1,2-Dichloroethane → Ethyl 4-[4-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-1-yl]butanoate

Participants

Reaction Steps

A mixture of 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (can be prepared as described in WO2005/58848) (1.21 g, 5.88 mmol), EDC (1.35 g, 7.05 mmol) and HOBt (1.08 g, 7.05 mmol) in dry DMF (85 ml) was stirred for 20 minutes at RT. Added ethyl 4-{4-[(hydroxyamino)(imino)methyl]-1H-indol-1-yl}butanoate (D59) (1.70 g, 5.88 mmol) and stirred at RT for 1 hour. Heated mixture at 80° C. for 5 hours and left overnight at RT. Heated at 80° C. for 6 hours then evaporated off the DMF. Added EtOAc (200 ml) and washed with sat. NaHCO3 (200 ml) and water (200 ml). Dried over MgSO4 and evaporated off the solvent. Subjected the residue to chromatography using the biotage (EtOAc/hexane 1:2) and evaporated the cleanest fractions to yield 1.42 g the title compound as a white solid. δH (400 MHz, d6-DMSO) 1.15 (3H, t), 1.39 (6H, d), 2.04 (2H, apparent quintet), 2.24 (2H, t), 4.00 (2H, q), 4.31 (2H, t), 4.94-5.04 (1H, m), 7.10 (1H, dd), 7.31 (1H, t), 7.56-7.60 (2H, m), 7.77 (1H, d), 7.95 (1H, d), 8.45 (1H, dd), 8.56 (1H, d). MS (ES) C26H26N4O4 requires 458; found 459 (MH+).

Provenance & Evidence