Acetic Acid → 5-Chloro-2,7-dimethyl-1H-imidazo[4,5-b]pyridine

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Reaction Conditions

Reaction Steps

2-Amino-6-chloro-4-methyl-3-nitropiridine (1.2 g, 6.40 mmol) synthesized according to the method described in WO98/02442 was dissolved in ethanol (65 mL), and tin(II) chloride dihydrate (4.33 g, 19.2 mmol) was added, followed by stirring at 75° C. for 2 hours. The reaction mixture was diluted with ethyl acetate and was added with 3 mol/L aqueous sodium hydroxide solution. The unsoluble material was filtered out through Celite, and washed with ethyl acetate. The filtrate was sequentially washed with water, saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Next, polyphosphoric acid (15.3 g) and acetic acid (1.72 mL, 30.0 mmol) was added to the residue, and was stirred for 80° C. for 3 hours. The reaction mixture was moved to ice water and sodium carbonate (11.4 g, 0.108 mol) was added in a little portion while stirring. Then, 28% aqueous ammonia solution was added to the residue to control the pH to 9 and the mixture was stirred for 1 hour. Precipitated crude crystals were collected by filtration, and were washed with water, and the obtained crystals were dried in vacuo at 40° C. overnight to obtain Compound P38 (395 mg, 34%).

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