4,6-dichloro-1-Methyl-1H-iMidazo[4,5-c]pyridine

Synthesis

General procedure for the synthesis of 4,6-dichloro-1-methyl-1H-imidazo[4,5-c]pyridin-7-amine from 4,6-dichloro-1-methyl-1H-imidazo[4,5-c]pyridine: a solution of sodium nitrite (5.28 g, 76.5 mmol) in water (17 mL) was added dropwise over 5 min to a stirred 4,6-dichloro-1-methyl-1H-imidazo and [4,5-c]pyridin-7-amine (11.3 g, 52 mmol) solution of hypophosphorous acid (50 wt.% aqueous solution, 150 mL), keeping the reaction temperature between 0°C and 50°C. The reaction mixture was gradually warmed to room temperature and stirring was continued for 40 minutes. Subsequently, the mixture was cooled in an ice bath to between 0 °C and 50 °C, and the pH was adjusted to >10 by addition of aqueous sodium hydroxide (55 g dissolved in 100 mL of water). the resulting suspension was filtered, and the filter cake was washed with water and dried by suction to afford the product 4,6-dichloro-1-methyl-1H-imidazo[4,5-c]pyridine (9.9 g, 97% yield), which was analyzed for purity by high performance liquid chromatography ( HPLC) analyzing the purity was 99%, retention time was 0.92 min, and the molecular ion peak (M+H)+ detected by LC/MS was 202.06 (204.04,206.02).

References

[1] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 10, p. 2646 - 2649
[2] Patent: WO2006/122137, 2006, A1. Location in patent: Page/Page column 71
[3] Patent: WO2006/53166, 2006, A1. Location in patent: Page/Page column 57