Symmetrel derivatives and synthesis method thereof and their use as neuron damage protective agent
A technology of amantadine and its derivatives, which is applied to the preparation of amine active ingredients, carbamic acid derivatives, and medical preparations containing active ingredients, etc.
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Embodiment 1
[0043] Embodiment 1.1-methoxyacyl-3,5-dimethylamantadine (M 1-1 )Synthesis
[0044] Add triethylamine (0.24ml, 1.7mmol) to M 1 (300mg, 1.67mmol) in THF solution, after stirring for 10 minutes, ice-water bath and N 2 Under protection, methoxyl chloride (1.67 mmol) was added dropwise to the mixture, and stirred at room temperature for 3 hours. Filter the reaction solution, rinse the insoluble matter with THF, combine the filtrate, add 2 g of silica gel, stir for 40 minutes, evaporate the solvent and transfer to a silica gel column, wash with the eluent (haxane:EA=25:1), and concentrate the eluate 0.37 g of amide was obtained with a yield of 93%. The structural identification data are as follows:
[0045] m 1-1 : 1 HNMR (ppm, CDCl 3 ): 0.82 (s, 6H, 2CH 3 , 1.07(s, 2H, 4-CH 2 ), 1.2-1.5 (m, J=12, 4H, 7, 9-2CH 2 ), 1.5-1.6 (s, 4H, 2, 6-2CH 2 ), 1.75 (d, J=2.4, 2H, 10-CH 2 ), 2.08-2.10 (m, 1H, 8-CH), 3.6 (s, 3H, -OCH 3 ), 4.58(s, -NH).
[0046] FAB-MS: [2M + +1] 475.3...
Embodiment 2
[0047] Embodiment 2.N-methoxyacyl amantadine (Ad 1 )Synthesis
[0048] With the similar method with embodiment 1, synthetically obtains N-methoxyacyl adamantamine (Ad 1 ), the yield is 89%.
[0049] The structural identification data are as follows:
[0050] ad 1 : 1 HNMR (ppm, CDCl 3 ): 1.66 (m, 6H, 3CH 2 ), 1.9(m, 6H, 3CH 2 ), 2.09(m, 3H), 3.6(s, 3H, OCH 3 ).
[0051] FAB-MS: [M + +1] 210.1, mp: 90°C (crystal change), 112°C (melting).
Embodiment 3
[0052] Embodiment 3.N-isopropoxyacyl-3,5-dimethylamantadine (M 1-2 )Synthesis
[0053] With the similar method with embodiment 1, synthetically obtains M 1-2 , yield 79%. The structural identification data are as follows:
[0054] m 1-2 : 1 HNMR (ppm, CDCl 3 ): 0.82 (s, 6H, 2CH 3 ), 1.07 (d, J=1.8Hz, CH 2 ), 1.2(m, 6H, 2CH3), 1.1-1.4(m, 6H, 3CH 2 ), 1.6(m, 4H, 2CH2), 1.76(s, 2H, CH 2 ), 2.08-2.10 (m, 1H, CH), 4.42 (s, -NH), 4.83 (m, 1H, CH).
[0055] FAB-MS: [M + +1] 266.1.
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