1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 5-{3-[2-(Hydroxymethyl)-1H-indol-5-yl]-1,2,4-oxadiazol-5-yl}-2-[(1-methylethyl)oxy]benzonitrile

Participants

Reaction Conditions

Reaction Steps

EDCI (144 mg) and HOBT (104 mg) were added to a solution of 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (can be prepared as described on WO2005/58848, 144 mg) in DMF (5 mL) at RT. The resulting solution was stirred for 15 min. N-Hydroxy-2-(hydroxymethyl)-1H-indole-5-carboximidamide (D25) (144 mg) was added and the reaction mixture was stirred at RT for 1 hour. The reaction mixture was heated to 80° C. and stirred at that temperature for 4 hours. EtOAc (50 mL) was added and the organic solution was washed with water (50 mL), saturated aqueous sodium bicarbonate solution (50 mL) and water (50 mL). The organic fraction was dried over anhydrous magnesium sulfate. The dried solution was concentrated. The residue was recrystallized from EtOAc/ether to afford 5-{3-[2-(hydroxymethyl)-1H-indol-5-yl]-1,2,4-oxadiazol-5-yl}-2-[(1-methylethyl)oxy]benzonitrile (E12) (70 mg) as a light brown solid. δH (DMSO-d6, 400 MHz): 1.39 (6H, d), 4.65 (2H, d), 4.99 (1H, m), 5.36 (1H, t), 6.46 (1H, s), 7.49 (1H, d), 7.56 (1H, d), 7.79 (1H, dd), 8.28 (1H, dd), 8.42 (1H, d), 8.52 (1H, d), 11.43 (1H, s). MS (ES): C21H18N4O3 requires 374; found 375.0 (M+H+).

Provenance & Evidence