Reacción #47649

Ecuación de reacción

(S)-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)-1H-pyrazol-3-yl]-4-methoxy-butyramide

p-toluenesulfonic acid monohydrate

→

(S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-4-methoxy-butyramide

Rendimiento 92.8%

Disolventes

methanol

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroIn a round bottom flask under argon was placed
2. 2
   ConcentraciónAfter this time period, the mixture was concentrated in vacuo
3. 3
   Otropurified by AnaLogix IntelliFlash flash chromatography (4 g column, 100% ethyl acetate to 5% methanol/ethyl acetate)

Procedimiento

In a round bottom flask under argon was placed (S)-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)-1H-pyrazol-3-yl]-4-methoxy-butyramide (26 mg, 0.051 mmol) dissolved in methanol (3 mL). This mixture was treated with p-toluenesulfonic acid monohydrate (1.5 mg, 0.008 mmol) and stirred at 25° C. for 16 h. After this time period, the mixture was concentrated in vacuo and purified by AnaLogix IntelliFlash flash chromatography (4 g column, 100% ethyl acetate to 5% methanol/ethyl acetate) to afford (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-4-methoxy-butyramide (22 mg, 92%) as a light yellow foam: HR-ES-MS m/z calculated for C21H25N4O6Cl [M+H]+ 465.1536, observed 465.1536; 1H NMR (300 MHz, DMSO-d6) δ ppm 2.06 (br. s., 2H), 3.20 (s, 3H), 3.22-3.31 (m, 4H), 3.67-3.78 (m, 1H), 3.78-3.90 (m, 1H), 4.07 (dd, J=13.6, 3.9 Hz, 1H), 4.27 (d, J=18.4 Hz, 1H), 4.50 (d, J=18.4 Hz, 1H), 4.69 (t, J=5.4 Hz, 1H), 4.78 (s, 1H), 4.79-4.88 (m, 1H), 4.92 (d, J=5.4 Hz, 1H), 6.39 (d, J=2.1 Hz, 1H), 7.30-7.40 (m, 1H), 7.41-7.55 (m, 3H), 7.64 (d, J=7.2 Hz, 1H), 10.64 (s, 1H).

Fuente