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Budesonide preparing method

A technology for re-refining and compounding, applied in the field of preparation of budesonide raw materials, can solve the problems of cumbersome operation, unfavorable industrial production, severe reaction conditions, etc., and achieve the effects of mild reaction conditions, great application value, and simple operation.

Active Publication Date: 2015-11-18
SHANGHAI SINE PROMOD PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The above two preparation methods have problems such as harsh reaction conditions, high requirements on equipment, cumbersome operation, long working hours, low purity and low yield when preparing some intermediates, resulting in large environmental pollution, high cost, and Not conducive to industrial production

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Example 1: Preparation of 17,21-diacetoxy-1,4-pregnadiene-3,11,20-trione III

[0050]

[0051] Add 200 g (0.56 mol) of prednisone and 1 L of pyridine into a 3 L three-necked round-bottomed flask, stir to dissolve, add 150 mL of acetic anhydride, react at 85°C to 90°C for 2.5 hours, monitor the reaction by TLC until the reaction is complete. The reactant was poured into 10 L of ice water, left to solidify for 2.5 h, filtered with suction, washed with water, and dried to constant weight to obtain 243 g of intermediate compound III as a white solid, which was directly used in the next step. The yield was 98.4%, and the chemical purity by HPLC was 98.2%.

Embodiment 2

[0052] Example 2: Preparation of 21-acetoxy-1,4,16-pregnatriene-3,11,20-trione IV

[0053]

[0054] Add 240g (0.54mol) of 17,21-diacetoxy-1,4-pregnadiene-3,11,20-trione III, 120g of anhydrous sodium acetate and 1.5L of DMF into a 3L three-neck round bottom flask , under the protection of nitrogen, react at 95° C. to 100° C. for 4.5 h, and monitor the reaction by TLC until the reaction is complete. The reactant was poured into 15 L of ice water, allowed to stand for 3 hours to solidify, filtered with suction, washed with water, and dried to a constant weight to obtain 200 g of intermediate compound IV as a khaki solid, which was directly used in the next step. The yield was 96.4%, and the chemical purity by HPLC was 97.8%.

Embodiment 3

[0055] Example 3: Preparation of 16α, 17α-dihydroxy-21-acetoxy-1,4-pregnadiene-3,11,20-trione V

[0056]

[0057] Add 200g (0.52mol) of 21-acetoxy-1,4,16-pregnatriene-3,11,20-trione IV and 6L of acetone into a 10L stainless steel reaction tank, stir to dissolve, and control in an ice-water bath. The inner temperature is 0°C-5°C; 115g of potassium permanganate is firstly dissolved in 800mL of water, and in an ice-water bath, when the inner temperature is 0°C-5°C, add 800mL of frozen acetone and 50mL of frozen formic acid, and stir evenly; The potassium solution was added to the acetone solution of the intermediate compound IV, and the reaction was rapidly stirred at 0°C to 5°C for 7 minutes, and the reaction was quenched with 600 mL of 15% aqueous sodium sulfite solution, filtered with suction, the filter cake was washed with acetone, and the mother liquor was concentrated and evaporated to remove the acetone. A solid precipitated, filtered, washed the filter cake with water...

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Abstract

The invention discloses a budesonide preparing method. Prednisone I and acetic anhydride II react to produce 17,21-diacetoxy-1,4-pregnane diene-3,11,20-triketone III, the III is degreased in an anhydrous solvent to obtain 21-acetoxyl group-1,4,16-pregnane diene-3,11,20-triketone IV, the IV is oxidized to obtain 16alpha,17alpha-dyhydroxy-21-acetoxyl-1,4-pregnane diene-3,11,20-triketone V, the V and n-butyl aldehyde VI are condensed to obtain 16alpha,17alpha-22(R,S) propyl methylenedioxy-21-acetoxyl group-1,4-pregnane diene-3,11,20-triketone VII, the VII is reduced to obtain 16alpha,17alpha-22(R,S) propyl methylenedioxy-11beta-hydroxyl-21-acetoxyl group-1,4-pregnane diene-3,20-diketone VIII, the VIII is subjected to base catalysis to obtain budesonide IX. The budesonide preparing method is suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of medicine, in particular to a preparation method of budesonide raw material medicine. Background technique [0002] The chemical name of budesonide is: 16α,17α-22(R,S)propylmethylenedioxy-11β,21-dihydroxy-1,4-pregnadiene-3,20-dione, which The chemical structural formula is: [0003] [0004] Budesonide was developed by AstraZeneca Pharmaceutical Co., Ltd. and launched in 1981. It is an acetal non-halogenated glucocorticoid drug with strong anti-inflammatory effect, which can inhibit early bronchospasm and late allergic reaction. Its anti-inflammatory activity is 1,000 times that of hydrocortisone, stronger than beclomethasone dipropionate and other glucocorticoids, has a long acting time and rarely produces systemic side effects of adrenal corticosteroids, so it has a comparative advantage among similar drugs. High local / systemic effect ratio, more suitable for topical medication, with the character...

Claims

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Application Information

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IPC IPC(8): C07J71/00
CPCC07J71/0031
Inventor 胡林森肖志勇蒋俊刘斐李丁
Owner SHANGHAI SINE PROMOD PHARMA
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