Реакция #47458

Уравнение реакции

2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-(1-fluoro-cyclopentyl)-propionic acid

1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine

Example 49

1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine

benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate

N,N-diisopropylethylamine

→

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

Выход 84.7%

Растворители

ethyl acetate

N,N-dimethylformamide

Условия реакции

Обработка

1. 1
   Промывкаwashed with an ammonium chloride solution
2. 2
   Сушкаa saturated sodium bicarbonate solution, saturated sodium chloride solution and then dried over magnesium sulfate
3. 3
   ДругоеThe solvents were evaporated
4. 4
   Другоеthe residue was purified by AnaLogix flash chromatography (Supelco Flash Column 23 g, 50% to 60% ethyl acetate/hexanes) which

Методика

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).

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