Amgen Inc.

Andrew Thomas Parsons

Marc A Caporini

William Powazinik, Iv

Brian Mcneil Cochran

Kyle Quasdorf

Brian McNeil Cochran

Michael T Corbett

Matthew G Beaver

John T Colyer

Marc Anthony Caporini

Michal Achmatowicz

Joanna Robinson

Daniel J Griffin

Iv William Powazinik

John T Coyler

The present disclosure relates to an improved, efficient, scalable process to prepare intermediate compounds, such as 2,2′,2″-(1,3,5,2,4,6-trioxatriborinane-2,4,6-triyl)tris(3-fluorophenol), useful for the synthesis of compounds, such as Compound 9, for the treatment of KRAS G12C mutated cancers.

Synthesis of KRAS G12C inhibitor compound

Provided herein is a process for preparing compound A comprising (a) admixing 2-isopropyl-4-methylpyridin-3-amine (Compound B), or a salt thereof, a first base, and a reactive compound comprising phosgene or a phosgene equivalent in an organic solvent to form 3-isocyanato-2-isopropyl-4-methylpyridine (Compound C); (b) admixing Compound C and 2,6-dichloro-5-fluoronicotinamide (Compound D) to form 2,6-dichloro-5-fluoro-N-((2-isopropyl-4-methylpyridin-3-yl)carbamoyl)nicotinamide (Compound E); and (c) admixing Compound E and a second base to form a product mixture comprising Compound A and the second base. Also provided herein is a process for synthesizing AMG 510 comprising using Compound A prepared according to the disclosed processes

Process for preparing 7-chloro-6-fluoro-1-(2-isopropyl-4-methylpyridin-3-yl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

The present invention relates to an improved, efficient, scalable process to prepare intermediate compounds, such as compound 5M, having the structure useful for the synthesis of compounds that target KRAS G12C mutations, such as

Synthesis of key intermediate of KRAS G12C inhibitor compound

The present invention relates to an improved, efficient, scalable process to prepare intermediate compounds, such as compound 5M, having the structure useful for the synthesis of compounds that target KRAS G12C mutations, such as 

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Cambridge, MA, United States of America

Andrew Thomas Parsons