反应详情

温度

45 °C

A solution of 2-{3-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-azetidin-1-yl}-2-methyl-propionitrile (0.26 g, 0.6 mmol) in DMSO (5 mL) was treated with potassium carbonate (16 mg, 0.12 mmol) followed by hydrogen peroxide (30% aq., 0.33 mL) and the mixture was heated at 45° C. for 18 hours then at 50° C. for a few more hours. Further hydrogen peroxide (33 mL, 30% aq.) was added and the mixture heated at 50° C. for 18 hours. After cooling, water was added and the mixture was extracted with EtOAc (×5). The combined organic extracts were dried (Na2SO4), and concentrated in vacuo and the residue purified by flash chromatography (SiO2, first time with 0-10% MeOH in EtOAc then second time with 0-5% MeOH in DCM). Further purification was by reverse-phase preparative HPLC (Gemini C18 column, gradient 30-40% MeOH in H2O+0.1% HCO2H). A solution of the product in a mixture of chloroform and DCM was treated with 0.2M HCl in ether (0.32 mL) and then concentrated in vacuo to give 446 (27 mg, 9%). LCMS: RT=7.41 min, [M+H]+=453. 1H NMR δ (ppm) (DMSO-d6): 10.79 (1 H, s), 8.34-8.28 (1 H, m), 8.06 (1 H, s), 7.82 (1 H, d, J=17.45 Hz), 7.65 (1 H, d, J=4.94 Hz), 7.27-7.16 (1 H, m), 7.07 (1 H, d, J=1.80 Hz), 5.80-5.72 (1 H, m), 4.47 (1 H, td, J=10.76, 4.67 Hz), 4.37-4.26 (3 H, m), 4.20-3.94 (3 H, m), 3.41 (2 H, q, J=4.96 Hz), 1.55-1.45 (12 H, m)

1. waitat 50° C. for a few more hours
2. temperaturethe mixture heated at 50° C. for 18 hours
3. temperatureAfter cooling
4. extractionthe mixture was extracted with EtOAc (×5)
5. dry with materialThe combined organic extracts were dried (Na2SO4)
6. concentrationconcentrated in vacuo
7. customthe residue purified by flash chromatography (SiO2, first time with 0-10% MeOH in EtOAc
8. customFurther purification
9. additionA solution of the product in a mixture of chloroform and DCM
10. additionwas treated with 0.2M HCl in ether (0.32 mL)
11. concentrationconcentrated in vacuo