Oxime-containing amino derivatives, pharmaceutical composition thereof, preparation method and use thereof
A technology of amino and drugs, applied in the field of medicine and chemical industry, can solve problems such as difficult chemical synthesis, complex molecular structure, and difficulty in large-scale production
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Embodiment 1
[0070] Example 1: 3,4,5-trifluoro-2[(3-methyl-5-iodo-2-pyridyl)amino]benzaldehyde (Compound 1) Preparation
[0071] Step 1), the preparation of 2,3,4,5-tetrafluorobenzoic acid methyl ester: 2,3,4,5-tetrafluorobenzoic acid (48.5g, 0.25mol) was dissolved in 130mL of anhydrous methanol, slowly Chlorotrimethylsilane (63 mL, 0.50 mol) was added dropwise. After the dropwise addition, reflux for 12h. Evaporate the solvent and excess trimethylchlorosilane under reduced pressure with a water pump to obtain a light yellow liquid, add 200mL of dichloromethane, and wash with 10% aqueous sodium hydroxide solution, extract the water layer with dichloromethane, combine the organic layers, and Dry overnight with anhydrous sodium sulfate. The next day, it was filtered, and the solvent was evaporated under reduced pressure to obtain a colorless liquid, methyl 2,3,4,5-tetrafluorobenzoate (30.52 g, 97.8%). 1 H-NMR (400MHz, CDCl 3 ) δppm: 7.65-7.60 (m, 1H), 3.97 (s, 1H).
[0072] Step 2), ...
Embodiment 2
[0079] Example 2: (R, E)-3,4,5-trifluoro-2-[(3-methyl-5-iodo-2-pyridyl)ammonia base]-O-(2,3-dihydroxypropyl)benzaldoxime (compound 2)
[0080] Step 1), (R,E)-3,4,5-trifluoro-2-[(3-methyl-5-iodo-2-pyridyl)amino]-O-[(2,2-methyl- The preparation of 1,3 dioxolane-4 base) methyl] benzaldehyde oxime: 3,4,5-trifluoro-2-[(3-methyl-5-iodo-2-pyridyl)amino] Benzaldehyde (0.4 g, 0.98 mmol) and (R)O-{3[(tert-butyl-dimethylsilyl)oxy]propyl}hydroxylamine (0.30 g, 2.05 mmol) were dissolved in 10 mL of absolute ethanol, Heat to reflux and react for 2h. The reaction system was directly mixed with crude silica gel, and a yellow solid was obtained by column chromatography, which was directly used in the next reaction, ESI-MS m / z: 521.1[M+1] + .
[0081] Step 2), (R,E)-3,4,5-trifluoro-2-[(3-methyl-5-iodo-2-pyridyl)amino]-O-(2,3-dihydroxypropyl ) Preparation of benzaldoxime: (R, E)-3,4,5-trifluoro-2-[(3-methyl-5-iodo-2 pyridyl)amino]-O-[(2,2 -Methyl-1,3-dioxolan-4-yl)methyl]benzaldehyde ox...
Embodiment 3
[0082] Example 3: (E)-3,4,5-trifluoro-2-[(3-methyl-5-iodo-2-pyridyl)ammonia base]--O-(2,3-dihydroxypropyl)benzaldehyde oxime (compound 3)
[0083] The method is the same as in Example 2 to obtain a pale yellow solid. 1 H-NMR (400MHz, DMSO-D 6 )δppm: 8.26-8.22 (m, 1H), 7.71 (s, 1H), 7.65-7.61 (m, 1H), 7.47-7.45 (m, 1H), 7.34-7.32 (m, 1H), 4.70 (br s , 2H), 4.18-4.15(m, 1H,), 4.03-4.01(m, 1H), 3.72-3.70(m, 1H), 3.38-3.34(d, 2H, J=5.6Hz), 2.26(s, 3H). ES I-MS m / z: 482.0[M+1] + .
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