4-Toluenesulfonyl chloride → HCID 22100726, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-((N-(tert-butoxycarbonyl)piperidin-4-yl)amino)benzimidazole (1.50 g, 4.75 mmol) in DMF (30 mL) at 0° C. was added NaH (210 mg, 5.2 mmol). The solution was stirred for 0.5 hours when tosyl chloride (1.0 g, 5.2 mmol) was added. The reaction mixture was stirred for 1 hour at 0° C. when it was worked up with ethyl acetate and water, dried (MgSO4), and concentrated to an oil to afford 1-tosyl-5-((N-(tert-butoxycarbonyl)piperidin-4-yl)amino)benzimidazole and its regioisomer, 1-tosyl-6-((N-(tert-butoxycarbonyl)piperidin-4-yl)amino)benzimidazole. The resulting oil was taken up in DMF (30 mL) when it was charged with K2CO3 (4 g) and methyl iodide (3 mL). After 12 hours at ambient temperature, the reaction mixture was worked up with ethyl acetate and water, dried (MgSO4), and concentrated to an oil. The resulting tosylated product, 1-tosyl-5-((N-(tert-butoxycarbonyl)piperidin-4-yl)(methyl)amino)benzimidazole and the corresponding regioisomer, was taken up in methanol (80 mL) and NaOH (0.3 g, 7.5 mmol) was added. After 1 hour at ambient temperature, the methanol was removed in vacuo and the product recovered via chromatography on silica gel eluting with 5% to 10% methanol in methylene chloride to give 473 mg (30%) 5-((N-(tert-butoxycarbonyl)piperidin-4-yl)(methyl)amino)benzimidazole.

Provenance & Evidence