反应详情

To a stirred ethanolic solution of 4-(2-(dimethylamino)ethyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-amine (0.088 g, 0.398 mmol) under an argon atmosphere was added methyl thiophene-2-carbimidothioate hydroiodide (0.227 g, 0.795 mmol). The resulting faintly cloudy yellow mixture stirred overnight at room temperature. After 20 hours, argon was bubbled through the mixture, which was then concentrated to afford a residue. The residue was then partitioned between EtOAc (100 mL) and saturated NaHCO3 (˜10 mL) solution. The aqueous layer (pH ˜9) was further extracted with EtOAc, and the combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated to yield a yellow residue. Purification on silica gel (dry chromatography, eluting with 5-7.5% (2M NH3 MeOH)/CH2Cl2) yielded the title compound 9 as a yellow residue (70 mg, 53.3%). 1H NMR (DMSO-d6) δ 7.70 (d, 1H, J=2.7 Hz), 7.57 (d, 1H, J=5.0 Hz), 7.07 (dd, 1H, J=5.0, 3.7 Hz), 6.59 (d, 1H, J=8.2 Hz), 6.30 (brs, 2H), 6.14 (s, 1H), 6.00 (d, 1H, J=8.1 Hz), 4.18-4.02 (m, 2H), 3.41-3.25 (m, 4H+H2O), 2.41 (t, 2H, J=6.7 Hz), 2.17 (s, 6H); ESI-MS (m/z, %): 331 (MH+, 100).

1. waitAfter 20 hours
2. customargon was bubbled through the mixture, which
3. concentrationwas then concentrated
4. customto afford a residue
5. customThe residue was then partitioned between EtOAc (100 mL) and saturated NaHCO3 (˜10 mL) solution
6. extractionThe aqueous layer (pH ˜9) was further extracted with EtOAc
7. washthe combined organic layers were washed with brine
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated
11. customto yield a yellow residue
12. customPurification on silica gel (dry chromatography, eluting with 5-7.5% (2M NH3 MeOH)/CH2Cl2)