反应详情

Acetyl isothiocyanate (1.755 mL, 19.97 mmol) was added to a heated (100° C. oil bath) solution of cis-4-(5-amino-2-(2-(piperidin-1-yl)ethoxy)pyridin-4-ylamino)-N-isopropylcyclohexanecarbox-amide (8.06 g, 19.97 mmol) in dioxane (100 mL). After 5 minutes, complete conversion to the thiourea intermediate was observed. The reaction was cooled to RT, and EDC (11.49 g, 59.9 mmol) and DIPEA (12.56 mL, 71.9 mmol) were added. Heating was resumed at 60° C. for 2.5 hours. The reaction mixture was pre-absorbed onto silica gel, and purified via silica gel chromatography, eluting with 90:10:1 DCM:MeOH:NH4OH to yield cis-4-(2-acetamido-6-(2-(piperidin-1-yl)ethoxy)-1H-imidazo[4,5-c]pyridin-1-yl)-N-isopropylcyclohexanecarboxamide (8.56 g, 18.19 mmol, 91% yield) as an orange solid. MS m/z=471.2 [M+H], calc 470.61 for C25H38N6O3.

1. temperatureHeating
2. waitwas resumed at 60° C. for 2.5 hours
3. customThe reaction mixture was pre-absorbed onto silica gel
4. custompurified via silica gel chromatography
5. washeluting with 90:10:1 DCM