Preparation method and medical application of unsaturated cyclic amine pyridine disulfide derivative
A kind of technology of pharmacy and compound, applied in the preparation field of above-mentioned compound, can solve the problems such as no literature report etc.
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Embodiment 1
[0105] Synthesis of 1-trityl-4-piperidone
[0106]
[0107] In a solution of 40 g (0.260 mol) of 4-piperidone-hydrate hydrochloride and 109 mL (0.78 mol) of triethylamine in 550 mL of dimethylformamide, under stirring at 60°C, add chlorotriphenyl After 72.5 g (0.260 mol) of methane, it was stirred at this temperature for 5 h, and after cooling, the precipitated triethylamine hydrochloride was filtered. The filtrate was poured into 2500 mL of water, stirred while pouring, and after standing still, it was filtered with suction to obtain 77.7 g of white solid, with a yield of 70.2%. 1 HNMR (500MHz, CDC1 3 ):d 7.86-7.06 (m, 15H, J = 6.5Hz), 2.64 (dd, 4H, J = 7.1Hz), 2.55 (dd, 4H, J = 7.1Hz). ESI-MS m / z 364.45 [M +Na] + .
Embodiment 2
[0109] Synthesis of Ethyl E-2-(4-carbonyl-1-tritylpiperidin-3-enyl)-acetate
[0110]
[0111] Put 60g (0.1757mol) of 1-trityl-4-piperidone and 15.8mL (0.1933mol) of pyrrolidine in 600mL of toluene solution, azeotrope under reflux for 3h with water separator, add glyoxylic acid after cooling down 20.2 mL (0.1933 mol) of ethyl ester, followed by azeotropic dehydration under reflux for 2 h. After cooling, 400 mL of water was added, extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to obtain 49.35 g of a light yellow oily substance, with a yield of 60.2%. 1 HNMR (500MHz, CDC1 3 ):d 7.51-7.17(m, 15H), 6.59(s, 1H), 4.10(q, 2H, J=7.1Hz), 3.71(s, 2H), 2.79(t, 2H, J=6.0Hz) , 2.65(s, 2H), 1.17(t, 2H, J=7.1Hz).
[0112] ESI-MS m / z 448.1[M+Na] +
Embodiment 3
[0114] Synthesis of E-2-(4-Hydroxy-1-tritylpiperidin-3-enyl)-ethyl acetate
[0115]
[0116] Dissolve 22g (0.0517mol) of E-2-(4-carbonyl-1-tritylpiperidin-3-enyl)-ethyl acetate in 50mL of dichloromethane, add 200mL of methanol, and After adding 2.34 g (0.0619 mol) of sodium borohydride little by little, the mixture was stirred at room temperature for 1 h. After concentrating the reaction solution under reduced pressure, 150 mL of water was added, extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to obtain light yellow oil M3-7, 12.8 g, yield 57.9%, 1 HNMR (300MHz, CDC1 3 ):d 7.45(d, 6H, J=7.3Hz), 7.25-7.11(m, 9H), 6.05(s, 1H), 4.48(s, 1H), 4.14-3.96(m, 3H), 2.99(s , 1H), 2.30-2.22(m, 1H), 2.10-2.03(m, 1H), 1.93-1.85(m, 3H), 1.12(t, 3H, J=7.1Hz). ESI-MS m / z426.2[M-H] - .
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