反应详情

To 1-[(cyclopropylmethyl)amino]-4-hydroxy-3-{7-[(methoxymethoxy)methyl]-1,1-dioxido-4H -thieno[2,3-e][1,2,4]thiadiazin-3-yl}quinolin-2(1H)-one (384.7 mg, 0.78 mmol) was added a solution of hydrogen chloride in dioxane (4N, 7.8 mL) at 0° C. The solution warmed to room temperature and stirred for 5.5 hours and concentrated under reduced pressure. This solid was suspended in dichloromethane (7.8 mL) and to the suspension was added 1,8-diazabicyclo[5.4.0] undec-7-ene (0.6 mL, 4.01 mmol) and diphenylphosphoryl azide (0.85 mL, 3.94 mmol) at room temperature and stirred overnight. The solution was concentrated in vacuo. The residue was purified by chromatography, eluting with 1% triethylamine/dichloromethane to give a triethylamine salt of 3-[7-(azidomethyl)-1,1-dioxido -4H-thieno[2,3-e][1,2,4]thiadiazin-3-yl]-1-[(cyclopropylmethyl)amino]-4-hydroxyquinolin-2(1H)-one (357 mg, 79%). MS (ESI−) m/z 470 (M−H)−. 1H NMR (300 MHz, DMSO-d6) δ 0.22 (m, 2H) 0.46 (br d, J=7.35 Hz, 2H) 1.01 (m, 1H) 4.52 (s, 2H) 5.98 (t, J=6.62 Hz, 1H) 7.24 (s, 1H) 7.40 (m, 1H) 7.56 (m, 1H) 8.05 (m, 1H).

1. concentrationconcentrated under reduced pressure
2. stirringstirred overnight
3. concentrationThe solution was concentrated in vacuo
4. customThe residue was purified by chromatography
5. washeluting with 1% triethylamine/dichloromethane