反应详情

温度

45 °C

To a stirred solution of N-cyano-2-phenyl-acetamide (35 mg, 0.2 mmol) (see Example 1) in DMF (1.25 mL), potassium tert-butoxide (0.22 mL of a 1.0 M THF solution, 0.22 mmol) was added, dropwise at 0° C., under nitrogen. Upon complete addition, the cooling bath was removed and the reaction was stirred for 0.5 h. After this time, the resulting anion was added dropwise to a stirred solution of the above 2-bromo-N-(2,2-dimethyl-propyl)-N-(2-morpholin-4-yl-2-oxo-ethyl)-acetamide (88 mg, 0.24 mmol) in DMF (1.25 mL) at room temperature, under nitrogen. Upon complete addition, the reaction was stirred at room temperature for 0.5 h, then warmed to 45° C. for 15 h. The reaction was cooled to room temperature and concentrated to dryness. The remaining residue was dissolved in EtOAc and washed with 5% citric acid (aqueous). The layers were separated and the aqueous phase was extracted with EtOAc (2×). The combined organics were dried (MgSO4), filtered and concentrated to give the crude product which was purified via reverse phase HPLC (C18 column, 20-100% CH3CN/H2O over 20 min at a flow rate of 20 mL/minute, UV detection was at 220 nm). Retention time of the product was 14.7 min. Product-containing fractions were concentrated to give 14 mg (15%) of the title compound.

1. additionUpon complete addition
2. customthe cooling bath was removed
3. additionUpon complete addition
4. stirringthe reaction was stirred at room temperature for 0.5 h
5. temperatureThe reaction was cooled to room temperature
6. concentrationconcentrated to dryness
7. dissolutionThe remaining residue was dissolved in EtOAc
8. washwashed with 5% citric acid (aqueous)
9. customThe layers were separated
10. extractionthe aqueous phase was extracted with EtOAc (2×)
11. dry with materialThe combined organics were dried (MgSO4)
12. filtrationfiltered
13. concentrationconcentrated
14. customto give the crude product which
15. customwas purified via reverse phase HPLC (C18 column, 20-100% CH3CN/H2O over 20 min at a flow rate of 20 mL/minute, UV detection
16. waitRetention time of the product was 14.7 min
17. concentrationProduct-containing fractions were concentrated