开(公告)日：2024-05-23

申请号：US18519529

申请日：2023-11-27

Applicant: Genentech, Inc.

Inventor： Rémy Angelaud ,  Tobias Bruetsch ,  Francis Gosselin ,  Chong Han ,  Alfred Stutz

IPC: C07C313/06 ,  B01J23/72 ,  C07C215/08 ,  C07D263/20 ,  C07D498/04 ,  C07F7/18

CPC classification number: C07C313/06 ,  B01J23/72 ,  C07C215/08 ,  C07D263/20 ,  C07D498/04 ,  C07F7/1892

Abstract: Methods of making benzoxazepin oxazolidinone compounds as well as synthetic intermediates are described, including compound (10-2) and compound 18:

公开(公告)号：US11780834B2

公开(公告)日：2023-10-10

申请号：US17110607

申请日：2020-12-03

Applicant: Hoffmann-La Roche Inc. ,  GENENTECH, 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：US11414412B2

公开(公告)日：2022-08-16

申请号：US17016900

申请日：2020-09-10

Applicant: Genentech, Inc.

Inventor： Francis Gosselin ,  Andrew McClory ,  Zhigang Cheng

IPC: C07D417/14

Abstract: A process for the manufacture N-(5-((5R,6S)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2,6-difluorophenyl)thiazole-4-carboxamide (I) wherein the vicinal amino fluoro substituents are introduced by treating 5 with sodium chloro((4-nitrophenyl)sulfonyl)amide and N-bromosucinimide and unraveling the resulting substituted aziridine (6) with trimethylamine trihydrofluoride to afford 7 which is further processed to afford 1.

公开(公告)号：US20220081413A1

公开(公告)日：2022-03-17

申请号：US17398345

申请日：2021-08-10

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

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

IPC: C07D401/14

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

公开(公告)号：US10954234B2

公开(公告)日：2021-03-23

申请号：US16443515

申请日：2019-06-17

Applicant: Genentech, Inc. ,  Hoffman-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 ,  A61P35/00 ,  A61P35/04

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.