Reaktion #2289931

Reaktionsgleichung

H2O

compound 20-3

ethyl trans-4-(4-((2-(3,5-dichloropyridin-4-yl)-2-oxoethyl)(3,5-difluorobenzyl)carbamoyl)-5-(difluoromethyl)-1H-pyrazol-1-yl)cyclohexanecarboxylate

HCl

→

compound

Ausbeute 62.0%

trans-4-(4-((2-(3,5-dichloropyridin-4-yl)-2-oxoethyl)(3,5-difluorobenzyl)carbamoyl)-5-(difluoromethyl)-1H-pyrazol-1-yl)cyclohexanecarboxylic acid

Ausbeute 62.0%

Lösungsmittel

dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction mixture was cooled to room temperature
2. 2
   Extraktionextracted with EtOAc (2×50 mL)
3. 3
   WaschenThe combined organic layers were washed with brine (2×10 mL)
4. 4
   Trocknendried over Na2SO4
5. 5
   Einengenconcentrated under reduced pressure
6. 6
   SonstigeThe residue was purified by reverse phase column chromatography (C18 silica gel, 75% CH3CN/water as eluent)

Vorschrift

To a solution of compound 20-3 (106 mg, 0.17 mmol) in dioxane (6 mL) was added 6 M HCl (6 mL) and heated at 80° C. for 16 h. The reaction mixture was cooled to room temperature, added H2O and extracted with EtOAc (2×50 mL). The combined organic layers were washed with brine (2×10 mL), dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by reverse phase column chromatography (C18 silica gel, 75% CH3CN/water as eluent) to provide the compound of example 20 (36 mg, 62%) as a white solid. 1H NMR (DMSO-d6) rotamers present δ 8.76 and 8.69 (2H, 2×s); 7.77 and 7.67 (1H, 2×s); 7.45-7.00 (4H, m); 4.91-4.70 (4H, m); 4.36-4.29 (1H, m); 2.31-2.24 (1H, m); 2.06-2.02 (2H, m); 1.94-1.89 (4H, m); 1.56-1.45 (2H, m); LCMS (ESI): 599 (M+H)+.

Quelle