반응 #47301

반응 방정식

(S)-3-cyclopentyl-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]-propionamide

hydrochloric acid

→

(S)-3-cyclopentyl-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-propionamide

수율 64.9%

용매

ethyl acetate

tetrahydrofuran

반응 조건

후처리

1. 1
   세척washed with water
2. 2
   건조a saturated sodium chloride solution and dried over sodium sulfate
3. 3
   농축The organic layer was concentrated

실험 절차

A solution of (S)-3-cyclopentyl-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]-propionamide (prepared as in Example 87, 120 mg, 0.22 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 adjusted to neutral and 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)-3-cyclopentyl-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-propionamide (70 mg, 63%) as an off-white solid: HR-ES-MS m/z calculated for C24H28F2N4O5 [M+H]+ 491.2101, observed 491.2102; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.08 (br. s., 1H) 1.28 (br. s., 1H) 1.36-1.95 (m, 9H) 3.19-3.30 (m, 2H) 3.64-3.80 (m, 1H) 3.80-3.91 (m, 1H) 4.07 (dd, J=13.6, 3.9 Hz, 1H) 4.28 (d, J=18.7 Hz, 1H) 4.61 (d, J=18.7 Hz, 1H) 4.69 (t, J=5.6 Hz, 1H) 4.79 (dd, J=10.3, 4.8 Hz, 1H) 4.92 (d, J=5.4 Hz, 1H) 5.01 (s, 1H) 6.39 (d, J=2.1 Hz, 1H) 7.22-7.48 (m, 3H) 7.51 (d, J=2.1 Hz, 1H) 10.78 (s, 1H).

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