反应详情

A solution of (R)-3-[(E)-3-(5-cyano-2-methoxy-phenyl)-acryloylamino]-4-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-butyric acid (0.1 g, 0.21 mmol) in DMF (1 ml) is treated with diisopropylethylamine (0.108 ml, 0.62 mmol) and 2-methylamino-ethanol (0.02 ml, 0.248 mmol). To the solution is added O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate (0.117 g, 0.31 mmol) and the reaction mixture stirred at room temperature for 1 hour. The reaction mixture is partioned between ethylacetate and saturated aqueous NaHCO3. The ethylacetate phase is washed with saturated brine, dried over MgSO4 and evaporated. The crude product is purified by flash silica chromatography (elution with 5:95 methanol/DCM) to afford (E)-3-(5-cyano-2-methoxy-phenyl)-.N.-((R)-2-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-1-{[(2-hydroxy-ethyl)-methyl-carbamoyl]-methyl}-ethyl)-acrylamide. [M-H] 537.02.

1. washThe ethylacetate phase is washed with saturated brine
2. dry with materialdried over MgSO4
3. customevaporated
4. customThe crude product is purified by flash silica chromatography (elution with 5:95 methanol/DCM)
5. customto afford (E)-3-(5-cyano-2-methoxy-phenyl)-.N