反应详情

To a mixture of 2-chloro-5-(2,2,2-trifluoroethyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (768 mg, 2.38 mmol) and iodomethane (0.595 ml, 9.52 mmol) in DMSO (15 ml) at 0° C. was added sodium 2-methylpropan-2-olate (343 mg, 3.57 mmol). The ice-bath was removed and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was poured into water and extracted with EtOAc. The organic layers were washed with water (containing Na2S2O3), dried and concentrated in vacuo to give a crude oil. The crude residue was purified by silica gel chromatography (hexane/ethyl acetate, 19:1 to 11:9) to afford 2-chloro-6a-methyl-5-(2,2,2-trifluoroethyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (191 mg, 0.566 mmol, 24% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.41 (s, 3H) 3.17-3.28 (m, 1H) 3.55 (td, J=12.13, 3.03 Hz, 1H) 3.68 (d, J=11.62 Hz, 1H) 3.89-4.07 (m, 3H) 4.75-5.04 (m, 2H) 8.31 (s, 1H). MS [M+H] found 337.

1. customThe ice-bath was removed
2. additionThe reaction mixture was poured into water
3. extractionextracted with EtOAc
4. washThe organic layers were washed with water (containing Na2S2O3)
5. customdried
6. concentrationconcentrated in vacuo
7. customto give a crude oil
8. customThe crude residue was purified by silica gel chromatography (hexane/ethyl acetate, 19:1 to 11:9)