反应详情

In a round-bottomed flask, [2-((R)-1-amino-ethyl)-oxazol-4-yl]-methanol trifluoroacetate (crude from Step 5) was dissolved in DMF (1.5 ml) and N,N-diisopropylethylamine (0.70 ml, 4.0 mmol) was added. Then 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (140 mg, 0.32 mmol was added followed by HATU (133 mg, 0.35 mmol). The reaction was stirred at room temperature overnight then quenched with water and extracted with diethyl ether (2×). The combined organic layers were washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-100% EtOAc) to afford 118 mg (66%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-hydroxymethyl-oxazol-2-yl)-ethyl]-amide as a light brown foam.

1. customthen quenched with water
2. extractionextracted with diethyl ether (2×)
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 chromatographed over silica gel with EtOAc/hexanes (gradient 0-100% EtOAc)