Reacción #169073

Ecuación de reacción

Triethylamine

cyclohexylcarbonyl chloride

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

cyclohexylcarbonyl chloride

→

N-[2-(4-amino-2-ethoxymethyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)-1,1-dimethylethyl]cyclohexanecarboxamide

Rendimiento 65.3%

Disolventes

dichloromethane

sodium bicarbonate

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe layers were separated
2. 2
   LavadoThe organic layer was washed sequentially with water (×2) and brine
3. 3
   Secadodried over sodium sulfate
4. 4
   Filtraciónfiltered
5. 5
   Concentraciónconcentrated under reduced pressure
6. 6
   OtroThe residue was purified by flash chromatography (4×13 cm silica gel column, eluting with 3% methanol in chloroform)
7. 7
   workup.DISSOLUTIONThe purified material was dissolved
8. 8
   Temperaturain refluxing propyl acetate (80 mL) with the aid of methanol
9. 9
   Temperaturato slowly cool
10. 10
    OtroThe resulting precipitate was isolated by filtration
11. 11
    Lavadorinsed with cold propyl acetate
12. 12
    Otrodried under high vacuum at 70° C.

Procedimiento

Under a nitrogen atmosphere, a solution of 1-(2-amino-2-methylpropyl)-2-ethoxymethyl-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine (1.552 g, 4.94 mmol) in dichloromethane (50 mL) was cooled to 0° C. Triethylamine (1.38 mL, 9.92 mmol) and cyclohexylcarbonyl chloride (661 μL, 4.94 mmol) were added sequentially. Two (2) days later the reaction mixture was cooled and additional cyclohexylcarbonyl chloride (40 μL) was added. The reaction mixture was stirred overnight and then diluted with saturated sodium bicarbonate and dichloromethane (50 mL). The layers were separated. The organic layer was washed sequentially with water (×2) and brine, dried over sodium sulfate, filtered, and then concentrated under reduced pressure. The residue was purified by flash chromatography (4×13 cm silica gel column, eluting with 3% methanol in chloroform). The purified material was dissolved in refluxing propyl acetate (80 mL) with the aid of methanol, the methanol was boiled off, and the solution was allowed to slowly cool. The resulting precipitate was isolated by filtration, rinsed with cold propyl acetate, and dried under high vacuum at 70° C. to provide 1.37 g of N-[2-(4-amino-2-ethoxymethyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)-1,1-dimethylethyl]cyclohexanecarboxamide as a colorless crystalline solid, mp 210-211° C. Anal. calcd for C23H32N6O2: % C, 65.07; % H, 7.60; % N, 19.80. Found: % C, 64.93; % H, 7.76; % N, 19.97.

Fuente