Preparation method for vinorelbine

A technology of vinorelbine and dehydrated vinblastine, which is applied in the field of pharmaceutical preparation, can solve the problems of high price of silver tetrafluoroborate reagent, long process flow, complicated operation and the like, and achieves broad industrial application prospect, shortened process flow and preparation technology. optimized effect

Active Publication Date: 2011-01-26
GUANGZHOU HANFANG PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] The process is long, the operation is cumbersome, the silver tetrafluoroborate reagent is expensive, tetrahydrofuran is a kind of dangerous goods, and the consumption is large, and it is difficult to recycle.

Method used

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  • Preparation method for vinorelbine
  • Preparation method for vinorelbine

Examples

Experimental program
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Effect test

Embodiment 1

[0020] Under nitrogen protection, 10g of dehydrated vinblastine (purity 90.3% HPLC) was dissolved in 100ml of dichloromethane, cooled to -65°C, slowly added 2ml of trifluoroacetic acid, 50ml of dichloromethane and 2.3g of N-bromobutylene The solution composed of imide was added and reacted below -70°C for 2 hours (thin-layer chromatography showed that the starting material disappeared). Add 60ml of saturated sodium bicarbonate solution, stir evenly, let stand to separate layers, extract the aqueous layer twice with dichloromethane (25ml×2), combine the organic phases, wash with 30ml of water, and concentrate under reduced pressure to obtain bromide concentrate .

[0021] Put the bromide concentrated solution on the alumina column (the amount of alumina is 200g), use dichloromethane-methanol gradient elution, thin-layer chromatography (chloroform: methanol = 95: 5) monitoring, collect vinorelbine-containing fractions, after merging Concentrate under reduced pressure to obtain ...

Embodiment 2

[0023] 48.5g dehydrated vinblastine purity (91.36%), 485ml dichloromethane were added in the reaction flask, stirred and dissolved under nitrogen protection, cooled to -65°C, slowly added 5ml trifluoroacetic acid, 300ml dichloromethane and 11g N -A solution composed of bromophthalimide was added and reacted below -70°C for 2 hours (thin-layer chromatography showed that the raw materials disappeared). Add 500ml of saturated sodium bicarbonate solution, stir evenly, let stand to separate layers, extract the aqueous layer twice with dichloromethane (100ml×2), combine the organic phases, wash with 200ml of water, and concentrate under reduced pressure to obtain bromide concentrate .

[0024] Put the concentrated bromide solution on an alumina column (amount of alumina is 1500g), elute with dichloromethane-methanol gradient, monitor by thin-layer chromatography, collect vinorelbine-containing fractions, combine and concentrate under reduced pressure to obtain 42.6g vinorelbine Bin...

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Abstract

The invention discloses a preparation method of vinorelbine. The method comprises the following steps: taking anhydrovinblastine as a raw material; performing a bromination reaction to prepare bromide; and then performing separation by alumina column chromatography. The bromide is condensed and cyclized to vinorelbine during a column chromatographic separation process without using silver tetrafluoroborate and tetrahydrofuran, and product purity can be up to 65% (HPLC). The method helps avoid using the expensive silver tetrafluoroborate reagent, shorten process flow, lower raw material cost and reduce environmental pollution; meanwhile, the method also helps solve the disadvantages of unstable product quality, yield and the like in a silver tetrafluoroborate process and has good popularization and application prospect.

Description

technical field [0001] The invention relates to the technical field of medicine preparation, in particular to a new technology for the preparation of vinorelbine. Background technique [0002] Vinorelbine is a semi-synthetic vinblastine alkaloid antitumor drug. Compared with vinblastine, vincristine and vindesine, vinorelbine has lower neurotoxicity and stronger antitumor activity. At present, there are many methods for synthesizing vinorelbine, but due to the complex structure of vinorelbine, these methods all have problems such as long process flow, many types of chemical reagents used, large consumption, low yield and high cost. [0003] Vinorelbine and its tartrate are generally prepared from dehydrated vinblastine through processes such as halogenation, ring shrinkage, and salt formation. At -78°C, dehydrated vinblastine reacted with N-bromosuccinimide to obtain bromide, and then treated with silver tetrafluoroborate and water to obtain vinorelbine, which was then sepa...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D519/04B01D15/34
Inventor 林英昌冯锦玲罗春李灼涛
Owner GUANGZHOU HANFANG PHARMA
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