Reacción #47296

Ecuación de reacción

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

hydrochloric acid

→

(S)-2-[4-(2,3-dichloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide

Disolventes

ethyl acetate

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Lavadowashed with water
2. 2
   Secadoa saturated sodium chloride solution and dried over sodium sulfate
3. 3
   ConcentraciónThe organic layer was concentrated

Procedimiento

A solution of (S)-2-[4-(2,3-dichloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide (prepared as in Example 79, 145 mg, 0.27 mmol) in tetrahydrofuran (20 mL) was treated with 2N aqueous hydrochloric acid (10 mL). The reaction mixture was stirred for 4 h at 25° C. The reaction mixture was diluted with ethyl acetate, washed with water, a saturated sodium chloride solution and dried over sodium sulfate. The organic layer was concentrated to afford (S)-2-[4-(2,3-dichloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide as a fluffy material. This material was dissolved in dichloromethane (20 mL) and treated with 1M hydrogen chloride in diethyl ether (2 mL). Solvents were evaporated and the residue was triturated with diethyl ether. The mixture was filtered to give (S)-2-[4-(2,3-dichloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide hydrochloride (85 mg, 59%) as a yellow solid: HR-ES-MS m/z calculated for C22H26Cl2N4O5 [M+H]+ 497.1353, observed 497.1355; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.90 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H), 1.35-1.66 (m, 2H), 1.67-1.86 (m, 1H), 3.19-3.38 (m, 2H), 3.70-3.93 (m, 2H), 4.09 (dd, J=13.4, 3.5 Hz, 1H), 4.16-4.32 (br. s., 2H), 4.23 (m, J=18.4 Hz, 1H), 4.62 (d, J=18.4 Hz, 1H), 4.82-4.91 (m, 1H), 4.92 (s, 1H), 6.41 (d, J=1.5 Hz, 1H), 7.42-7.59 (m, 3H), 7.64 (d, J=7.5 Hz, 1H), 10.79 (s, 1H).

Fuente