¹Department of Pharmaceutical Chemistry and PG Studies, Pd. Dr. Vithalrao Vikhe Patil Foundation’s College of Pharmacy, Post MIDC, Vilad Ghat, Ahmednagar 414111, (Maharashtra), India DOI : 10.12991/mpj.2014187237 A series of twenty two compounds containing thiazolo[3,2-a] pyrimidine carboxamide nucleus was synthesized by using microwave. Substituted acetoacetanilide was condensed with thiourea and substituted benzaldehydes in the presence of p-toluenesulfonic acid as catalyst in ethanol to get 2-thioxo- 1,2,3,4-tetrahydropyrimidine carboxamide. In the second step, 1,2,3,4-tetrahydropyrimidine carboxamides were treated with chloroacetic acid, anhydrous sodium acetate and glacial acetic acid to yield the title compounds. The reaction progress and purity of the synthesized compounds were monitored by TLC using silica gel G and by determining their melting points. Structures of title compounds were confirmed by elemental analysis, IR, ¹H NMR and mass spectral data. The antipsychotic activity for title compounds was performed using albino mice by rotarod and tail suspension method. Compounds have shown antipsychotic activity comparable with the standard risperidone. The 2D, 3D QSAR and molecular docking studies were performed using VLife MDS 3.5 software. The molecular modelling studies reveals that more potent antipsychotics from this series can be generated by substituting electronegative group at para and meta position of N-phenyl ring and less bulky group at 5-phenyl ring of thiazolo[3,2-a]pyrimidine-6-carboxamide nucleus. Keywords : Ramesh Sawant