Synthesis
General procedure for the synthesis of 1,3-dihydro-1-(1-methylethynyl)-2H-benzimidazol-2-one from ethyl acetoacetate and o-phenylenediamine: 50 grams of o-phenylenediamine, 90 grams of ethyl acetoacetate, and 5 grams of sodium hydroxide were dissolved in 300 ml of o-xylene. The reaction was refluxed at 130°C for about 7 hours, during which time the water generated was removed by means of a water separator. Upon completion of the reaction, the reaction mixture was cooled to 80 °C and washed twice with 100 ml of water to remove water-soluble impurities. Subsequently, the mixture was cooled to 0 °C to allow the target product to precipitate as a white solid. The solid product was collected by filtration and dried to give 65 g of 1,3-dihydro-1-(1-methylethynyl)-2H-benzimidazol-2-one (DOM-2) in 94% yield.
References
[1] Patent: CN108129396, 2018, A. Location in patent: Paragraph 0022; 0023; 0033; 0034
[2] Bulletin des Societes Chimiques Belges, 1987, vol. 96, # 10, p. 787 - 792
[3] Patent: CN102816121, 2016, B. Location in patent: Paragraph 0022-0024
[4] Journal of Chemical Research - Part S, 1996, # 2, p. 92 - 93
[5] Russian Journal of Physical Chemistry A, 2015, vol. 89, # 5, p. 807 - 811
[6] Lo, H. Y., Nemoto, P. A., Kim, J. M., Hao, M.-H., Qian, K. C., Farrow, N. A., Albaugh, D. R., Fowler, D. M., Schneiderman, R. D., August, E. M., Martin, L., Hill-Drzewi, M., Pullen, S. S., Takahashi, H., & Lombaert, S. D. (2011). Benzimidazolone as potent chymase inhibitor: Modulation of reactive metabolite formation in the hydrophobic (P1) region. Bioorganic & Medicinal Chemistry Letters, 21(15), 4533–4539.
https://doi.org/10.1016/j.bmcl.2011.05.126
