Solvothermal synthesis of multiple dihydropyrimidinones at a time has been developed in inexpensive and green bio-based solvent lactic acid without any additional catalysts or additives. By this method, thirty new dihydropyrimidinone derivatives were synthesized in two batches and characterized. All of the compounds were screened by Eg5 motor protein ATPase assay, and the positive compounds were tested against the Caco-2 cell line, HeLa cell line, L929 cell line and T24 cell line in vitro. Among them, compound C9 exhibited the best inhibitory activity against motor protein ATPase with an IC50 value of 30.25 μM and significant cytotoxic activity in the micromolar range against the cells above. The Lineweaver–Burk plot revealed that compound C9 was a mixed-type Eg5 inhibitor. A molecular modeling study using the Discovery Studio program was performed, where compound C9 exhibited good binding interaction with Eg5 motor protein ATPase, and this was consistent with the attained experimental results.

A green method called “one‐pot batch synthesis” has been developed for the simultaneous synthesis of two different types of heterocyclic derivatives, oxazolo [3, 2‐c] pyrimidines and hydroxyl ethyl dihydropyrimidones. The reaction was conducted under ultrasonic irradiation in green bio‐based solvent lactic acid without any additional catalysts and additives. From β‐hydroxyethyl urea, acetoacetyl esters/amines and aromatic aldehydes, fifteen oxazolopyrimidine and eleven hydroxyl ethyl dihydropyrimidones were synthesized using the method for the first time. The generation mechanism of two different kinds of products under ultrasonic irradiation from the same reaction conditions was explained by Density Functional Theory. All products were obtained in high yields and characterized by IR, NMR, ESI MS, and X‐ray diffraction.

An efficient solvothermal method for one pot batch simultaneous synthesis of oxazolopyrimidines and dihydropyrimidinones has been developed in a small amount of lactic acid without any additional catalysts and additives for the first time. Ten oxazolopyrimidines and nine novel dihydropyrimidinones were simultaneously synthesized by the condensation of 1, 3‐dicarbonyl compounds, aromatic aldehydes and β‐hydroxyethylurea in the solvothermal reactors. All products were obtained in high yields and characterized by IR, 1H NMR, 13C NMR, and HR‐MS. Further, the structure of oxazolopyrimidine has been undoubtedly identified with the means of single crystal X‐ray diffraction.