- Nicergoline synthesis method
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The invention belongs to the technical field of raw material medicine synthesis, and particularly relates to a nicergoline synthesis method, which comprises the following steps: (1) methylating nitrogen-hydrogen bonds in 10-methoxyl-methyl ergoate to obtain a; (2) reducing an ester group in a into a hydroxyl group to obtain b; and (3) acylating the hydroxyl in the b. The nicergoline synthesized by the synthesis method is high in purity, methyl ether impurities can be effectively avoided, reaction conditions are mild and controllable, industrial large-scale production of the nicergoline raw material medicine is facilitated, and the method plays a positive role in promoting improvement of the quality of the nicergoline raw material medicine and reducing side effects and risks of medication of patients.
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Paragraph 0010; 0044-0045; 0047-0048
(2021/10/11)
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- Improved preparation method of nicergoline (by machine translation)
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Compared the prior art,bromonicotinoyl chloride intermediate, is prepared-methoxyphenylglycinol :(1) by a reaction with an organic amine as, an acid-binding agent, to produce 10α -(2) methyl - 101010101010101010and X3B1,methoxyphenylglycinol, in a solvent, 10α - The final yield of the product can reach or above product to be 1 - suitable for large-scale ;(3) production, The, method 5 - comprises the following 5 - steps 5 - carrying out a methylation reaction 1 - with an organic, amine, as an organic amine as an acid,binding compound, in a solvent in a solvent and an inorganic base by an organic amine as an acid-binding agent in, an amide type non-protonic solvent to prepare 50% the . nylmyralyl chloride 99%, midst with an organic amine as an organic amine as an acid-binding agent. (by machine translation)
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Paragraph 0046; 0048; 0050; 0052; 0054; 0056; 0058; 0060
(2020/05/30)
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- Synthetic method of nicergoline
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The invention discloses a synthetic method of nicergoline. The synthetic method comprises the following steps: (1) photocatalytic addition reaction; (2) purification of 10-methoxy-dihydroergosterol; (3) methylation reaction; (4) purification of 10-methoxy-1, 6-dimethane-8-carbinol-ergoline; (5) esterification reaction; and (6) purifying of the nicergoline. According to the Synthetic method of thenicergoline, the mild photocatalytic addition, methylation and esterification reactions in the reaction process are adopted, and the raw materials and reagents with high safety are selected, so that the whole synthesis process is safe and controllable, the post-processing process is simplified, and the product obtained by the reaction is high in yield, high in purity, good in quality and suitablefor industrial production.
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Paragraph 0019; 0022-0023
(2020/05/30)
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- Novel preparation method of nicergoline
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The invention relates to a new preparation method of nicergoline. The method comprises the following steps: (1) adding an inorganic alkali into a polar aprotic solvent, and carrying out a methylationreaction on lysergol (II) and a methylation reagent to generate 1-methyl lysergol (III); (2) carrying out a light reaction on the 1-methyl lysergol (III) and methanol under the catalysis of concentrated sulfuric acid to prepare 1-methyl-10 alpha-methoxy dihydrolysergol (IV); and (3) in a polar aprotic organic solvent, carrying out a reaction on 5-bromonicotinic acid (V) and N,N'-carbonyl diimidazole by taking the N,N'-carbonyl diimidazole as a condensing agent to prepare a 5-bromo nicotinyl imidazole (VI) intermediate, and then carrying out a condensation reaction on the 5-bromo nicotinyl imidazole (VI) intermediate and the 1-methyl-10 alpha-methoxy dihydrolysergol (IV) to prepare nicergoline (I). Compared with the method in the prior art, the method of the invention does not require inertgas protection, is small in acid consumption, good in product quality, high in yield, easy in reaction byproduct recovery and utilization and suitable for industrial production.
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Page/Page column 5; 8-9
(2020/04/22)
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- Synthetic method for nicergoline
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The invention discloses a synthetic method for nicergoline. The synthetic method comprises the following steps: allowing lysergol and methanol to generate a methoxylation reaction, and carrying out purifying so as to obtain 10alpha-methoxyl-dihydrolysergol; allowing the 10alpha-methoxyl-dihydrolysergol and trimethylsulphoxonium iodide to generate a methylation reaction, and carrying out purifyingso as to obtain 1-methyl-10alpha-methoxyl-dihydrolysergol; and allowing the 1-methyl-10alpha-methoxyl-dihydrolysergol and 5-bromonicotinoyl chloride to generate an acylation reaction, and carrying outrefining so as to obtain the nicergoline. The synthetic method provided by the invention has the advantages of simple process, mild reaction conditions, easy operation, low toxicity of raw materials,high quality of a finished product, and facilitation of industrial popularization and application.
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Paragraph 0050; 0055
(2018/06/15)
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- Ergotine derivative and use thereof in prevention and treatment of mental diseases
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The invention discloses a nicergoline derivative, a preparation method thereof and application thereof in the field of medicines, belonging to the field of pharmaceutical chemical engineering. 10-methoxy ergot aldehyde or 10-methoxy ergot alcohol is taken as a key intermediate, nicergoline is taken as a matrix, and a C-8 site side chain of the matrix is modified; nicergoline is hydrolyzed into 10alpha-methoxy-1-methyl-9,10-dihydroergot alcohol and is oxidized into aldehyde, alcohol or aldehyde is derivatized to form a compound represented by formula I (shown in the description), and finally, the compound represented by formula I is subjected to activity screening.
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Paragraph 0015; 00116; 0017
(2017/07/22)
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- Drug-protein conjugates: Haptenation of 1-methyl-10α- methoxydihydrolysergol and 5-bromonicotinic acid to albumin for the production of epitope-specific monoclonal antibodies against nicergoline
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Two types of monoclonal antibodies were used for the determination of nicergoline in biological matrices. The antibodies were prepared with the hydrolysis products 5-bromonicotinic acid and 1-methyl-10α- methoxydihydrolysergol after hemisuccinoylation to haptens. The current amide bond-generating methods (mixed anhydride-, carbodiimide-, carbodiimide/sulfo- N-hydroxysuccinimide-, and dicyclohexylcarbodiimide/N-hydroxysuccinimide methods) were used in bovine serum albumin (BSA)-coupling techniques and yielded conjugates that were haptenated to varying extents. The conjugates exhibiting 23 mol of 1-methyl-10α-methoxydihydrolysergol (MMD) or 41 mol of 5-bromonicotinic acid (BNA) per mole of BSA were used for both immunization of mice and for coating the wells of the microtiter plates to select hybridomas and investigate specificity of the obtained antibodies. The results of hapten-inhibition ELISA using antigen-coated wells indicate that the supernatant of MMD-specific hybridoma exhibited 50% inhibition of antibody binding at 17 ± 2 μg of MMD and at 24.5 ± 2 μg of nicergoline, and the BNA-specific hybridoma exhibited similar inhibition at 147 ± 6 μg of BNA and 500 ± 30 μg of nicergoline. A main requirement for analytical purposes is that two different types of monoclonal antibodies recognize two different epitopes on nicergoline and its main metabolite, as shown by hapten-inhibition ELISA.
- Gabor,Hamilton,Pittner
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p. 1120 - 1125
(2007/10/03)
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