6-Bromo-1-methyl-1H-benzo[d]imidazole

Synthesis

General procedure for the synthesis of 6-bromo-1-methyl-1H-benzo[d]imidazole from 4-bromo-2-methylaminoaniline and trimethyl orthoformate: Stannous chloride dihydrate (9.8 g, 43 mmol) was added batchwise to a solution of intermediate 2 (5 g, 21.6 mmol) in ethanol (200 ml), and the mixture was heated and refluxed for 4 h, then concentrated under reduced pressure. The residue was treated with water (200 ml) and 1N sodium hydroxide solution (100 ml). After extraction with dichloromethane, the organic phase was dried with anhydrous sodium sulfate and concentrated under reduced pressure. The residue was dissolved in toluene (50 ml), trimethyl orthoformate (2.6 ml, 24 mmol) and p-toluenesulfonic acid (0.2 g) were added, and the mixture was heated to reflux for 2 h and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluting with dichloromethane/methanol (95/5). 6-Bromo-1-methyl-1H-benzo[d]imidazole was obtained as a cream-colored powder (2.5 g, 54.74%); melting point 126-128 °C.

References

[1] Patent: WO2004/111036, 2004, A1. Location in patent: Page 21
[2] Patent: WO2004/111046, 2004, A2. Location in patent: Page/Page column 18-19
[3] Patent: WO2014/100734, 2014, A1. Location in patent: Paragraph 00320
[4] Patent: WO2015/200677, 2015, A2. Location in patent: Paragraph 00459; 00460