Synthesis
Example 66: General procedure for the synthesis of 5-chloro-1H-benzo[d]imidazol-2(3H)-ones from 4-chloro-1,2-benzenediamine and N,N'-carbonylbisimidazole
66A. 4-Chloro-1,2-benzenediamine (20 g, 140.27 mmol) was dissolved in tetrahydrofuran (THF, 250 mL), followed by batch addition of N,N'-carbonyl diimidazole (27.3 g, 168.32 mmol). The reaction mixture was stirred at 25 °C overnight. Upon completion of the reaction, the black reaction solution was evaporated to dryness, quenched with 2.0 N hydrochloric acid (100 mL) and filtered. The resulting solid was dissolved in methanol and purified by a 50 g SCX column to give 5-chloro-1H-benzo[d]imidazol-2(3H)-one (14.6 g, 61.7% yield) as a yellow solid. Mass spectrum (ESI+) m/z: [M+H]+ 169; HPLC retention time tR = 1.14 min; 1H NMR (399.902 MHz, DMSO-d6) δ 6.91 (1H, d), 6.97-6.94 (2H, m), 10.74 (2H, s).
References
[1] Journal of Medicinal Chemistry, 2006, vol. 49, # 12, p. 3719 - 3742
[2] Patent: WO2008/75109, 2008, A1. Location in patent: Page/Page column 167-168
[3] Journal of Heterocyclic Chemistry, 1965, vol. 2, p. 41,43
[4] Archiv der Pharmazie, 2000, vol. 333, # 5, p. 123 - 129
[5] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 3, p. 719 - 723
