反应详情

A 25 mL round-bottomed flask was charged with 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.20 g, 0.44 mmol), (S)-2-aminopropan-1-ol (0.10 ml, 1.31 mmol), HBTU (331 mg, 0.87 mmol), and HOBT (134 mg, 0.87 mmol). Then added DMF (1 mL) followed by N,N-diisopropylethylamine (0.31 mL, 1.75 mmol). The yellow reaction mixture was stirred at room temperature overnight then quenched with water and extracted with EtOAc (30 mL). The organic layer was washed once with saturated NaHCO3 and water. The combined aqueous layers were back extracted with EtOAc (25 mL). The combined organic layers was dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatography over SiO2 with EtOAc/hexanes (gradient: 0-100% EtOAc) to afford 149 mg (66%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1-methyl-ethyl)-amide as a white solid.

1. customthen quenched with water
2. extractionextracted with EtOAc (30 mL)
3. washThe organic layer was washed once with saturated NaHCO3 and water
4. extractionThe combined aqueous layers were back extracted with EtOAc (25 mL)
5. dry with materialThe combined organic layers was dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was purified by chromatography over SiO2 with EtOAc/hexanes (gradient: 0-100% EtOAc)