The starting materials 2-acetylnaphtho [2, 1-b] furan have been synthesized by literature (Stoermer and Schaffer) method. It is then converted in to a series of substituted chalcone 1a-e were prepared by Claisen -Schmidt condensation with substituted aromatic aldehydes. These chalcones on reaction with thiourea in presence of ethanol and concentrated hydrochloric acid gave their corresponding thiopyrimidine derivatives 2a-e, subsequent treatment with mono chloroacetic acid and anhydrous sodium acetate yields 5-(4-substitued aryl) -7 - (naphtho [2, 1-b] furan -2-yl) -2H – thiazole [3, 2-α ] pyrimidine -3(5H)-one derivatives 3a-e. The newly synthesized compounds are characterized by elemental analysis, spectral studies and have been evaluated for biological activity.