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Preparation method of thiocolchicoside impurity

A technique for narcissin and impurities, which is applied in the field of preparation of thiocolchicine impurities, and achieves the effects of high purity of target product, simple operation method and high purity

Inactive Publication Date: 2018-11-23
TLC NANJING PHARMA RANDD CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The synthesis method of thiocolchicoside impurities has not been reported yet. In order to conduct comprehensive analysis and research on thiocolchicoside clinical, pharmacology, pharmacokinetics, and toxicology, it is necessary to design and develop thiocolchicoside impurities on the basis of existing technologies. The preparation method of colchicoside impurities provides a reference material for the comprehensive analysis of the clinical, pharmacology, pharmacokinetics and toxicology of thiocolchicoside

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0014] Preparation of intermediate product II: Dissolve 14g of thiocolchicoside in 700mL of dichloromethane and 14mL of triethylamine, add 0.6g of 4-dimethylaminopyridine and 15.2g of acetic anhydride, and react at 20°C for 16 hours. After spin-drying, 30 g of the product was obtained. Using dichloromethane:methanol at a volume ratio of 20:1 as the eluent, 16 g of yellow oil II was obtained by column chromatography with a yield of 91%.

[0015] The preparation of intermediate product III: get 12g intermediate product II and dissolve in tetrahydrofuran, add 1.6g 4-dimethylaminopyridine, 17.5g di-tert-butyl dicarbonate, 3.3g triethylamine, react at 20 ℃ for 16 hours, the reaction ends, the reaction After the solution was spin-dried, 25 g of crude product was obtained. Using dichloromethane:methanol at a volume ratio of 50:1 as the eluent, 13 g of brown oil III were obtained by column chromatography with a yield of 95%.

[0016] Preparation of intermediate product IV: Dissolve 13...

Embodiment 2

[0019] The preparation of intermediate product II: 15g thiocolchicoside is dissolved in 750mL dichloromethane and 8.5mL pyridine, add 0.65g 4-dimethylaminopyridine and 13.5g acetic anhydride, 20 ℃ of reaction 12 hours, reaction finishes, and reaction solution spins After drying, 35 g of the product was obtained. Using dichloromethane:methanol at a volume ratio of 20:1 as the eluent, 15 g of yellow oil II was obtained by column chromatography, with a yield of 84%.

[0020] The preparation of intermediate product III: get 10g intermediate product II and dissolve in tetrahydrofuran, add 1.34g 4-dimethylaminopyridine, 11.9g di-tert-butyl dicarbonate, 3.5gN, N-diisopropylethylamine, 20 ℃ reaction 18 After 1 hour, the reaction was completed, and the reaction solution was spin-dried to obtain 28 g of crude product. Using dichloromethane:methanol with a volume ratio of 50:1 as the eluent, 9 g of brown oil III were obtained by column chromatography, with a yield of 79%.

[0021] Prepar...

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PUM

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Abstract

The invention discloses a preparation method of a thiocolchicoside impurity and belongs to the field of drug synthesis, wherein the whole process design is reasonable, the operability is strong, and the purification is convenient. The thiocolchicoside is used as a starting material in the preparation method of thiocolchicoside impurity, the thiocolchicoside impurity is obtained by four-step reaction by synthesizing, optimal preparation step and reaction condition are selected through experiments, and the prepared thiocolchicoside impurity has a purity reaching 98% or above, provides test samples for the study of the thiocolchicoside, and has an important research value in clinical pharmacokinetics research.

Description

technical field [0001] The invention belongs to the field of drug synthesis, in particular to a method for preparing thiocolchicoside impurities. Background technique [0002] Thiocolchicoside, also known as 3-nor-thiocolchicine glucoside, is a glucoside extracted from the seeds of Colchicumautumnale, which has muscle relaxant, anti-inflammatory, analgesic and anesthetic properties. For the treatment of acute and chronic lumbar sciatica, cervical and brachial neuralgia, refractory torticollis, and post-traumatic and post-operative pain. [0003] With the progress of the times and the improvement of the level of science and technology, people have a fuller understanding of the importance of scientific evaluation of the quality, safety and efficacy of drugs before they are marketed. Among them, the quality of drugs is closely related to the quality of drugs. Impurity control. Impurities are often associated with drug safety and, in a few cases, potency. Therefore, the contr...

Claims

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Application Information

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IPC IPC(8): C07H15/248C07H1/00
CPCC07H1/00C07H15/248
Inventor 丁铜锁张东东胡永铸刘春崔希林
Owner TLC NANJING PHARMA RANDD CO LTD