反应详情

A 25 mL round-bottomed flask was charged with 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (100 mg, 0.23 mmol), (S)-2-amino-4-(methylthio)butan-1-ol (32 mg, 0.24 mmol), and HATU (90 mg, 0.24 mmol). Then added acetonitrile (4 mL) followed by N,N-diisopropylethylamine (0.19 mL, 1.1 mmol). The reaction mixture was stirred at room temperature overnight then quenched with water. The mixture was extracted with ethyl acetate (3×). The organic layers were combined, dried over Na2SO4, and concentrated. The residue was purified by chromatography over SiO2 with EtOAc/heptanes (gradient: 5-50% EtOAc) to afford 105 mg (83%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1-hydroxymethyl-3-methylsulfanyl-propyl)-amide as an off-white foam. MS: [M+H]+=559.

1. customthen quenched with water
2. extractionThe mixture was extracted with ethyl acetate (3×)
3. dry with materialdried over Na2SO4
4. concentrationconcentrated
5. customThe residue was purified by chromatography over SiO2 with EtOAc/heptanes (gradient: 5-50% EtOAc)