反应详情

2-{4-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-piperidin-1-yl}-2-methyl-propionitrile (346 mg, −50% pure, −0.40 mmol) was treated with concentrated sulphuric acid (5 mL) and the mixture was stirred for 5.5 hours then diluted with ice chips (˜50 mL) and made basic with solid sodium carbonate. The mixture was extracted with 10% MeOH in DCM (×4) and the combined organic extracts were dried (Na2SO4) and concentrated in vacuo. The resultant residue was purified by flash chromatography (SiO2, 0-5% MeOH in DCM first time then 0-100% EtOAc in DCM) to give 483 as a white solid (36 mg, 19%). LCMS: RT=3.28 min, [M+H]+=481. 1H NMR δ (ppm) (DMSO-d6): 9.54 (1 H, s), 8.27 (1 H, d, J=8.13 Hz), 8.05 (1 H, s), 7.98 (1 H, s), 7.86 (1 H, s), 7.05 (1 H, d, J=8.29 Hz), 6.90 (1 H, s), 5.81-5.73 (1 H, m), 4.32 (2 H, s), 3.41-3.30 (4 H, m), 3.12 (1 H, m), 2.83 (1 H, m), 2.13 (2 H, d, J=13.80 Hz), 1.99 (1 H, d, J=13.56 Hz), 1.72 (1 H, s), 1.50 (12 H, d, J=6.50 Hz). 1 Proton obscured by water peak

1. additionthen diluted with ice chips (˜50 mL)
2. extractionThe mixture was extracted with 10% MeOH in DCM (×4)
3. dry with materialthe combined organic extracts were dried (Na2SO4)
4. concentrationconcentrated in vacuo
5. customThe resultant residue was purified by flash chromatography (SiO2, 0-5% MeOH in DCM first time