反应详情

Triethylamine (556 μL, 4.00 mmol) and isobutyryl chloride (230 μL, 2.20 mmol) were added sequentially to a chilled (0° C.) solution of 1-(2-amino-2-methylpropyl)-2-ethoxymethyl-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine (628 mg, 2.00 mmol) in dichloromethane (20 mL). The reaction mixture was allowed to warm slowly to ambient temperature overnight. The reaction mixture was quenched with aqueous saturated sodium bicarbonate and diluted with dichloromethane (50 mL). The organic layer was separated, washed sequentially with water and brine, dried over sodium sulfate, filtered, and then concentrated under reduced pressure to an amber foam. This material was dissolved in hot propyl acetate (10 mL) and then allowed to cool overnight. Hexanes were added and the now cloudy solution was heated until clear and then allowed stand until crystals formed. The solvent was removed by pipette. The crystals were rinsed with cold propyl acetate/hexanes and then dried under high vacuum at 70° C. to provide 464 mg of N-[2-(4-amino-2-ethoxymethyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)-1,1-dimethylethyl]-2-methylpropionamide as an off white crystalline solid, mp 154.5-155.5° C. Anal. calcd for C20H28N6O2: % C, 62.48; % H, 7.34; % N, 21.86. Found: % C, 62.14; % H, 7.62; % N, 21.71.

1. customThe reaction mixture was quenched with aqueous saturated sodium bicarbonate
2. additiondiluted with dichloromethane (50 mL)
3. customThe organic layer was separated
4. washwashed sequentially with water and brine
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure to an amber foam
8. dissolutionThis material was dissolved in hot propyl acetate (10 mL)
9. temperatureto cool overnight
10. additionHexanes were added
11. temperaturethe now cloudy solution was heated until clear and
12. customformed
13. customThe solvent was removed by pipette
14. washThe crystals were rinsed with cold propyl acetate/hexanes
15. customdried under high vacuum at 70° C.