반응 #169073

반응 방정식

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

수율 65.3%

용매

dichloromethane

sodium bicarbonate

dichloromethane

반응 조건

후처리

1. 1
   기타The layers were separated
2. 2
   세척The organic layer was washed sequentially with water (×2) and brine
3. 3
   건조dried over sodium sulfate
4. 4
   여과filtered
5. 5
   농축concentrated under reduced pressure
6. 6
   기타The 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
   온도in refluxing propyl acetate (80 mL) with the aid of methanol
9. 9
   온도to slowly cool
10. 10
    기타The resulting precipitate was isolated by filtration
11. 11
    세척rinsed with cold propyl acetate
12. 12
    기타dried under high vacuum at 70° C.

실험 절차

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.

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