Solid-Phase Synthesis of 2-Aminopiperidine

Significance

A novel solid-phase protocol for the preparation of 2-amino-4-arylpyrimidines was developed. Biginelli three-component condensation of benzaldehyde, ethyl acetoacetate, and thiourea was carried out under microwave irradiation to give pyrimidine-2-thione 1 (65%). The pyrimidine unit was immobilized onto polymer support via S-alkyl­ation with chloromethyl polystyrene followed by oxidative aromatization. The S-alkyl linker unit was oxidized (compound 2) and the resulting anchoring alkyl sulfone group was substituted with piperidine under microwave conditions (100 °C, 10 min) to release 2-amino-4-phenylpiperidine 3.