反应详情

A 10 mL round-bottomed flask was charged with 2-cyclopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.12 g, 0.36 mmol), (R)-2-amino-3,3-dimethyl-1-(pyrrolidin-1-yl)butan-1-one hydrochloride (137 mg, 0.53 mmol), HOBt (61 mg, 0.40 mmol) and EDC (76 mg, 0.40 mmol). Then added DMF (1.6 mL) followed by N,N-diisopropylethylamine (0.16 mL, 0.92 mmol). The light yellow reaction mixture was stirred at room temperature overnight then quenched with water and extracted with diethyl ether (2×50 mL). The combined organic layers were washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatography over 8 g SiO2 with EtOAc/hexanes (gradient: 0-60% EtOAc) to afford 195 mg of (R)-2-cyclopropyl-N-(3,3-dimethyl-1-oxo-1-(pyrrolidin-1-yl)butan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide as a viscous yellow oil.

1. customthen quenched with water
2. extractionextracted with diethyl ether (2×50 mL)
3. washThe combined organic layers were washed twice with water and once with brine
4. dry with materialthen dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified by chromatography over 8 g SiO2 with EtOAc/hexanes (gradient: 0-60% EtOAc)