反応 #47458

ord-3ac484feb796401b98074e581068d685

反応条件

詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    洗浄washed with an ammonium chloride solution
  2. 2
    乾燥a saturated sodium bicarbonate solution, saturated sodium chloride solution and then dried over magnesium sulfate
  3. 3
    その他The solvents were evaporated
  4. 4
    その他the residue was purified by AnaLogix flash chromatography (Supelco Flash Column 23 g, 50% to 60% ethyl acetate/hexanes) which

実験手順

To a solution of 2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-(1-fluoro-cyclopentyl)-propionic acid (0.264 g, 0.71 mmol) in dry N,N-dimethylformamide (6 mL) was added 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49 0.170 g, 0.86 mmol), and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (0.470 g, 1.06 mmol). To this mixture was added N,N-diisopropylethylamine (0.282 g, 2.18 mmol) and the resulting mixture stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate and washed with an ammonium chloride solution, a saturated sodium bicarbonate solution, saturated sodium chloride solution and then dried over magnesium sulfate. The solvents were evaporated and the residue was purified by AnaLogix flash chromatography (Supelco Flash Column 23 g, 50% to 60% ethyl acetate/hexanes) which afforded 2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-3-(1-fluoro-cyclopentyl)-propionamide (0.330 g, 84%) as a light brown oil: 1H NMR (300 MHz, DMSO-d6) δ ppm 1.24 (s, 3H), 1.30 (s, 3H), 1.46-2.02 (m, 8H), 2.04-2.47 (m, 2H), 3.73 (dd, J=8.4, 6.0 Hz, 1H), 4.00 (dd, J=8.4, 6.5 Hz, 1H), 4.06-4.20 (m, 2H), 4.28-4.39 (m, 2H), 4.53 (d, J=18.7 Hz, 1H), 5.03 (s, 1H), 5.09 (dd, J=9.5, 4.4 Hz, 1H), 6.44 (d, J=2.1 Hz, 1H), 7.28-7.49 (m, 3H), 7.61 (s, 1H), 10.84 (s, 1H).

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US07741327B2uspto-grants-2010_06