1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → ethyl 3-(4-fluoro-7-{5-[6-[(1-methylethyl)oxy]-5-(methyloxy)-3-pyridinyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoate

Participants

Reaction Steps

HOBT (161 mg) and EDCI (203 mg) were added to a solution of 6-[(1-methylethyl)oxy]-5-(methyloxy)-3-pyridinecarboxylic acid (110 mg) in THF (4 mL). The resulting solution was stirred for 2 hours. Ethyl 3-{4-fluoro-7-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D45) (199 mg) in THF (4 mL) was added, and the reaction mixture was stirred at RT overnight. TBAF (780 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 (10% EtOAc in hexane) to afford ethyl 3-(4-fluoro-7-{5-[6-[(1-methylethyl)oxy]-5-(methyloxy)-3-pyridinyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoate (D50) (158 mg) as a white solid. δH (CDCl3, 400 MHz): 1.25 (3H, t), 1.47 (6H, d), 2.76 (2H, t), 3.24 (2H, t), 4.01 (3H, s), 4.15 (2H, q), 5.55 (1H, m), 6.91 (1H, dd), 7.14 (1H, d), 7.76 (1H, d), 8.06 (1H, dd), 8.64 (1H, d), 9.69 (1H, br s). MS (ES): C24H25FN4O5 requires 468; found 469.2 (M+H+).

Provenance & Evidence