Kargbo RB.
Usona Institute, San Luis Obispo, USA
Improved Synthesis of New FDA-Approved Treatment for KRAS G12C Mutation in Non-small Cell Lung Cancer.
ACS Med. Chem. Lett. 2021;
12: 1186-1187
DOI:
10.1021/acsmedchemlett.1c00330
Key words
sotorasib - AMG 510 - Suzuki–Miyaura coupling - atropisomers
Significance
Sotorasib (AMG 510, Lumakras) is the first ever FDA-approved drug that inhibits KRAS, a cancer target that has been termed “undruggable” even after over 40 years of cancer research. It was approved for KRAS G12C-mutated non-small cell lung cancer (NSCLC).
Comment
Urea D cyclized to give rac-dione E as a mixture of atropisomers in 41% yield over three steps. Chiral separation via the (+)-2,3-dibenzoyl-d-tartrate salt of rac-dione E led to M-dione M-F in 37% yield over two steps. For experimental details, see: WO 2021 097207 A1 and WO 2020 232130 A1.
