反应详情

A solution of 1-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol (500 mg, 1.59 mmol) dissolved in 15 mL of anhydrous CH2Cl2 was treated with thionyl chloride (232 mL, 3.18 mmol). After 30 minutes, the reaction mixture was concentrated under reduced pressure. The resulting material was concentrated from ethanol and then dissolved in 15 mL of TFA. The mixture was placed in pressure flask and treated with 250 mg of PtO2. The mixture was then shaken under H2 at 50 PSI (3.4×105 Pa) for 3 hours. The reaction mixture was filtered through a pad of CELITE filter agent. The pad was rinsed with CH2Cl2 and 2-propanol and the combined filtrates were concentrated under reduced pressure to give a syrup. The syrup was dissolved in 50 mL of hot ethanol and crystals formed upon cooling. The crystals were isolated by filtration and were then partitioned between dilute NH4OH solution (25 mL) and CH2Cl2 (25 mL). The organic portion was washed with additional dilute NH4OH solution (2×), H2O and brine. The organic portion was concentrated to give a syrup. Crystallization from HCl in ethanol gave the title compound as a yellow powder, m.p. 222-227° C. 1H NMR (300 MHz, DMSO-d6) δ 7.87 (s, 2H), 4.74 (s, 2H), 4.18 (s, 2H), 3.50 (q, J=7.0 Hz, 2H), 3.06 (t, J=5.1 Hz, 2H), 2.71 (t, J=6.2 Hz, 2H), 2.08 (m, 2H), 1.17 (s, 6H), 1.14 (t, J=7.0 Hz, 3H); 13C NMR (125 MHz, DMSO-d6) δ 150.5, 143.9, 132.8, 121.3, 119.5, 119.3, 65.4, 63.7, 54.5, 54.4, 22.1, 20.9, 20.7, 14.8; MS (ESI) m/z 302 (M+H)30; Anal. calcd for C16H23N5O.HCl: C, 56.88; H, 7.16; N, 20.73; Cl, 10.51. Found: C, 56.61; H, 8.09; N, 20.51; Cl, 10.88.

1. concentrationthe reaction mixture was concentrated under reduced pressure
2. concentrationThe resulting material was concentrated from ethanol
3. dissolutiondissolved in 15 mL of TFA
4. customThe mixture was placed in pressure flask
5. additiontreated with 250 mg of PtO2
6. filtrationThe reaction mixture was filtered through a pad of CELITE
7. filtrationfilter agent
8. washThe pad was rinsed with CH2Cl2 and 2-propanol
9. concentrationthe combined filtrates were concentrated under reduced pressure
10. customto give a syrup
11. customcrystals formed
12. temperatureupon cooling
13. customThe crystals were isolated by filtration
14. customwere then partitioned between dilute NH4OH solution (25 mL) and CH2Cl2 (25 mL)
15. washThe organic portion was washed with additional dilute NH4OH solution (2×), H2O and brine
16. concentrationThe organic portion was concentrated
17. customto give a syrup
18. customCrystallization from HCl in ethanol