Method for preparing sugammadex sodium and sugammadex sodium intermediate

A technology of sugammadex sodium and intermediates, which is applied in the field of preparation of pharmaceutical compounds, can solve problems such as high cost, difficult operation, and large pollution, and achieve the effects of environmentally friendly synthesis methods, reduced production costs, and convenient production operations

Inactive Publication Date: 2019-06-14
陈文辉
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0015] The inventor has conducted research on the methods disclosed above, and found that the main disadvantage

Method used

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  • Method for preparing sugammadex sodium and sugammadex sodium intermediate
  • Method for preparing sugammadex sodium and sugammadex sodium intermediate
  • Method for preparing sugammadex sodium and sugammadex sodium intermediate

Examples

Experimental program
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Example Embodiment

[0055] Example 1

[0056] Preparation of Sodium Gluconate

[0057] The first step: the key intermediate 6-deoxy-6-perbromo-γ-cyclodextrin

[0058] Under the protection of nitrogen, 4kg of dimethylformamide, 1.5kg of γ-cyclodextrin (dried at 105°C) and 5.0kg of triphenylphosphine were added to the 50L reactor in sequence. The reaction system was cooled to 0-5°C, and 3.5kg of dibromohydantoin DMF solution was added dropwise. The temperature during the dropping process was controlled to be ≤60°C. After the addition, the reaction system was heated to 75-90°C, and the reaction was stirred for 4 hours.

[0059] After the reaction is complete, the system is cooled to room temperature, transferred to a 100L enamel reactor, 2.0kg methanol is added, the reaction system is cooled to room temperature, and the pre-configured sodium hydroxide aqueous solution is added dropwise to adjust the pH to 8-10; then water is added dropwise 30kg, after dropping, stirring at room temperature and temperature ...

Example Embodiment

[0068] Example 2

[0069] Preparation of key intermediate 6-deoxy-6-perbromo-γ-cyclodextrin (formula II)

[0070] Under the protection of nitrogen, 400ml of dimethylformamide, 150g of γ-cyclodextrin (not dried) and 550g of triphenylphosphine were added to the 5L reaction flask in sequence. The temperature of the reaction system was lowered to 0-5°C, 400g of dibromohydantoin DMF solution was added dropwise, the temperature during the dropping process was controlled to be ≤60°C, and the addition was completed, the reaction system was heated to 75-90°C, and the reaction was stirred for 4h.

[0071] After the reaction is completed, the system is cooled to room temperature, transferred to a 5L glass reactor, 200g methanol is added, the reaction system is cooled to room temperature, and the pre-configured sodium hydroxide aqueous solution is added dropwise to adjust the pH to 10; then 3.0kg of water is added dropwise, After the addition, the temperature was controlled and stirred at room ...

Example Embodiment

[0072] Example 3

[0073] Preparation of key intermediate 6-deoxy-6-perbromo-γ-cyclodextrin (formula II)

[0074] Under the protection of nitrogen, 50ml of dimethylformamide, 15g of γ-cyclodextrin (not dried) and 500g of triphenylphosphine were added to the 500ml reaction flask in sequence. The reaction system was cooled to 0~5℃, and 350g of dibromohydantoin dimethylformamide solution was added dropwise. The temperature during the dropping process was controlled to ≤60℃. After the addition, the reaction system was heated to 75~90℃ and stirred Reaction 4h.

[0075] After the reaction, the system was cooled to room temperature, transferred to a 1L reaction flask, 30ml methanol was added, the reaction system was cooled to room temperature, and the pre-configured sodium hydroxide aqueous solution was added dropwise to adjust the pH to 10; then 300g of water was added dropwise, After finishing temperature control and room temperature stirring for 5 hours. After suction filtration, the ...

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Abstract

The invention relates to a method for preparing sugammadex sodium and a sugammadex sodium intermediate. The method comprises the following steps that a, gamma-cyclodextrin, a halogenating agent and triphenylphosphine react in N,N-dimethylformamide; after the reaction is completed, alkali is added into reaction liquid for regulating the pH value of the reaction liquid to reach a neutral state and then reach an alkaline state; then, water is added for separating out solid; filtering is performed; through pulping and washing, an intermediate of 6-deoxy-6-perhalogeno-gamma-cyclodextrin (2) is obtained; b, in an organic solvent, the formula (2) and 3-mercaptopropionic acid react under the alkaline condition to generate sugammadex sodium; c, the sugammadex sodium crude product is refined to obtain the sugammadex sodium.

Description

Technical field: [0001] The invention relates to a preparation method of a pharmaceutical compound, in particular to a method of high-purity sugammadex sodium and its intermediate. Background technique: [0002] Sugammadex Sodium (Sugammadex Sodium) chemical name, 6-full deoxy-6-full (2-carboxyethyl) thio-γ-cyclodextrin sodium salt, CAS number: 343306-79-6, molecular formula: C72H104Na8O48S8 , Molecular weight: 2178.01, is a chemically synthesized drug for rapid reversal of neuromuscular blockade caused by anesthetics rocuronium bromide and vecuronium bromide during surgery in adult patients. Sugammadex is a synthetic modified γ-cyclodextrin consisting of a lipophilic core and a hydrophilic outer end. Sugammadex, administered through intravenous injection, can significantly improve the recovery of muscle relaxation after surgery, and quickly reverse the neuromuscular blockade of steroidal muscle relaxants in a short period of time. The drug was launched in Europe in 2008 an...

Claims

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Application Information

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IPC IPC(8): C08B37/16
Inventor 陈文辉
Owner 陈文辉
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