Succinic acid amide derivative containing naphthalene ring, its preparation method and use
A compound, cycloalkyl technology, applied in the field of uric acid transporter 1 inhibitor, can solve problems such as fulminant hepatitis, allergy, allopurinol liver and bone marrow toxicity
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Embodiment 1
[0034] .
[0035] A. Synthesis of Compound IV-1
[0036] 3.14g (20mmol) of compound II-1 and 2.64g (20mmol) of compound III were dissolved in 50mL of dry THF, stirred under cooling in an ice-water bath, and 4.13g (20mmol) of dicyclohexylcarbodiimide (DCC) and 4- Dimethylaminopyridine (DMAP) 0.61 g (5 mmol), then stirred at room temperature until the reaction was detected by TLC (within 12 h). The reaction mixture was poured into 300 mL of ice water, stirred, using 100 mL × 3 CH 2 Cl 2 Extract, combine the extract phases, successively wash with 100mL of 1% dilute hydrochloric acid and 100mL of 5% brine, and dry over anhydrous sodium sulfate. The desiccant was removed by suction filtration, the filtrate was evaporated to dryness on a rotary evaporator, and the obtained residue was purified by column chromatography to obtain compound IV-1, a white solid, ESI-MS, m / z=294 ([M+Na] + ).
[0037] B. Synthesis of Compound V-1
[0038] Compound IV-14.06g (15mmol) was dissolved i...
Embodiment 2
[0043] .
[0044] A. Synthesis of Compound IV-2
[0045] 3.66g (20mmol) of compound II-2 and 2.64g (20mmol) of compound III were dissolved in 50mL of dry THF, stirred under cooling in an ice-water bath, and 4.13g (20mmol) of dicyclohexylcarbodiimide (DCC) and 4- Dimethylaminopyridine (DMAP) 0.61 g (5 mmol), then stirred at room temperature until the reaction was detected by TLC (within 12 h). The reaction mixture was poured into 300 mL of ice water, stirred, using 100 mL × 3 CH 2 Cl 2Extract, combine the extract phases, successively wash with 100mL of 1% dilute hydrochloric acid and 100mL of 5% brine, and dry over anhydrous sodium sulfate. The desiccant was removed by suction filtration, the filtrate was evaporated to dryness on a rotary evaporator, and the obtained residue was purified by column chromatography to obtain compound IV-2, ESI-MS, m / z=320 ([M+Na] + ).
[0046] B. Synthesis of Compound V-2
[0047] Compound IV-24.45g (15mmol) was dissolved in 30mL of anhydr...
Embodiment 3-12
[0053]
[0054] .
PUM
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