反应详情

To a mixture of tert-butyl trans-3-{[(2-chloro-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy]methyl}-4-methylpyrrolidine-1-carboxylate (1.34 g, 2.7 mmol), 1-methyl-1H-pyrazol-4-amine (0.397 g, 4.05 mmol), Cs2CO3 (2.7 g, 8.4 mmol) and Xantphos (138 mg, 0.27 mmol) in 1,4-dioxane (30 mL) was added Pd2(dba)3 (247 mg, 0.27 mmol). The reaction was irradiated at 140° C. in three microwave tubes for 1 hr. TLC (petroleum ether/EtOAc=5:1) showed the reaction was complete. The mixture was concentrated and diluted with water (20 mL), then extracted with EtOAc (two×20 mL). The combined organic layers were washed with brine (four×20 mL), dried over Na2SO4 and concentrated. The residue was purified by Biotage flash chromatography (petroleum ether/EtOAc=1:1, Rf: 0.3) to yield the title compound (0.9 g, 59% yield) as a brown oil. m/z (APCI+) for C27H43N7O4Si 558.3 (M+H)+.

1. customThe reaction was irradiated at 140° C. in three microwave tubes for 1 hr
2. concentrationThe mixture was concentrated
3. additiondiluted with water (20 mL)
4. extractionextracted with EtOAc (two×20 mL)
5. washThe combined organic layers were washed with brine (four×20 mL)
6. dry with materialdried over Na2SO4
7. concentrationconcentrated
8. customThe residue was purified by Biotage flash chromatography (petroleum ether/EtOAc=1:1, Rf: 0.3)