1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indole

Participants

Reaction Steps

To a solution of 3-chloro-4-[(1-methylethyl)oxy]benzoic acid (D32) (5.2 g) in tetrahydrofuran (15 mL) stirred at room temp was added EDCI (5.8 g) and HOBT (4.6 g). The reaction mixture was stirred at room temperature for 2 h. Then N-hydroxy-1H-indole-7-carboximidamide (3.5 g) was added. The reaction mixture was stirred at 60° C. for 2 h, and then TBAF (15.7 g) was added. The reaction vessel was sealed and heated in Biotage Initiator using initial normal to 130° C. for 3 h. After cooling the reaction, solvent was removed. Water (200 mL) and ethanol (50 mL) was added. The precipitate was collected, washed with acetonitrile and dried in vacuo to afford 7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indole (D51) (5.1 g) as a yellow solid. δH (CDCl3, 400 MHz): 1.47 (6H, d), 4.70-4.76 (1H, m), 6.68 (1H, dd), 7.08 (1H, d), 7.29 (1H, t), 7.40 (1H, t), 7.85 (1H, d), 8.11 (1H, dd), 8.13 (1H, dd), 8.30 (1H, d), 9.86 (1H, s). MS (ES): C19H16ClN3O2 requires 353; found 354.1 (M+H+)

Provenance & Evidence