反应详情

Nicotinic acid (11.4 mg, 92.3 μmol) was combined with DMF (1.0 mL) to give a colorless solution. To this solution was added TBTU (29.6 mg, 92.3 μmol), and DIEA (54.2 mg, 71.8 μl) were added. Finally 1-(2-(2-aminoethoxy)-2-methylpropyl)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-4-amine (30 mg, 83.9 μmol) was added and the reaction mixture was stirred for 1 hour at room temperature. Volatiles were removed in high vacuum at 40° C. The residue was dissolve in a mixture of ethyl acetate (5 mL) and methanol (0.5 mL). 1N sodium hydroxide solution (1.5 mL) was added and after a few minutes stirring the layers were separated. The aqueous layer was extracted with ethyl acetate. The organic phases were combined dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica gel-NH2, 0% to 10% methanol in DCM) to give the title product (33 mg, 85%) as white foam; LC-MS (UV peak area, ESI) 88%, 463.2459 (MH+).

1. customto give a colorless solution
2. additionwere added
3. customVolatiles were removed in high vacuum at 40° C
4. dissolutionThe residue was dissolve in a mixture of ethyl acetate (5 mL) and methanol (0.5 mL)
5. addition1N sodium hydroxide solution (1.5 mL) was added and after a few minutes
6. stirringstirring the layers
7. customwere separated
8. extractionThe aqueous layer was extracted with ethyl acetate
9. dry with materialThe organic phases were combined dried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customThe residue was purified by flash chromatography (silica gel-NH2, 0% to 10% methanol in DCM)