Synthesis of Atropisomeric Quinazolin-4-one Derivatives Based on Remote H/D and 12C/13C Discrimination

Abstract

Both enantiomers of 2-ethylquinazolin-4-ones bearing ortho-CH₃O/CD₃O and CH₃O/¹³CH₃O phenyl groups at the N3 position were prepared. These are isotopic atropisomeric compounds based on a remote and conformationally flexible H/D and ¹²C/¹³C discrimination, and it was found that a CHCl₃ solution of ortho-CH₃O/CD₃O derivative shows a slight specific optical rotation. Furthermore, diastereomeric quinazolinone derivatives bearing a chiral carbon were prepared, and their stereochemical purities and rotational stability as well as the isotopic atropisomerism were verified by ¹H NMR and chiral high-performance liquid chromatography (HPLC) analyses.