反应详情

温度

100 °C

120 mg of 6-chloro-2-[2-(4-fluoro-2,3-dihydroindol-1-yl)-2-oxoethyl]-3H-pyrimidin-4-one, 96 mg of 2-methylpyridine-4-boronic acid pinacol ester, 45 mg of tetrakis(triphenylphosphine)palladium(0), 2.5 ml of 1,4-dioxane and 0.52 ml of an aqueous 1.5 M cesium carbonate solution are successively placed in a 5 ml microwave tube. The resulting suspension is stirred under microwave irradiation at a temperature of 100° C. for 2×1 hour. After cooling to ambient temperature, the reaction mixture is diluted with 6 ml of ethyl acetate and then filtered through Clarcel®. The solid is washed with 3 ml of ethyl acetate, and then the filtrate is treated with 12 ml of water and stirred at ambient temperature for 1.5 hours. After settling out, the organic phase is separated and the aqueous phase is extracted with 3×10 ml of ethyl acetate. The organic extracts are combined, washed with 10 ml of saturated brine, dried over magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. The residue is purified by chromatography on a 25 g cartridge of 15-40 μm silica, by making a solid deposit and eluting with a 95/5 v/v dichloromethane/methanol mixture at a flow rate of 25 ml/min. The fractions containing the desired product are combined and concentrated to dryness under reduced pressure. The residue is taken up twice in diethyl ether, triturated, and then concentrated to dryness under reduced pressure. 46 mg of 2-[2-(4-fluoro-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-(2-methylpyridin-4-yl)-3H-pyrimidin-4-one are thus obtained in the form of a white crystalline powder, the characteristics of which are the following:

1. temperatureAfter cooling to ambient temperature
2. filtrationfiltered through Clarcel®
3. washThe solid is washed with 3 ml of ethyl acetate
4. additionthe filtrate is treated with 12 ml of water
5. stirringstirred at ambient temperature for 1.5 hours
6. customthe organic phase is separated
7. extractionthe aqueous phase is extracted with 3×10 ml of ethyl acetate
8. washwashed with 10 ml of saturated brine
9. dry with materialdried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated to dryness under reduced pressure
12. customThe residue is purified by chromatography on a 25 g cartridge of 15-40 μm silica
13. washeluting with a 95/5 v/v dichloromethane/methanol mixture at a flow rate of 25 ml/min
14. additionThe fractions containing the desired product
15. concentrationconcentrated to dryness under reduced pressure
16. customtriturated
17. concentrationconcentrated to dryness under reduced pressure