反应详情

To a stirred solution of tert-butyl 4-(1-ethyl-6-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-oxopiperazine-1-carboxylate (5.00 g, 13.80 mmol) and 2-pyridine methanol (1.60 mL, 16.56 mmol) in dimethyl sulphoxide (50 mL), under a nitrogen atmosphere, is added 60% sodium hydride (0.662 g, 16.56 mmol) portionwise. The reaction is stirred at room temperature for 1 h and then heated at 135° C. overnight. The reaction is cooled to room temperature and further 60% sodium hydride (0.662 g, 16.56 mmol) added, and the reaction stirred overnight at room temperature. The reaction is poured onto brine (ca. 500 mL) and the product extracted with CHCl3 (ca. 2×300 mL). The combined organic extracts are dried over magnesium sulphate, filtered, and concentrated in vacuo to give a brown oil. This is purified by column chromatography on silica, eluting with 0 to 80% EtOAc in DCM, to give the title compound as an orange foam (4.952 g, 10.97 mmol). MS (m/z): 452 (M+1).

1. temperatureheated at 135° C. overnight
2. temperatureThe reaction is cooled to room temperature
3. stirringthe reaction stirred overnight at room temperature
4. additionThe reaction is poured onto brine (ca. 500 mL)
5. extractionthe product extracted with CHCl3 (ca. 2×300 mL)
6. dry with materialThe combined organic extracts are dried over magnesium sulphate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto give a brown oil
10. customThis is purified by column chromatography on silica
11. washeluting with 0 to 80% EtOAc in DCM