Amine alkoxy tripterine derivative as well as preparation method and application thereof
A technology of triptolide and amine alkoxy, which is applied in the field of amine alkoxy triptolide derivatives and preparation, and can solve the problems of poor solubility, high toxicity and the like
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Embodiment 1
[0033] Embodiment 1: the preparation general method of intermediate B
[0034] Tripterine (0.2 mmol) was stirred and dissolved in DMF (4 mL), followed by adding sodium bicarbonate (1.0 mmol) and R 3 -Br (0.1 mmol), stirred at room temperature for 12.0-48.0 hours, and monitored the reaction progress by TLC. After the reaction, add 1mol / L hydrochloric acid to quench, add deionized water, extract with ethyl acetate, wash the organic layers with saturated aqueous sodium chloride solution after combining, filter after drying with anhydrous sodium sulfate, and evaporate the filtrate to remove the solvent under reduced pressure. The residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 20 / 1); when the carboxyl terminal undergoes amidation reaction, stir and dissolve tripterine (0.2mmol) in DMF (4mL) , then add EDCI (1.0mmol), HOBT (1.0mmol) and amine compound (0.2mmol), and the remaining steps are the same as before; then the above-mention...
Embodiment 2
[0035] Embodiment 2: the preparation general method of intermediate D
[0036] Add tripterine (1.0mmol), anhydrous potassium carbonate (3.0mmol) and acetone (5mL) into the reaction flask, stir evenly and then add the corresponding dibromoalkane (3.0mmol) dropwise, after dropping, protect the mixture with argon Stir under reflux for 2.0 to 24.0 hours, and monitor the progress of the reaction by TLC. After the reaction is over, filter while hot, wash the filter cake with an appropriate amount of acetone, evaporate the filtrate to remove the solvent under reduced pressure, add deionized water to the residue, extract with dichloromethane, wash the organic layers with saturated aqueous sodium chloride solution, anhydrous sodium sulfate After drying and filtering, the filtrate was evaporated to remove the solvent under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate=15 / 1) to obtain intermediate D.
Embodiment 3
[0037] Embodiment 3: the preparation general method of amine alkoxy tripterine derivative (I)
[0038] Add intermediate D (1.0 equiv.), anhydrous potassium carbonate (1.5 equiv.), acetonitrile and organic amine compounds (1.5 equiv.) into the reaction flask, reflux and stir for 4.0 to 24.0 hours under the protection of argon, and monitor the reaction by TLC process. After the reaction was over, the solvent was evaporated under reduced pressure, dichloromethane was added to the residue, and washed successively with 5% aqueous sodium hydroxide solution, deionized water and saturated aqueous sodium chloride solution, and the organic layer was dried over anhydrous sodium sulfate and filtered, and the filtrate was The solvent was evaporated under reduced pressure, and the obtained crude product was separated and purified by thin layer preparation to obtain the corresponding amine alkoxytripterine derivative (I), with a yield of 40.0-80.0%. 1 It was confirmed by H-NMR and HR-MS tha...
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