反应详情

(2R,5S)-4-Carboxymethyl-2-methyl-5-(2-oxo-pyrrolidin-1-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester (0.20 g, 0.56 mmol) and 6-(1,1-difluoro-propyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine (0.15 g, 0.6 mmol) were dissolved in DMF (2.8 mL). N,N-Diisopropylethylamine (0.36 g, 2.8 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.43 g, 1.1 mmol) were added and the reaction stirred at room temperature for 18 h. Saturated aqueous sodium bicarbonate (10 mL) was added and the aqueous phase extracted with EtOAc (3×10 mL). The combined organic extracts were diluted with petroleum spirit (20 mL), washed with water (3×), dried with sodium sulfate, filtered and concentrated. Chromatography (silica gel, gradient elution, 0-5%, methanol in EtOAc) gave the title compound (0.178 g), MS: [M+H]+=564.

1. extractionthe aqueous phase extracted with EtOAc (3×10 mL)
2. additionThe combined organic extracts were diluted with petroleum spirit (20 mL)
3. washwashed with water (3×)
4. dry with materialdried with sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. washChromatography (silica gel, gradient elution, 0-5%, methanol in EtOAc)