反应详情

温度

0 °C

To an ice-cold solution of the product from Step C of Example 2 (1.57 g, 3.16 mmol) in CH2Cl2 (50 mL) was added HBr (5.7 M in acetic acid; 3.3 mL) dropwise. The reaction mixture was stirred at 0° C. for 1 h and then at room temperature for 2 h, concentrated in vacuo and co-evaporated with toluene (2×20 mL). The resulting oil was dissolved in MeCN (20 mL) and added dropwise to a solution of the sodium salt of 2-amino-4-chloro-5-methyl-1H-pyrrolo[2,3-d]pyrimidine in acetonitrile [generated in situ from 2-amino-4-chloro-5-methyl-1H-pyrrolo[2,3-d]pyrimidine [for preparation, see Liebigs Ann. Chem. 1984: 708-721] (1.13 g, 6.2 mmol) in anhydrous acetonitrile (150 mL), and NaH (60% in mineral oil, 248 mg, 6.2 mmol), after 2 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 (100 mL) and extracted with EtOAc (300+150 mL). The combined extracts were washed with brine (100 mL), dried over Na2SO4, filtered and evaporated. The crude product was purified on a silica gel column (5×7 cm) using ethyl acetate/hexane (0 to 30% EtOAc in 5% step gradient) as the eluent. Fractions containing the product were combined and evaporated in vacuo to give the desired product (0.96 g) as a colorless foam.

1. waitat room temperature for 2 h
2. concentrationconcentrated in vacuo and co-evaporated with toluene (2×20 mL)
3. dissolutionThe resulting oil was dissolved in MeCN (20 mL)
4. stirringThe combined mixture was stirred at room temperature for 24 h
5. customevaporated to dryness
6. extractionextracted with EtOAc (300+150 mL)
7. washThe combined extracts were washed with brine (100 mL)
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. customevaporated
11. customThe crude product was purified on a silica gel column (5×7 cm)
12. additionFractions containing the product
13. customevaporated in vacuo