Cesium carbonate → 4-cyclopropyl-5-fluoro-N-[3-fluoro-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amine

温度

90 °C

3-Fluoro-5-(1,3-thiazol-5-yl)aniline (0.91 g, 4.69 mmol), 2-chloro-4-cyclopropyl-5-fluoropyrimidine (0.809 g, 4.69 mmol), palladium(II) acetate (0.105 g, 0.469 mmol), Xantphos (0.407 g, 0.703 mmol), and cesium carbonate (3.05 g, 9.37 mmol) were added to a dry flask. Degassed with argon, and then added dioxane (20 mL). The reaction mixture was degassed with argon for five minutes, and then heated to 90° C. After 2 hours, the reaction mixture was cooled, diluted with ethyl acetate, filtered through celite, and concentrated. The residue was purified by column chromatography on silica gel, eluting with ethyl acetate and hexanes to afford solids. The solids were dissolved in hot ethyl acetate (25 mL) and then triturated with hexanes (50 mL) while cooling. After 2 hours, the mixture was filtered to afford 4-cyclopropyl-5-fluoro-N-[3-fluoro-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amine (1.2 g, 3.6 mmol, 78%). MS ESI: [M+H]+ m/z 331.1.

1. customDegassed with argon
2. customThe reaction mixture was degassed with argon for five minutes
3. temperaturethe reaction mixture was cooled
4. additiondiluted with ethyl acetate
5. filtrationfiltered through celite
6. concentrationconcentrated
7. customThe residue was purified by column chromatography on silica gel
8. washeluting with ethyl acetate and hexanes
9. customto afford solids
10. customtriturated with hexanes (50 mL)
11. temperaturewhile cooling
12. waitAfter 2 hours
13. filtrationthe mixture was filtered

ORDレコード

ord-24a47243042844b1a8b3776398fa1b1a

出典データセット

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08551984B2