反应详情

To a solution of (R)-3-amino-1-pyrrolidin-1-yl-butan-1-one trifluoroacetate (crude from step 2, 118 mg, 0.44 mmol) in DMF (2 mL) were added N,N-diisopropylethylamine (0.19 mL, 1.09 mmol), 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (100 mg, 0.22 mmol), and HATU (91 mg, 0.24 mmol). The reaction mixture was stirred at room temperature overnight then quenched with water and extracted with EtOAc (3×). The combined organics were washed with water (3×) and brine then dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography with 50% to 100% EtOAc/hexanes to afford 125 mg (96%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-3-oxo-3-pyrrolidin-1-yl-propyl)-amide as a white solid.

1. customthen quenched with water
2. extractionextracted with EtOAc (3×)
3. washThe combined organics were washed with water (3×) and brine
4. dry with materialthen dried over MgSO4
5. concentrationconcentrated
6. customThe residue was purified by silica gel chromatography with 50% to 100% EtOAc/hexanes