The invention relates to the technical field of compound preparation, in particular to a preparation method of 2, 4-dichlorothieno [3, 2, d]
pyrimidine, which comprises the following steps: S1, adding methyl 3-aminothiophene-2-
formate, water and glacial
acetic acid into a reaction kettle, dropwise adding a
potassium cyanate aqueous solution while stirring, and after dropwise adding, carrying out heat preservation reaction to obtain an intermediate I; s2, returning the intermediate I to a reaction kettle, adding water and a 30%
sodium hydroxide solution for reaction, acidifying, and performing suction
filtration to obtain an intermediate II; s3,
dichloromethane, the intermediate II, a
bismuth-based catalyst and diisopropylethylamine are added into the reaction kettle,
phosphorus oxychloride is dropwise added for a reaction, after the reaction is quenched, aftertreatment is conducted, and a target product is obtained. The 2, 4-dichlorothieno [3, 2, d]
pyrimidine prepared by the method has higher purity and yield, the reaction
controllability is enhanced by controlling the
reaction temperature, the dropping speed and the reaction time, and the
safety risk caused by too violent reaction or out-of-control reaction is reduced.