Hydroxyquinoxalinecarboxamide derivative
A hydroxyl and alkyl technology, applied in the field of hydroxyquinoxaline formamide derivatives, can solve the problem that the structure of hydroxyquinoxaline is not disclosed or suggested
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Embodiment 1
[0527]
[0528] N-{(1S)-2-[4-(4-chlorophenoxy)piperidin-1-yl]-1-methyl-2-oxoethyl}-3-hydroxyquinoxaline-2- Formamide
Embodiment 1-1
[0530] [(1S)-2-(4-Hydroxypiperidin-1-yl)-1-methyl-2-oxoethyl]carbamate tert-butyl ester
[0531] At 0°C, under nitrogen flow, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.30g, 12.0mmol) and 1-hydroxybenzotriazole- Hydrate (1.84 g, 12.0 mmol) was added to a dichloromethane solution of 4-hydroxypiperidine (1.00 g, 10.0 mmol) and N-(tert-butoxycarbonyl)-L-alanine (1.89 g, 10.0 mmol) (50ml) followed by further addition of triethylamine (1.21ml, 12.0mmol) and stirring at room temperature overnight. The reaction solution was diluted with dichloromethane, then washed successively with saturated aqueous sodium bicarbonate solution, saturated aqueous ammonium chloride solution, water and brine, and then the resulting organic layer was dried over anhydrous sodium sulfate. The organic layer was concentrated and the resulting residue was purified by medium pressure preparative liquid chromatography (manufacturer Biotage, Inc., NH, 40+M) to give [(1S)-2-(4-hydroxypiperid...
Embodiment 1-2
[0535] {(1S)-2-[4-(4-Chlorophenoxy)piperidin-1-yl]-1-methyl-2-oxoethyl}carbamate tert-butyl ester
[0536] A solution of diisopropyl azodicarboxylate (2.80 ml, 5.21 mmol) in 40% toluene was added to [(1S)-2-(4-hydroxypiperidin-1-yl)- 1-Methyl-2-oxoethyl] tert-butyl carbamate (1.29g, 4.74mmol), 4-chlorophenol (670mg, 5.21mmol) and triphenylphosphine (1.37g, 5.21mmol) in toluene ( 18ml), stirred overnight at 90°C. The reaction solution was concentrated and the resulting residue was purified by medium pressure preparative liquid chromatography (manufacturer Biotage, Inc., 40+M) to give {(1S)-2-[4-(4-chlorophenoxy) Piperidin-1-yl]-1-methyl-2-oxoethyl}carbamate tert-butyl ester (700 mg, yield 34%), light yellow amorphous substance.
[0537] 1 H-NMR (CDCl 3 , 400MHz) δ: 7.25 (2H, d, J = 9.0Hz), 6.85 (2H, d, J = 9.0Hz), 5.55 (1H, d, J = 7.8Hz), 4.65 (1H, m), 4.52 ( 1H, m), 3.88-3.36(4H, m), 2.01-1.76(4H, m), 1.44(9H, s), 1.31(3H, d, J=7.0Hz).
[0538] MS (ESI, m / z): 383 (M+H) ...
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