Reacción #47272

Ecuación de reacción

(S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-cyclohexyl-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1-H-pyrazol-3-yl]-propionamide

(S)-2-[4-(2-Chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-cyclohexyl-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1-H-pyrazol-3-yl]-propionamide

hydrochloric acid

→

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

Rendimiento 83.0%

Disolventes

ethyl acetate

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Lavadowashed with saturated sodium bicarbonate
2. 2
   Secadoa saturated sodium chloride solution and dried over magnesium sulfate
3. 3
   ConcentraciónUpon concentration

Procedimiento

A solution of ((S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-cyclohexyl-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1-H-pyrazol-3-yl]-propionamide (prepared in Example 62, 201 mg, 0.37 mmol) in tetrahydrofuran (6 mL) was treated with 1N aqueous hydrochloric acid (3 mL). The reaction mixture was stirred for 4 h at room temperature. The reaction mixture was diluted with ethyl acetate (60 mL), washed with saturated sodium bicarbonate, a saturated sodium chloride solution and dried over magnesium sulfate. Upon concentration afforded (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-cyclohexyl-N-[1-((R)-2,3-dihydroxy-propyl)-1-H-pyrazol-3-yl]-propionamide (153 mg, 83%) as a white powder: HR-ES-MS m/z calculated for C25H31ClN4O5, [M+H]+ 503.2056 observed 503.2056; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.81-1.02 (m, 2H), 1.02-1.29 (m, 4H), 1.52-1.83 (m, 7H), 3.18-3.32 (m, 2H), 3.70-3.93 (m, 2H), 4.09 (dd, J=13.6, 3.6 Hz, 1H), 4.19 (d, J=18.4 Hz, 1H), 4.59 (d, J=18.4 Hz, 1H), 4.71 (t, J=5.4 Hz, 1H), 4.80 (s, 1H), 4.85-4.92 (m, 1H), 4.94 (d, J=5.4 Hz, 1H), 6.40 (d, J=1.8 Hz, 1H), 7.37 (td, J=7.8, 1.5 Hz, 1H), 7.46 (t, J=7.2 Hz, 1H), 7.50-7.56 (m, 2H), 7.65 (d, J=7.8 Hz, 1H), 10.76 (s, 1H).

Fuente