反应详情

温度

110 °C

Racemic 2-chloro-5-fluoro-4-methylpyrimidine (50.0 mg, 0.341 mmol), methyl-4-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]-4-hydroxy-2,2-dimethylcyclohexanecarboxylate (128 mg, 0.341 mmol), Pd(OAc)2 (15.3 mg, 0.0680 mmol), Xantphos (59.2 mg, 0.102 mmol), and Cs2CO3 (222 mg, 0.682 mmol) were combined in a flask and degassed with argon. To this solid mixture was added dioxane (2.0 mL), and the resulting mixture was degassed with argon for 5 min. The reaction mixture was heated to 110° C. for 1.5 h. The reaction was cooled to ambient temperature, then diluted with saturated aqueous NaCl and EtOAc. The layers were separated, and the aqueous layer was extracted with EtOAc. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The resulting crude product was purified by column chromatography on silica (10-30% EtOAc/hexanes gradient) to afford racemic methyl-4-(5-{3-[(5-fluoro-4-methylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-4-hydroxy-2,2-dimethylcyclohexanecarboxylate (143 mg, 0.295 mmol, 86% yield). MS ESI: [M+H]+ m/z 485.

1. customdegassed with argon
2. additionTo this solid mixture was added dioxane (2.0 mL)
3. customthe resulting mixture was degassed with argon for 5 min
4. temperatureThe reaction was cooled to ambient temperature
5. additiondiluted with saturated aqueous NaCl and EtOAc
6. customThe layers were separated
7. extractionthe aqueous layer was extracted with EtOAc
8. dry with materialThe combined organic layers were dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe resulting crude product was purified by column chromatography on silica (10-30% EtOAc/hexanes gradient)