反应详情

A solution of 1H-1,2,4-triazole (0.881 g, 0.0128 mol) in pyridine (3.00 mL) was charged with POCl3 (0.396 mL, 0.00425 mol) and stirred at rt for 15 min. To this mixture was drop wise added methyl trans-4-(5-iodo-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-7-yl)cyclohexanecarboxylate (0.570 g, 0.00142 mol) in pyridine (6.00 mL) and stirred at rt for an additional 2.45 h. The reaction was quenched with excess 2 M of NH3 in i-PrOH (40.00 mL) at 0° C. and allowed to stir at rt for an additional 3 h. The reaction was concentrated in vacuo and partitioned between EtOAc and sat. NaHCO3 and separated. The aqueous was washed with EtOAc (3×) and the combined organic fractions were washed with brine (1×). The aqueous was re-extracted with CHCl3 (3×) and the organic was added to the EtOAc fractions. The combined organic fractions were dried over Na2SO4, filtered and concentrated in vacuo. The crude brown/red solid was purified by chromatography over silica gel [eluting with 5% MeOH in CHCl3] resulting in 438 mg, (76% yield) of the title compound as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.39-1.54 (m, 2H), 1.55-1.71 (m, 2H), 1.92-2.07 (m, 4H), 2.35-2.46 (m, 1H), 3.06-3.19 (m, 1H), 3.61 (s, 3H), 6.77 (br. s., 1H) 7.86 (s, 1H) and 8.44 (br. s., 1H); MS (ES+): m/z 401.85 [MH+].

1. stirringstirred at rt for an additional 2.45 h
2. customThe reaction was quenched with excess 2 M of NH3 in i-PrOH (40.00 mL) at 0° C.
3. stirringto stir at rt for an additional 3 h
4. concentrationThe reaction was concentrated in vacuo
5. custompartitioned between EtOAc and sat. NaHCO3
6. customseparated
7. washThe aqueous was washed with EtOAc (3×)
8. washthe combined organic fractions were washed with brine (1×)
9. extractionThe aqueous was re-extracted with CHCl3 (3×)
10. additionthe organic was added to the EtOAc fractions
11. dry with materialThe combined organic fractions were dried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. customThe crude brown/red solid was purified by chromatography over silica gel [eluting with 5% MeOH in CHCl3]