Reacción #47452

Ecuación de reacción

N,N-diisopropylethylamine

(S)-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid

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

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

→

(S)-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide

Rendimiento 75.0%

Disolventes

ethyl acetate

N,N-dimethylformamide

Condiciones de reacción

Tratamiento posterior

1. 1
   Lavadowashed with an ammonium chloride solution
2. 2
   Secadoa saturated sodium bicarbonate solution, saturated sodium chloride solution and then dried over magnesium sulfate
3. 3
   OtroThe solvents were evaporated
4. 4
   Otrothe residue was purified by AnaLogix flash chromatography (Teledyne Isco RediSep Flash Column 12 g, 100% ethyl acetate) which

Procedimiento

To a solution of (S)-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid (0.086 g, 0.28 mmol) in dry N,N-dimethylformamide (5 mL) was added 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49, 0.068 g, 0.34 mmol), and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (0.183 g, 0.41 mmol). To this mixture was added N,N-diisopropylethylamine (0.109 g, 0.85 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 (Teledyne Isco RediSep Flash Column 12 g, 100% ethyl acetate) which afforded (S)-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide (0.102 g, 75%) as a light yellow solid: 1H NMR (300 MHz, DMSO-d6) δ ppm 0.91 (t, J=7.2 Hz, 3H), 1.10-1.43 (m, 2H), 1.25 (s, 3H), 1.30 (s, 3H), 1.77 (q, J=7.7 Hz, 2H), 3.73 (dd, J=8.5, 6.0 Hz, 1H), 4.00 (dd, J=8.5, 6.3 Hz, 1H), 4.04-4.20 (m, 2H), 4.24-4.41 (m, 2H), 4.61 (d, J=18.7 Hz, 1H), 4.79 (t, J=7.7 Hz, 1H), 5.03 (s, 1H), 6.44 (d, J=2.1 Hz, 1H), 7.27-7.51 (m, 3H), 7.60 (d, J=2.1 Hz, 1H), 10.75 (s, 1H).

Fuente