反应详情

温度

60 °C

In a 250 mL round bottomed flask, 6-fluoro-3-iodo-1-tosyl-1H-indole-5-carbohydrazide (880 mg, 1.86 mmol) was treated with THF (10 mL) and 2-isothiocyanatopropane (0.56 mL, 5.58 mmol) and heated to 60° C. for 1 h. The THF was removed under reduced pressure (rotary evaporator) and replaced with DMF (5.0 mL) and the solution was treated with EDC HCl (Aldrich, St. Louis, Mo., 535 mg, 2.79 mmol) and heated at 90° C. for 30 min. The reaction mixture was cooled to RT and treated with water and extracted with EtOAc (2×50 mL), washed with brine (2×50 mL) and dried over MgSO4, filtered and concentrated. Purification of the crude residue on the ISCO Combiflash Rf (40 g Redisep column, using a gradient of 0-100% EtOAc in hexanes) afforded 5-(6-fluoro-3-iodo-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine (407 mg, 0.75 mmol, 40.5% yield) as an off-white amorphous solid. MS (ESI, pos. ion) m/z: 540.8 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.20 (1H, s), 8.03 (2H, m, J=8.4 Hz), 7.95 (1H, d, J=11.2 Hz), 7.81 (1H, d, J=7.4 Hz), 7.71 (1H, d, J=6.7 Hz), 7.44 (2H, m, J=8.2 Hz), 3.74 (1H, dq, J=13.4, 6.6 Hz), 2.35 (3H, s), 1.21 (6H, d, J=6.5 Hz).

1. customThe THF was removed under reduced pressure (rotary evaporator)
2. temperatureheated at 90° C. for 30 min
3. temperatureThe reaction mixture was cooled to RT
4. extractionextracted with EtOAc (2×50 mL)
5. washwashed with brine (2×50 mL)
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customPurification of the crude residue on the ISCO Combiflash Rf (40 g Redisep column