反应详情

温度

0 °C

To a solution of the compound from Step C (9.42 g, 19 mmol) in anhydrous dichloromethane (285 mL) at 0° C. was added HBr (5.7 M in acetic acid, 20 mL, 114 mmol) dropwise. The resulting solution was stirred at 0° C. for 1 h and then at rt for 3 h, evaporated in vacuo and co-evaporated with anhydrous toluene (3×40 mL). The oily residue was dissolved in anhydrous acetonitrile (50 mL) and added to a solution of sodium salt of 4-chloro-1H-pyrrolo[2,3-d]pyrimidine [for preparation, see J. Chem. Soc., 131 (1960)] in acetonitrile [generated in situ from 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (8.76 g, 57 mmol) in anhydrous acetonitrile (1000 mL), and NaH (60% in mineral oil, 2.28 g, 57 mmol), after 4 h of vigorous stirring at room temperature]. The combined mixture was stirred at room temperature for 24 h, and then evaporated to dryness. The residue was suspended in water (250 mL) and extracted with EtOAc (2×500 mL). The combined extracts were washed with brine (300 mL), dried over Na2SO4, filtered and evaporated. The crude product was purified on a silica gel column (10 cm×10 cm) using ethyl acetate/hexane (1:3 and 1:2) as the eluent. Fractions containing the product were combined and evaporated in vacuo to give the desired product (5.05 g) as a colorless foam.

1. waitat rt for 3 h
2. customevaporated in vacuo and co-evaporated with anhydrous toluene (3×40 mL)
3. dissolutionThe oily residue was dissolved in anhydrous acetonitrile (50 mL)
4. stirringThe combined mixture was stirred at room temperature for 24 h
5. customevaporated to dryness
6. extractionextracted with EtOAc (2×500 mL)
7. washThe combined extracts were washed with brine (300 mL)
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. customevaporated
11. customThe crude product was purified on a silica gel column (10 cm×10 cm)
12. additionFractions containing the product
13. customevaporated in vacuo