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

Participants

Reaction Steps

To the solution of 5-chloro-6-[(1-methylethyl)oxy]-3-pyridinecarboxylic acid (1.39 g) in tetrahydrofuran (50 mL) were added EDCI (1.69 g) and HOBT (1.35 g). The resulting solution was stirred at room temperature for 1 hour. Then ethyl 3-{6-fluoro-7-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D145) (1.72 g) was added and the solution was stirred at room temperature for another 2 hours. THF was removed in vacuo and the residue was dissolved in ethyl acetate (50 mL), washed with water (2×10 mL), dried over sodium sulphate and concentrated. The residue was dissolved in THF (3 mL), TBAF (6.13 g) was added and the reaction solution was stirred in the microwave (120° C., 2.5 hours). The reaction solution was poured into ethyl acetate (100 mL), washed with water (3×20 mL) and dried over sodium sulphate. The organic solution was concentrate and the residue was purified by column chromatography to afford ethyl 3-[7-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-6-fluoro-1H-indol-3-yl]propanoate (D149) (520 mg) as a white solid. MS (ES): C23H22ClFN4O4 requires 472; found 473.2 (M+H+)

Provenance & Evidence