Preparation method for vinorelbine tartrate

A technology of vinorelbine tartrate and vinorelbine, which is applied in the field of preparation of vinorelbine tartrate, can solve the problems of high price of dehydrated vinblastine, high industrial cost, and difficult control, and achieve easy control of the operation process, low cost, The effect of less side effects

Active Publication Date: 2011-09-28
HUBEI HONCH PHARMA
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Among the above four synthetic methods, the first method has fewer synthetic steps, mild conditions and few side reactions, but the reaction starting material dehydrated vinblastine is expensive and the cost is higher
The second and third methods also use dehydrated vinblastine as a starting material, the industrial cost is high, and there are many side reactions in the reaction process, which are difficult to control
Although the fourth method uses vinblastine sulfate, which is cheaper than dehydrated vinblastine, as the starting material, the first step is dehydrated with DMF to form dehydrated vinblastine, but the subsequent synthesis steps are similar to the second method, and there is also a reaction There are many side reactions in the process, and the disadvantages are not easy to control

Method used

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  • Preparation method for vinorelbine tartrate
  • Preparation method for vinorelbine tartrate
  • Preparation method for vinorelbine tartrate

Examples

Experimental program
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Effect test

Embodiment 1

[0035] (1) Synthesis of vinblastine-N oxide

[0036] Take 70g of vinblastine tartrate, put it in a three-necked flask, add 2L of distilled water, stir to make it completely dissolved, then add 350ml of ammonia water and stir, extract with dichloromethane, separate the organic layer, take 23g of m-chloroperoxybenzoic acid and slowly add In the above-mentioned organic layer, after stirring at room temperature until the reaction is complete, add 1300ml 10% sodium carbonate solution (the purpose of adding sodium carbonate solution is to make the precipitation completely separate out, generally get final product with 5%~20% sodium carbonate solution), Stir, filter, and vacuum-dry to obtain 38 g of vinblastine-N oxide with a purity of 98.6% and a yield of 54% (calculated as vinblastine tartrate).

[0037] (2) Synthesis of Dehydrovinblastine

[0038]Get the vinblastine-N oxide 38g and 49.0g Wenduolin that step (1) makes, put in the three-necked reaction bottle, add methylene chlorid...

Embodiment 2

[0076] (1) Synthesis of vinblastine-N oxide

[0077] Take 68g of vinblastine tartrate, put it in a three-necked flask, add 2L of distilled water, stir to make it completely dissolved, then add 350ml of ammonia water and stir, extract with dichloromethane, separate the organic layer, take 22g of m-chloroperoxybenzoic acid and slowly add In the above organic layer, after stirring at room temperature to complete the reaction, add 1500ml of 5% sodium carbonate solution, stir, filter, and vacuum-dry to obtain 37.5g of vinblastine-N oxide with a purity of 98.8% and a yield of 55%. (calculated as vinblastine tartrate).

[0078] (2) Synthesis of Dehydrovinblastine

[0079] Get vinblastine-N oxide 37.5g and 49.2g pendolin that step (1) makes, put in the three-necked reaction bottle, add 400ml of dichloromethane, stir and fully react at room temperature, then move into the ultra-low temperature cold bath, Observe that the temperature in the bottle reaches -91°C, slowly add 60ml of tri...

Embodiment 3

[0085] (1) Synthesis of vinblastine-N oxide

[0086] Take 72g of vinblastine tartrate, put it in a three-necked flask, add 2L of distilled water, stir to make it completely dissolved, then add 350ml of ammonia water and stir, extract with dichloromethane, separate the organic layer, take 25g of m-chloroperoxybenzoic acid and slowly add In the above-mentioned organic layer, after stirring and reacting completely at room temperature, add 1000ml 20% sodium carbonate solution, stir, filter, vacuum-dry, obtain 40g vinblastine-N oxide compound, purity 98.6%, yield is 55.6% (with vinblastine tartrate).

[0087] (2) Synthesis of Dehydrovinblastine

[0088]Get 40g of vinblastine-N oxide and 51g of Vindolin prepared in step (1), put them in a three-necked reaction bottle, add 400ml of dichloromethane, stir and fully react at room temperature, then move into an ultra-low temperature cold bath, observe the bottle When the internal temperature reaches -90°C, slowly add 65ml of trifluoroa...

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Abstract

The invention discloses a preparation method for vinorelbine tartrate; the preparation method comprises the following steps of: taking tartrate vinblastine as a starting material; using ammonia water for dissociating the starting material, reacting the dissociated starting material with the metachloroperbenzoic acid so as to obtain vinblastine-N oxide, then reacting the vinblastine-N oxide with vindoline and trifluoroacetic anhydride, carrying out the reduction through sodium borohydride so as to obtain dehydrated vinorelbine, treating the dehydrated vinorelbine so as to obtain vinorelbine, and finally salifying the vinorelbine with tartaric acid so as to obtain the vinorelbine tartrate. The preparation method has the advantages of low cost, few side reaction, easily controlled operation process, higher yield and product purity and wide industrialized application prospect.

Description

technical field [0001] The invention relates to a preparation method of vinorelbine tartrate, which belongs to the field of chemical pharmacy. Background technique [0002] Vinorelbine tartrate is a cell cycle-specific broad-spectrum antineoplastic drug. Its trade name is Navelbing. It was developed by the French company Pieer Fabre and first listed in France in 1989. It was launched in my country in 1993. Approved for import. [0003] The synthetic method of the vinorelbine tartrate of bibliographical report mainly contains following four kinds at present: [0004] (1) Dehydrated vinblastine is oxidized by m-chloroperoxybenzoic acid (MCPBA) to obtain vinblastine-N oxide, then treated with trifluoroacetic anhydride to open the ring, and then rearranged in the presence of water to obtain vinorelbine , and finally salted with tartaric acid to obtain vinorelbine tartrate. [0005] (2) Dehydrated vinblastine is chlorinated by N-chlorobenzotriazole, and the resulting 6'-chlorin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D519/04C07C59/255C07C51/41
Inventor 何福彪
Owner HUBEI HONCH PHARMA
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