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

温度

90 °C

The product of Step 2 (0.93 g, 4.79 mmol), 2-chloro-4-(trifluoromethyl)pyrimidine (0.874 g, 4.79 mmol), palladium(II) acetate (0.107 g, 0.479 mmol), xantphos (0.416 g, 0.718 mmol), and cesium carbonate (3.12 g, 9.58 mmol) were added to a dry flask. The flask was degassed with argon, and then dioxane (20 ml) was added. 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 (EtOAc/hexane gradient) 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 N-[3-fluoro-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (1.18 g, 3.47 mmol, 72% yield). MS ESI: [M+H]+ m/z 341.1. 1H NMR (500 MHz, DMSO-d6) δ 10.52 (s, 1H); 9.10 (s, 1H); 8.87 (d, J=4.0 Hz, 1H); 8.31 (s, 1H); 7.93 (s, 1H); 7.66-7.62 (m, 1H); 7.35 (d, J=4.5 Hz, 1H); 7.28 (dt, J=8.0 Hz, 1.5 Hz, 1H).

1. customThe flask was degassed with argon
2. additiondioxane (20 ml) was added
3. customThe reaction mixture was degassed with argon for five minutes
4. temperaturethe reaction mixture was cooled
5. additiondiluted with ethyl acetate
6. filtrationfiltered through celite
7. concentrationconcentrated
8. customThe residue was purified by column chromatography on silica gel (EtOAc/hexane gradient)
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-2ee3fd7e975d4cb0aa59e9e3171562d8

出典データセット

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08759366B2