反应详情

(R)-2-Amino-1-((S)-3-fluoro-pyrrolidin-1-yl)-propan-1-one trifluoroacetate (crude from Step 2) was dissolved in acetonitrile (4 ml) to which was then added 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (60 mg, 0.13 mmol), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (63 mg, 0.197 mmol) and N,N-diisopropylethylamine (0.092 ml, 0.52 mmol). The reaction was stirred at room temperature for 18 h and then water and ethyl acetate were added. The layers were separated and the aqueous layer was extracted once more with ethyl acetate. The combined organic layers were washed with sodium chloride solution and dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography (ethyl acetate/hexanes) to afford 55 mg (70%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-((S)-3-fluoro-pyrrolidin-1-yl)-1-methyl-2-oxo-ethyl]-amide. 1H NMR (300 MHz, CDCl3) δ: 9.29 (s, 1H), 8.88-8.93 (m, 1H), 8.85 (d, J=8.1 Hz, 1H), 8.32 (s, 1H), 7.43-7.46 (m, 1H), 7.35-7.39 (m, 1H), 5.70-5.74 (m, 2H), 5.21-5.26 (m, 1H), 4.15 (s, 3H), 3.61-4.00 (m, 5H), 3.54-3.61 (m, 2H), 2.06-2.46 (m, 2H), 1.59 (d, J=6.6 Hz, 3H), 0.90-0.97 (m, 2H), −0.05 (s, 9H).

1. customThe layers were separated
2. extractionthe aqueous layer was extracted once more with ethyl acetate
3. washThe combined organic layers were washed with sodium chloride solution
4. dry with materialdried over sodium sulfate
5. customAfter evaporation
6. customthe residue was purified by silica gel chromatography (ethyl acetate/hexanes)