تفاعل #169073

معادلة التفاعل

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

المردود 65.3%

المذيبات

dichloromethane

sodium bicarbonate

dichloromethane

ظروف التفاعل

المعالجة

1. 1
   أخرىThe layers were separated
2. 2
   غسيلThe organic layer was washed sequentially with water (×2) and brine
3. 3
   تجفيفdried over sodium sulfate
4. 4
   ترشيحfiltered
5. 5
   تركيزconcentrated under reduced pressure
6. 6
   أخرىThe 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
   درجة الحرارةin refluxing propyl acetate (80 mL) with the aid of methanol
9. 9
   درجة الحرارةto slowly cool
10. 10
    أخرىThe resulting precipitate was isolated by filtration
11. 11
    غسيلrinsed with cold propyl acetate
12. 12
    أخرىdried under high vacuum at 70° C.

الإجراء التجريبي

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.

المصدر