The preparation method of tropisetron hydrochloride

The technology for tropisetron hydrochloride and compound is applied in the field of preparation of tropisetron hydrochloride bulk drug, and can solve the problems of difficult completion of reaction, poor system solubility, inconvenient production and the like

Active Publication Date: 2021-09-10
ZEIN BIOTECHNOLOGY CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The main disadvantages of this process route are: when preparing indole-3-formyl chloride, the solubility of the system is relatively poor, and the reaction is difficult to complete; the use of n-butyllithium which is expensive and inflammable and explosive brings inconvenience to production, and there are serious safety hazard

Method used

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  • The preparation method of tropisetron hydrochloride
  • The preparation method of tropisetron hydrochloride
  • The preparation method of tropisetron hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] The synthesis of embodiment 1 indole-3-formyl chloride

[0030] At 15-30°C, add 125.9g of compound (II) (0.78mol) and N,N-dimethylformamide (400mL) into the reaction flask, stir to dissolve, slowly add thionyl chloride, and complete; room temperature React for 5 hours. The reaction solution was directly carried out to the next reaction without treatment.

Embodiment 2

[0031] Example 2 Synthesis of Tropisetron Hydrochloride (I)

[0032] Control the temperature at 10-30°C, add 100.0 g of compound (III) (0.71 mol) to the prepared indole-3-carbonyl chloride (Example 1), and stir for 8 hours.

[0033] Add ethyl acetate (600mL) to the reaction system and stir for 1 hour, filter with suction and wash the filter cake with a mixed solvent of N,N-dimethylformamide / ethyl acetate (2:3), and reduce the filter cake at 50 °C. After pressing and drying for 6 hours, 215.8 g of an off-white solid was obtained, with a yield of 95.0% and a purity of 99.47%.

Embodiment 3

[0034] The preparation of embodiment 3 tropisetron hydrochloride crude drug

[0035] Add 100 g of crude tropisetron hydrochloride, ethanol (505 mL), and water (35 mL) into the reaction flask, heat up and stir to dissolve, add activated carbon, heat to reflux and stir to react for 0.5 h, then heat filter. Collect the filtrate and add concentrated hydrochloric acid to adjust the pH to 2~3.

[0036] The reaction system was stirred and cooled to 0-20°C, filtered with suction, and the filter cake was dried under reduced pressure at 50°C for 10 hours to obtain 90.5 g of a white crystalline solid with a yield of 90.5% and a purity of 99.98%.

[0037] 1 H NMR (600 MHz, DMSO- d 6 ): δ 12.197 (s, 1H), 11.082 (s, 1H), 8.090 (d, J = 3.0Hz, 1H), 8.048 (d, J = 7.2 Hz, 1H), 7.547 (d, J = 7.2 Hz, 1H), 7.192~7.241 (m, 2H), 5.145~5.130 (t, J = 4.8 Hz s, 1H), 3.890 (s, 1H), 2.690~2.750 (m, 2H), 2.688 (d, J = 4.8 Hz s, 3H), 2.230~2.360 (m, 4H), 2.118 (d, J = 4.2 Hz s, 2H) ppm. 13 C NMR (15...

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Abstract

The invention discloses a preparation method of tropisetron hydrochloride (I). The preparation method comprises using an amide solvent as a solvent to obtain tropisetron hydrochloride through chlorination and esterification. The preparation method disclosed by the invention has the advantages of low cost, simple operation and large-scale production, which lays a solid foundation for the quality research of tropisetron hydrochloride crude drug and related preparations.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis, and in particular relates to a preparation method of a tropisetron hydrochloride crude drug. Background technique [0002] Tropisetron hydrochloride is a potent and selective 5HT 3 Receptor antagonist, developed by Novartis, was launched in the UK in 1992 under the trade name Navoban, which is used to prevent and treat nausea and vomiting caused by radiotherapy and chemotherapy. The drug has been marketed in dozens of countries around the world. At present, its indications have also been extended to the prevention and treatment of nausea and vomiting after radiotherapy and chemotherapy in children and the treatment of postoperative nausea and vomiting in adults. It has the advantages of good acceptance, small adverse reactions, etc. and is very convenient to use; it only needs to be injected slowly intravenously or infused before chemotherapy and radiotherapy. [0003] Patent US47896...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D451/12C07D209/42
CPCC07D209/42C07D451/12
Inventor 黄超民牟祥韩娟邓祥林雷海燕
Owner ZEIN BIOTECHNOLOGY CO LTD
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