反应详情

n-BuLi (15.3 mL, 2.5 M in Hexane, 38.2 mmol) was added dropwise to a solution of 5-Bromo-4-chloro-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidine (10.0 g, 36.4 mmol) in Et2O (300 mL) at −78° C. and stirred for 1 h. 5-Bromo-N-methoxy-N-methyl-nicotinamide (8.9 g, 36.4 mmol) was added to the reaction mixture slowly and stirred for 3 h, warmed to room temperature, and stirred for an additional I h. The reaction mixture was quenched with saturated aqueous NH4Cl (200 mL) and stirred for 20 min. The aqueous layer was extracted with EtOAc (3×300 mL) and the combined organic layers were washed with brine (500 mL), dried (Na2SO4), filtered, and concentrated in vacuo to provide a crude brown solid. Trituration with 2-propanol provided the title compound as a pure off-white solid (7.0 g, 51%). MS: 380.7 (MH+); HPLC Rf: 5.5 min. (HPLC method 4).

1. stirringstirred for 3 h
2. stirringstirred for an additional I
3. customThe reaction mixture was quenched with saturated aqueous NH4Cl (200 mL)
4. stirringstirred for 20 min
5. extractionThe aqueous layer was extracted with EtOAc (3×300 mL)
6. washthe combined organic layers were washed with brine (500 mL)
7. dry with materialdried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customto provide a crude brown solid