Tetrahydrofuran → 5-(6-fluoro-3-iodo-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence