反应详情

To a solution of 8-azetidin-3-yl-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene TFA salt 235 (200 mg, 0.42 mmol) in IMS (industrial methylated spirits, 3 mL) was added triethylamine (0.20 mL, 1.47 mmol) and methyl vinyl sulfone (0.09 mL, 1.05 mmol) and the reaction mixture was stirred at RT (room temperature) for 18 hours. The reaction mixture was concentrated in vacuo and the residue purified by flash chromatography (SiO2, 0-5% MeOH in DCM). Freeze-drying from methanol and water gave 320 as a pale yellow solid (135 mg, 68%). LCMS: RT=3.10 min, [M+H]+=474. 1H NMR δ (ppm) (DMSO-d6): 8.35 (1 H, d, J=8.19 Hz), 8.11 (1 H, s), 7.29 (1 H, d, J=8.27 Hz), 7.20 (1 H, s), 5.85-5.76 (1 H, m), 4.41-4.35 (3 H, m), 4.14 (3 H, d, J=59.98 Hz), 3.68 (2 H, s), 3.53-3.41 (3 H, m), 3.13 (3 H, s), 1.55 (6 H, d, J=6.60 Hz). 2 Protons obscured by water peak

1. concentrationThe reaction mixture was concentrated in vacuo
2. customthe residue purified by flash chromatography (SiO2, 0-5% MeOH in DCM)
3. dry with materialFreeze-drying from methanol and water