Process Development and Manufacture of the Core Starting Material of Adagrasib (MRTX849)

20 December 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

The beta-ketoester 1 is one of the critical starting materials used in the second-generation synthesis of adagrasib. Disclosed within is a new, streamlined, operationally simple and more environmentally friendly three-step telescoped protocol which was demonstrated on a >100 kg batch with an overall yield of 70%. Identification of the shortcomings and the quality issues of the initial route are discussed. The process development work overcoming these challenges and leading to the new route of synthesis is described.

Keywords

MRTX849
adagrasib
beta-ketoester
oncology
Dieckmann condensation

Supplementary materials

Title
Description
Actions
Title
Additional experiments and NMR spectra
Description
General experimental details, experiments with formaldehyde, reprocessing experiments, inorganic base screening, X-Ray data, characterization data and NMR spectra.
Actions

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.