公开(公告)号：US20220227738A1

公开(公告)日：2022-07-21

申请号：US17612972

申请日：2020-05-20

Applicant: California Institute of Technology ,  1200 Pharma LLC ,  The Regents of the University of California

Inventor： Justin A. Hilf ,  Tristin E Rose ,  Michael D. Bartberger ,  Brendan M. O'Boyle ,  Corey M. Reeves ,  Oliver C. Loson ,  Brian M. Stoltz ,  Martina S. McDermott ,  Neil A. O'Brien ,  Dennis Slamon

IPC: C07D403/14 ,  C07D471/10 ,  C07D487/10 ,  C07D491/10 ,  C07D495/10 ,  C07D498/10

Abstract: The invention relates to compounds of Formula I, and pharmaceutically acceptable salts thereof, and methods of making and using the same. The compounds of the invention are effective in inhibiting KRAS protein with a G12C mutation and are suitable for use in methods of treating cancers mediated, in whole or in part, by KRAS G12C mutation.

公开(公告)号：US20220194949A1

公开(公告)日：2022-06-23

申请号：US17598152

申请日：2020-03-25

Applicant: California Institute of Technology ,  1200 Pharma LLC ,  The Regents of the University of California

Inventor： Brendan M. O'Boyle ,  Corey M. Reeves ,  Justin A. Hilf ,  Brian M. Stoltz ,  Michael D. Bartberger ,  Steven J. Wittenberger ,  Oliver C. Loson ,  Martina S. McDermott ,  Neil A. O'Brien ,  Dennis Slamon

IPC: C07D487/04 ,  A61P35/00

Abstract: The present disclosure describes compounds of formulas (I)-(V) and methods of making the same. The compounds of the present disclosure are useful as inhibitors of PRMT5 activity and in methods of treating cancers and other diseases.

公开(公告)号：US20220185828A1

公开(公告)日：2022-06-16

申请号：US17688122

申请日：2022-03-07

Applicant: California Institute of Technology

Inventor： Anton Toutov ,  Kerry Betz ,  Alexey Fedorov ,  Brian M. Stoltz ,  Wenbo Liu ,  Robert H. Grubbs

IPC: C07F7/08 ,  C07D209/12

Abstract: The present disclosure describes methods for silylating aromatic derivatives, comprising the use of hydrosilanes and potassium hydroxide.

公开(公告)号：US11124503B2

公开(公告)日：2021-09-21

申请号：US16055559

申请日：2018-08-06

Applicant: California Institute of Technology

Inventor： Brian M. Stoltz ,  Masaki Hayashi ,  Satoshi Hashimoto

IPC: C07D409/06 ,  C07D207/27 ,  C07D207/273 ,  C07D207/277

Abstract: This disclosure provides methods for intermolecular enantioselective C-acylation of lactams with quaternary stereogenic centers by applying a chiral Ni catalyst. The methods comprise treating a lactam of formula (IIa): with a chiral Ni catalyst, an aryl nitrile, and an aryl halide to provide compounds of formula (Ia):

公开(公告)号：US10919917B2

公开(公告)日：2021-02-16

申请号：US16705408

申请日：2019-12-06

Applicant: California Institute of Technology

Inventor： Anton Toutov ,  Kerry Betz ,  Alexey Fedorov ,  Brian M. Stoltz ,  Wenbo Liu ,  Robert H. Grubbs

IPC: C07F7/08 ,  C07D209/12

Abstract: The present disclosure describes methods for silylating heteroaromatic derivatives, comprising the use of hydrosilanes and potassium hydroxide.

公开(公告)号：US10906875B2

公开(公告)日：2021-02-02

申请号：US16427629

申请日：2019-05-31

Applicant: California Institute of Technology

Inventor： Brian M. Stoltz ,  Scott C. Virgil ,  David E. White ,  Taiga Yurino ,  Yiyang Liu ,  Douglas C. Behenna ,  Douglas Duquette ,  Christian Eidamshaus

IPC: C07D211/78 ,  C07D211/16 ,  C07D211/18 ,  C07D211/22 ,  C07D211/34 ,  C07D211/38 ,  C07D211/60 ,  C07D211/76 ,  C07D211/88 ,  C07D211/90 ,  C07D211/94 ,  C07D211/96 ,  C07D207/06 ,  C07D207/08 ,  C07D207/10 ,  C07D201/16 ,  C07D207/26 ,  C07D207/263 ,  C07D207/267 ,  C07D207/27 ,  C07D207/273 ,  C07D207/277 ,  C07D207/46 ,  C07D223/04 ,  C07D223/10 ,  C07D241/04 ,  C07D241/08 ,  C07D241/52 ,  C07D265/30 ,  C07D265/32 ,  C07D309/04 ,  C07D309/30 ,  C07D207/16

Abstract: The invention provides heterocyclic compounds with quaternary centers and methods of preparing compounds. Methods include the method for the preparation of a compound of Formula (II): comprising treating a compound of Formula (I): with a transition metal catalyst and under alkylation conditions as valence and stability permit.

公开(公告)号：US10513531B2

公开(公告)日：2019-12-24

申请号：US16159298

申请日：2018-10-12

Applicant: California Institute Of Technology

Inventor： Anton Toutov ,  Kerry Betz ,  Alexey Fedorov ,  Brian M. Stoltz ,  Wenbo Liu ,  Robert H. Grubbs

IPC: C07F7/08 ,  C07D209/12

Abstract: The present disclosure describes novel silylated heteroaromatic derivatives, including those prepared by methods comprising the use of hydrosilanes and at least one strong base, the definition of strong base now also including hydroxide, especially KOH.

公开(公告)号：US10421696B2

公开(公告)日：2019-09-24

申请号：US14972475

申请日：2015-12-17

Applicant: California Institute of Technology

Inventor： Brian M. Stoltz ,  Yoshitaka Numajiri ,  Beau P. Pritchett ,  Koji Chiyoda

IPC: C07B53/00 ,  C07D209/88 ,  C07D211/74 ,  C07D211/76 ,  C07D265/32 ,  C07C271/18 ,  C07C271/50 ,  C07C311/16 ,  C07C233/76

Abstract: This invention provides enantioenriched Mannich adducts with quaternary stereogenic centers and novel methods of preparing the compounds. Methods include the method for the preparation of a compound of formula (I): comprising treating a compound of formula (II): with a transition metal catalyst under alkylation conditions.

公开(公告)号：US20190055182A1

公开(公告)日：2019-02-21

申请号：US16166893

申请日：2018-10-22

Applicant: California Institute of Technology

Inventor： Brian M. Stoltz ,  Alexander N. Marziale ,  Robert A. Craig ,  Douglas Duquette ,  Kelly E. Kim ,  Marc Liniger ,  Yoshitaka Numajiri

IPC: C07C45/65 ,  C07D211/94 ,  C07D223/10 ,  B01J31/04 ,  C07D317/72 ,  C07C49/647 ,  C07C49/683

Abstract: This invention provides efficient and scalable enantioselective methods that yield 2-alkyl-2-allylcycloalkyanone compounds with quaternary stereogenic centers. Methods include the method for the preparation of a compound of formula (I): comprising treating a compound of formula (II) or (III): with a palladium (II) catalyst under alkylation conditions.

公开(公告)号：US10125153B2

公开(公告)日：2018-11-13

申请号：US15804275

申请日：2017-11-06

Applicant: CALIFORNIA INSTITUTE OF TECHNOLOGY

Inventor： Anton Toutov ,  Kerry Betz ,  Alexey Fedorov ,  Brian M. Stoltz ,  Wenbo Liu ,  Robert H. Grubbs

IPC: C08G75/00 ,  C07F7/08 ,  C07D209/12

Abstract: The present invention describes chemical systems and methods for silylating N—H bonds of aliphatic amines, said system or method comprising or consisting essentially of a mixture of (a) at least one organosilane and (b) at least one hydroxide, especially KOH, said system being preferably, but not necessarily substantially free of a transition-metal compound, and said methods comprising contacting a quantity of the organic substrate with a mixture of (a) at least one organosilane and (b) at least one strong base, under conditions sufficient to replace an N—H bond with a silyl N—Si bond.