反应详情

2-Chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (PREPARATION x1, 17.3 g, 71.9 mmol) was dissolved in THF (250 mL). To the resulting suspension was added lithium aluminum hydride in THF (2.0 M, 46.7 mL, 93 mmol) dropwise through an addition funnel at 0° C. to give a clear light-brown solution. The reaction mixture was allowed to warm to room temperature and was stirred for 3 hours. Ethyl acetate (˜25 mL) was added at 0° C. in portions; a saturated aqueous solution of NH4Cl (125 mL) was then added dropwise until bubbling ceased. The upper organic layer was decanted, concentrated in vacuo and then partitioned between brine and ethyl acetate. The murky bottom layer was then extracted with ethyl acetate (3×) and the combined organic layers were dried over MgSO4, filtered, and concentrated. The product was triturated with ether/ethyl acetate and collected by filtration under nitrogen to give the title compound (9.6 g, 59%). 1H NMR (DMSO-d6) δ 2.88-2.94 (m, 2H), 3.12 (t, 1H), 3.26-3.28 (m, 1H), 3.42-3.51 (m, 2H), 3.86-3.92 (m, 2H), 4.19-4.21 (d, J=8.0 Hz, 1H), 5.96 (br s, 1H), 7.36 (s, 1H). ESI-MS m/z [M+H]+ calc'd for C9H9ClN4O2, 241.04. found 241.1.

1. customto give a clear light-brown solution
2. customuntil bubbling
3. customThe upper organic layer was decanted
4. concentrationconcentrated in vacuo
5. custompartitioned between brine and ethyl acetate
6. extractionThe murky bottom layer was then extracted with ethyl acetate (3×)
7. dry with materialthe combined organic layers were dried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customThe product was triturated with ether/ethyl acetate
11. filtrationcollected by filtration under nitrogen