反应详情

EDCI (385 mg) and HOBT (332 mg) were added to a solution of 6-[(1-methylethyl)oxy]-5-(trifluoromethyl)-3-pyridinecarboxylic acid (250 mg) in THF (5 mL) at RT. The resulting solution was stirred for 30 mins. Ethyl 3-{6-[(Z)-(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D107) (413 mg) in THF (5 mL) was added and the reaction mixture was stirred at RT for 2 hours. TBAF (1.1 g) was then added. The reaction vessel was sealed and heated in Biotage Initiator using initial normal to 120° C. for 90 mins. After cooling, the reaction was quenched with water, and extracted with EA for 3 times. The combined organic solution was washed with brine, dried over anhydrous sodium sulfate. The dried solution was concentrated. The residue was purified by column chromatography (20% EtOAc in hexane) to afford ethyl 3-(6-{5-[6-[(1-methylethyl)oxy]-5-(trifluoromethyl)-3-pyridinyl]-1,2,4-oxadiazol-3-yl}-1H-indol-3-yl)propanoate (D109) (310 mg) as a pale yellow solid. δH (CDCl3, 400 MHz): 1.25 (3H, t), 1.45 (6H, d), 2.74 (2H, t), 3.15 (2H, t), 4.16 (2H, q), 5.60 (1H, m), 7.17 (1H, t), 7.73 (1H, d), 7.94 (1H, dd), 8.21 (2H, dd), 8.64 (1H, t), 9.14 (1H, d). δF (CDCl3, 376 MHz): −64.3. MS (ES): C24H23F3N4O4 requires 488; found 489.2 (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 90 mins
6. temperatureAfter cooling
7. customthe reaction was quenched with water
8. extractionextracted with EA 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 (20% EtOAc in hexane)