Thiophene skeleton exists in ticlopidine， olmutinib and tinoridine drugs， they can be used as antithrombotic drugs， antitumor drugs， anti-inflammatory analgesics. At present， the study on the modification of skeleton molecules of these compounds is one of the researched hotspots of pharmaceutical synthesis. In this paper， a novel synthetic method of polysubstituted thiophene derivative by one-pot multi-component reaction was reported. In the presence of K2CO3， 1,3-dicarbonyl compounds reacted with carbon disulfide， bromoethane and bromoacetonitrile. Their compositions and structures were characterized by nuclear magnetic resonance（1H NMR， 13C NMR） and high resolution mass spectrometer（HRMS）. The mechanism for the reaction was proposed. The method had the advantages of mild conditions， safe operation and higher yields.