Asymmetric Synthesis of 2-Phenylpyrrolidines for SAR Study of Thienopyrimidine-based EGFR Kinase Inhibitors

Abstract

The aim of this master s thesis was to carry out a preliminary structure-activity relationship (SAR) study of thieno[2,3-d]pyrimidines with racemic and enantioenriched 2-phenylpyrrolidine as a substituent on C-4. One objective was to investigate if secondary amines are essential substituents at C-4 by preparing thieno[2,3-d]pyrimidines with a tertiary heterocyclic amine. This study has also included compounds with pyrrolidine as a C-4 substituent, to study the contribution of the phenyl moiety on the amine on the EGFR-TK activity. All amines and thieno[2,3-d]pyrimidines have been synthesized as part of the project, and a second objective of this master s thesis was to investigate viable synthetic routes to obtain enantioenriched 2-phenylpyrrolidine with high chemical and enantiopurity.