反应详情

温度

25 °C

In a round bottom flask under argon was placed 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4,4,4-trifluoro-butyric acid (144 mg, 0.41 mmol) and 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49, 97 mg, 0.49 mmol) in N,N-dimethylformamide (4 mL). To this mixture was added N,N-diisopropyethylamine (200 μL, 1.23 mmol) and (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (271 mg, 0.62 mmol) and stirred for 16 h at 25° C. After this time, the mixture was diluted with ethyl acetate (25 mL) and washed with a saturated aqueous solution of ammonium chloride (25 mL), saturated aqueous solution of sodium bicarbonate (25 mL) and a saturated aqueous solution of sodium chloride (25 mL), dried over sodium sulfate, and then concentrated with silica gel (2 g). Purification by Biotage flash chromatography (Aspire 40 g column, 80% ethyl acetate) afforded 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1-H-pyrazol-3-yl]-4,4,4-trifluoro-butyramide (168 mg, 77%) as a white foam: HR-ES-MS m/z calculated for C23H24N4O5ClF3 [M+H]+ 529.1460, observed 529.1457.

1. customIn a round bottom flask under argon was placed
2. washwashed with a saturated aqueous solution of ammonium chloride (25 mL), saturated aqueous solution of sodium bicarbonate (25 mL)
3. dry with materiala saturated aqueous solution of sodium chloride (25 mL), dried over sodium sulfate
4. concentrationconcentrated with silica gel (2 g)
5. customPurification by Biotage flash chromatography (Aspire 40 g column, 80% ethyl acetate)