反应详情

Under a nitrogen atmosphere, 2,6,7-trimethyl-4-phenoxy-1-[2-(3-pyridin-3-ylpropoxy)ethyl]-1H-imidazo[4,5-c]pyridine (4 g) from Part D and ammonium acetate (40 g) were heated in a sealed tube to 150° C. After 46.5 hours, NMR analysis indicated that only 7% of the starting material remained. The reaction mixture was cooled to ambient temperature, diluted with ethyl acetate, and washed 3 times with 1N potassium hydroxide and once with water. The organic layers were dried with magnesium sulfate and concentrated under reduced pressure. The resulting oil was triturated with 90/10 diethyl ether/toluene and the filtered solids were dried under vacuum at 45° C. The pale yellow solid was dissolved in 10% hydrochloric acid and extracted 3 times with dichloromethane (DCM). Potassium hydroxide was added to the aqueous layer to bring the pH to 14, and this was subsequently washed 3 times with DCM. The combined organic layers were washed once with water, 3 times with brine, dried with magnesium sulfate, and concentrated under reduced pressure. The oil was purified by column chromatography over silica using 97/3 DCM/methanol as the eluant. The oil was then triturated with diethyl ether/toluene and the resulting solid was recrystallized from ethyl acetate/hexane to yield 2,6,7-trimethyl-1-[2-(3-pyridin-3-ylpropoxy)ethyl]-1H-imidazo[4,5-c]pyridin-4-amine, m.p. 108.6–109.5° C.

1. washwashed 3 times with 1N potassium hydroxide
2. dry with materialThe organic layers were dried with magnesium sulfate
3. concentrationconcentrated under reduced pressure
4. customThe resulting oil was triturated with 90/10 diethyl ether/toluene
5. customthe filtered solids were dried under vacuum at 45° C
6. dissolutionThe pale yellow solid was dissolved in 10% hydrochloric acid
7. extractionextracted 3 times with dichloromethane (DCM)
8. additionPotassium hydroxide was added to the aqueous layer
9. washthis was subsequently washed 3 times with DCM
10. washThe combined organic layers were washed once with water, 3 times with brine
11. dry with materialdried with magnesium sulfate
12. concentrationconcentrated under reduced pressure
13. customThe oil was purified by column chromatography over silica using 97/3 DCM/methanol as the eluant
14. customThe oil was then triturated with diethyl ether/toluene
15. customthe resulting solid was recrystallized from ethyl acetate/hexane