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

Participants

Reaction Steps

HOBT (149 mg) and EDCI (187 mg) were added to a solution of 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (100 mg) in THF (4 mL). The resulting solution was stirred for 2 h. Ethyl 3-{4-fluoro-7-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D45) (186 mg) in THF (4 mL) was added. The reaction mixture was stirred at RT overnight. TBAF (612 mg) was then added. The reaction vessel was sealed and heated in Biotage Initiator using initial normal to 120° C. for 2.5 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 (25% EtOAc in hexane) to afford ethyl 3-[7-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-4-fluoro-1H-indol-3-yl]propanoate (D47) (203 mg) as a pale yellow solid. MS (ES): C25H23FN4O4 requires 462; found 463.2 (M+H+).

Provenance & Evidence