Synthesis of 4‐substituted 2‐(4‐methylpiperazino)pyrimidines and quinazoline analogs as serotonin 5‐HT2A receptor ligands

The addition reaction of lithium reagents to the 4 position of 2-chloropyrimidine or 2-chloroquinazoline followed by oxidation of the resultant dihydro intermediate product is a powerful tool for the synthesis of 4-substituted 2-chloropyrimidines or 2-chloroquinazolines. 4-Vinyl derivatives undergo a conjugate nucleophilic addition across the vinyl group. A nucleophilic displacement of chloride in 4substituted 2-chloropyrimidines or 2-chloroquinazolines by treatment with 4-methylpiperazine provides compounds that are antagonists of the serotonin 5-HT2A receptor.