Reacción #91973

Ecuación de reacción

1-(2-(2-aminoethoxy)-2-methylpropyl)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-4-amine

Nicotinic acid

TBTU

DIEA

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title product

Rendimiento 85.0%

N-(2-(1-(4-Amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-yloxy)ethyl)nicotinamide

Rendimiento 85.0%

Disolventes

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroto give a colorless solution
2. 2
   workup.ADDITIONwere added
3. 3
   OtroVolatiles were removed in high vacuum at 40° C
4. 4
   workup.DISSOLUTIONThe residue was dissolve in a mixture of ethyl acetate (5 mL) and methanol (0.5 mL)
5. 5
   workup.ADDITION1N sodium hydroxide solution (1.5 mL) was added and after a few minutes
6. 6
   workup.STIRRINGstirring the layers
7. 7
   Otrowere separated
8. 8
   ExtracciónThe aqueous layer was extracted with ethyl acetate
9. 9
   SecadoThe organic phases were combined dried over Na2SO4
10. 10
    Filtraciónfiltered
11. 11
    Concentraciónconcentrated in vacuo
12. 12
    OtroThe residue was purified by flash chromatography (silica gel-NH2, 0% to 10% methanol in DCM)

Procedimiento

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+).

Fuente