Synthesis
Step 87a: Synthesis of tert-butyl 5-bromo-1H-benzo[d]imidazole-1-carboxylate (compound 0601-187)
To a solution of 4-bromo-1,2-benzenediamine (3 g, 16 mmol) in N,N-dimethylformamide (DMF, 22 mL) was added trimethyl orthoformate (44 mL), which was subsequently concentrated. Concentrated hydrochloric acid (1.5 mL) was added and the reaction mixture was stirred at room temperature for 1 hour. Upon completion of the reaction, the mixture was diluted with deionized water (200 mL) and the pH was adjusted to 7 with saturated aqueous sodium bicarbonate. the reaction mixture was extracted with ethyl acetate (200 mL) and the organic layer was dried with anhydrous sodium sulfate and concentrated under reduced pressure to give 5-bromo-1H-benzo[d]imidazole (3.25 g, 100%) as an off-white solid. lc-MS (mass spectrum): m/z 197 [M + H]+. 1H NMR (400 MHz, DMSO-d6) δ 7.33 (t, J = 8.8 Hz, 1H), 7.55 (dd, J1 = 7.6 Hz, J2 = 40 Hz, 1H), 7.79 (d, J = 47.2 Hz, 1H), 8.26 (s, 1H), 12.61 (d, J = 25.6 Hz, 1H ).
References
[1] Patent: WO2011/130628, 2011, A1. Location in patent: Page/Page column 228
[2] Patent: US2013/102595, 2013, A1. Location in patent: Paragraph 0580; 0581
[3] Patent: JP2015/187145, 2015, A. Location in patent: Paragraph 0493
[4] Patent: US2009/326029, 2009, A1. Location in patent: Page/Page column 33
