反应详情

温度

80 °C

In a 40 ml vial containing 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-benzyl-pyrrolidin-3-yl)-amide (1.32 g, 2.49 mmol) was added a solution of 6-fluoro-1-methyl-3-tributylstannyl-1H-indazole (1.20 g, 2.73 mmol) in DMF (25 ml). The vial was backfilled with nitrogen and tetrakis(triphenylphosphine)palladium (0) (159 mg, 0.14 mmol) and copper (I) iodide (107 mg, 0.56 mmol) were added. Again the vial was backfilled with nitrogen, then sealed and the reaction mixture was stirred in a heating block at 80° C. for 4 h. The reaction mixture was cooled to room temperature diluted with EtOAc/hexanes (100/30 ml) and washed with water (100 ml). The aqueous layer was extracted with EtOAc/hexanes (100/30 ml). The combined organic layers were washed with brine then dried over MgSO4, filtered, and concentrated. The crude was purified by flash chromatography (120 g Analogix) with 20% to 100% EtOAc in hexanes. The approriate fractions were combined and concentrated to yield 1.02 g (62%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-benzyl-pyrrolidin-3-yl)-amide as a light yellow solid. LC-MS (M+H)+=600.

1. additionwere added
2. customsealed
3. temperatureThe reaction mixture was cooled to room temperature
4. washwashed with water (100 ml)
5. extractionThe aqueous layer was extracted with EtOAc/hexanes (100/30 ml)
6. washThe combined organic layers were washed with brine
7. dry with materialthen dried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customThe crude was purified by flash chromatography (120 g Analogix) with 20% to 100% EtOAc in hexanes
11. concentrationconcentrated