反应详情

HOBT (163 mg) and EDCI (204 mg) were added to a solution of 5-chloro-6-[(1-methylethyl)oxy]-3-pyridinecarboxylic acid (118 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) (208 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-[7-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-4-fluoro-1H-indol-3-yl]propanoate (D48) (224 mg) as a pale yellow solid. δH (CDCl3, 400 MHz): 1.25 (3H, t), 1.46 (6H, d), 2.76 (2H, t), 3.24 (2H, t), 4.14 (2H, q), 5.51 (1H, m), 6.91 (1H, dd), 7.15 (1H, d), 8.04 (1H, dd), 8.43 (1H, d), 8.91 (1H, d), 9.67 (1H, br s). MS (ES): C23H22ClFN4O4 requires 472; found 473.2 (M+H+).

1. stirringthe reaction mixture was stirred at RT overnight
2. customThe reaction vessel was sealed
3. temperatureheated in Biotage Initiator
4. customnormal to 120° C.
5. customfor 2.5 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 (10% EtOAc in hexane)