反应详情

温度

0 °C

To a 10 mL round bottomed flask was added 2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenylamino)-9-(4-fluorophenyl)-8,9-dihydro-5H-[1,2,4]triazolo[1,5-a]azepin-7(6H)-one (100 mg, 0.214 mmol, from Example 137). The vessel was purged with nitrogen. DCM (1 mL) was added and the solution was cooled to 0° C. DAST (0.071 mL, 0.535 mmol) was added and the stirred reaction mixture was allowed to slowly warm to ambient temperature. After 18 h, saturated aqueous NaHCO3 (200 mL) was carefully added, and the mixture was extracted with EtOAc (300 mL). The organics were washed with brine (100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified using reverse phase preparatory HPLC (MeOH/water/trifluoroacetic acid) to afford the titled compound (8.2 mg, 6% yield) as a TFA salt. LC-MS (M+H)+ 489.2. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 9.14 (1 H, br. s.), 8.11 (1 H, s), 7.03-7.45 (7 H, m), 4.59 (1 H, br. s.), 4.26-4.46 (2 H, m), 3.87 (3 H, s), 2.29-2.84 (4 H, m).

1. customThe vessel was purged with nitrogen
2. additionDCM (1 mL) was added
3. customthe stirred reaction mixture
4. temperatureto slowly warm to ambient temperature
5. extractionthe mixture was extracted with EtOAc (300 mL)
6. washThe organics were washed with brine (100 mL)
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe crude product was purified