1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 6-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indole

Participants

Reaction Steps

EDCI (1.17 g) and HOBT (1.01 g) were added to a solution of 5-chloro-6-[(1-methylethyl)oxy]-3-pyridinecarboxylic acid (657 mg) in THF (5 mL) at RT. The resulting solution was stirred for 30 min. N-hydroxy-1H-indole-6-carboximidamide (D100) (1.00 g) in THF (5 mL) was added and the reaction mixture was stirred at RT for 2 hours. TBAF (3.2 g) was then added. The reaction vessel was sealed and heated in Biotage Initiator using initial normal to 120° C. for 90 min. After cooling, the reaction was quenched with water, and extracted with EtOAc for 3 times. The combined organic solution was washed with brine, and dried over anhydrous sodium sulfate. The dried solution was concentrated. The residue was purified by column chromatography to afford 6-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indole (D101) (1.13 g) as a pale yellow solid. δH (CDCl3, 400 MHz): 1.47 (6H, d), 5.51 (1H, m), 6.65 (1H, s), 7.37 (1H, t), 7.76 (1H, d), 7.93 (1H, d), 8.26 (1H, s), 8.42 (2H, d), 8.90 (1H, d). MS (ES): C18H15ClN4O2 requires 354. found 355.1 (M+H+).

Provenance & Evidence