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

Participants

Reaction Steps

HOBT (166 mg) and EDCI (199 mg) were added to a solution of 3-chloro-4-[(1-methylethyl)oxy]benzoic acid (115 mg) in THF (4 mL). The reaction mixture was stirred at RT for 2 hours. Ethyl 3-{4-fluoro-7-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D45) (205 mg) in THF (4 mL) was added. Then stirring continued overnight. TBAF (760 mg) was then added. The reaction vessel was sealed and heated in Biotage Initiator using initial normal to 120° C. for 3 hours. 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 (15% EtOAc in hexane) to afford ethyl 3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-4-fluoro-1H-indol-3-yl]propanoate (D46) (216 mg) as a pale yellow solid. δH (CDCl3, 400 MHz): 1.25 (3H, t), 1.47 (6H, d), 2.76 (2H, t), 3.24 (2H, t), 4.14 (2H, q), 4.74 (1H, m), 6.91 (1H, dd), 7.09 (1H, d), 7.14 (1H, d), 8.04 (1H, dd), 8.10 (1H, dd), 8.28 (1H, d), 9.71 (1H, br s). MS (ES): C24H23ClFN3O4 requires 471; found 472.2 (M+H+).

Provenance & Evidence