反应详情

温度

120 °C

A mixture of (R)-tert-butyl 3-(4-amino-6-bromo-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (9) (375 mg, 0.70 mmol), methyl boronic acid (417 mg, 6.96 mmol), Pd2(dba)3 (64 mg, 0.07 mmol), tricyclohexyl phosphine (PCy3) (39 mg, 0.14 mmol) and K3PO43H2O (556 mg, 2.09 mmol) in toluene (10.0 mL) was sealed in microwave tube. The reaction was purged with N2 before heated at 120° C. by microwave for 30 min. Another portion of methyl boronic acid (417 mg, 6.96 mmol) was introduced and the reaction was continued for additional 30 min. After cooled down to r. t., the reaction mixture was partitioned between DCM and water. The layers were separated. The aqueous phase was extracted with DCM. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure to give the crude product which was purified by column chromatographic (silica gel, 50% ethyl acetate in a mixture of petroleum ether and DCM (1:1)) to afford (R)-tert-butyl 3-(4-amino-6-methyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (10) (286 mg, 70% yield) as a yellow oil. LC-MS (ESI): m/z (M+1) 486.3.

1. customwas sealed in microwave tube
2. customThe reaction was purged with N2
3. temperatureAfter cooled down
4. custom, the reaction mixture was partitioned between DCM and water
5. customThe layers were separated
6. extractionThe aqueous phase was extracted with DCM
7. washThe combined organic layers were washed with brine
8. dry with materialdried over Na2SO4
9. concentrationconcentrated under reduced pressure
10. customto give the crude product which
11. customwas purified by column chromatographic (silica gel, 50% ethyl acetate
12. additionin a mixture of petroleum ether and DCM (1:1))