反应详情

温度

100 °C

130 mg of 6-chloro-2-[2-(4-fluoro-2,3-dihydroindol-1-yl)-2-oxoethyl]-3H-pyrimidin-4-one, 3 ml of 1,4-dioxane, 104 mg of 2-fluoropyridine-4-boronic acid pinacol ester, 50 mg of tetrakis(triphenylphosphine)palladium(0), and 0.58 ml of an aqueous 1.5 M cesium carbonate solution are successively placed in a three-necked round-bottomed flask under argon and with stirring. The mixture is heated at a temperature of 100° C. for 20 hours, and then filtered while hot. After cooling to ambient temperature, the filtrate is concentrated to dryness under reduced pressure. The residue is taken up in a mixture of 20 ml of dichloromethane and 30 ml of water. After settling out, the organic phase is separated and the aqueous phase is extracted with dichloromethane. The aqueous phase is concentrated to dryness under reduced pressure. The residue is taken up in a mixture of 30 ml of ethyl acetate and a few drops of ethanol, and then washed with 5 ml of water. After settling out, the organic phase is separated and the aqueous phase is extracted with 2×20 ml of ethyl acetate. The organic extracts are combined, dried over magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. The residue is taken up in 1 ml of dioxane and the mixture is refluxed, and then filtered through sintered glass. After drying of the isolated solid, 44 mg of 2-[2-(4-fluoro-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-(2-fluoropyridin-4-yl)-3H-pyrimidin-4-one are obtained in the form of a beige solid, the characteristics of which are the following:

1. filtrationfiltered while hot
2. temperatureAfter cooling to ambient temperature
3. concentrationthe filtrate is concentrated to dryness under reduced pressure
4. additionThe residue is taken up in a mixture of 20 ml of dichloromethane and 30 ml of water
5. customthe organic phase is separated
6. extractionthe aqueous phase is extracted with dichloromethane
7. concentrationThe aqueous phase is concentrated to dryness under reduced pressure
8. additionThe residue is taken up in a mixture of 30 ml of ethyl acetate and a few drops of ethanol
9. washwashed with 5 ml of water
10. customthe organic phase is separated
11. extractionthe aqueous phase is extracted with 2×20 ml of ethyl acetate
12. dry with materialdried over magnesium sulfate
13. filtrationfiltered
14. concentrationconcentrated to dryness under reduced pressure
15. temperaturethe mixture is refluxed
16. filtrationfiltered through sintered glass
17. dry with materialAfter drying of the isolated solid, 44 mg of 2-[2-(4-fluoro-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-(2-fluoropyridin-4-yl)-3H-pyrimidin-4-one
18. customare obtained in the form of a beige solid