反应详情

HOBT (672 mg) and EDCI (841 mg) were added to a solution of 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (450 mg) in THF (10 mL). The resulting solution was stirred for 1 hour. Ethyl 3-{6-fluoro-7-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D145) (836 mg) in THF (5 mL) was added, and the reaction mixture was stirred at RT for 2 hours. TBAF (2.02 g) was then added. The reaction vessel was sealed and heated in Biotage Initiator using initial normal to 120° C. for 2 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 to afford ethyl 3-[7-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-6-fluoro-1H-indol-3-yl]propanoate (D148) (875 mg) as a yellow solid. MS (ES): C25H23FN4O4 requires 462; found 463.2 (M+H+).

1. stirringthe reaction mixture was stirred at RT for 2 hours
2. customThe reaction vessel was sealed
3. temperatureheated in Biotage Initiator
4. customnormal to 120° C.
5. customfor 2 hours
6. temperatureAfter cooling
7. customthe reaction was quenched with water
8. extractionextracted with EtOAc for 3 times
9. washThe combined organic solution was washed with brine
10. dry with materialdried over anhydrous sodium sulfate
11. concentrationThe dried solution was concentrated
12. customThe residue was purified by column chromatography