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Preparation method of triamcinolone acetonide

A compound and solvent technology, applied in the field of chemical synthesis of medicines, can solve the problems of high price of tetraene acetate and high cost of triamcinolone acetonide, simplify the operation of multi-step protection and deprotection, shorten the synthesis route, The effect of improving yield and quality

Inactive Publication Date: 2014-12-24
江西赣亮医药原料有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The method exists that the price of starting raw material tetraenyl acetate is higher, and when 9 (11) position epoxy reaction, because the existence of acetate ester can be partially hydrolyzed in 21 positions, can have a strong impact on the yield and the quality of this step, cause The cost of triamcinolone acetonide prepared by this method remains high

Method used

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  • Preparation method of triamcinolone acetonide

Examples

Experimental program
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Embodiment 1

[0035]Take a three-necked reaction bottle, pass it into nitrogen protection, add 300ml of 2-picoline and 100g of prednisone acetate into the reaction bottle, stir at room temperature for 10-15min, cool down to -20°C, add pentachlorohydrin to the reaction solution in batches Phosphate 20g, stirred for 10-15min, then 20g of sulfur dioxide was introduced into the reaction bottle, the temperature was kept at -20-10°C, and the time was about 1.5-2h. Finally, 2500ml of water was slowly dropped into the reaction solution, filtered, washed with a small amount of water until neutral, and the solid was dried at 60°C to obtain 92g of compound II, namely 21-hydroxypregna-1,4,16(17)-tri En-3,11,20-trione 21-acetate, mass yield: 92%, HPLC purity: 98%.

[0036] Add 1000ml of acetone and 50g of compound II to the reaction bottle, dissolve under stirring at room temperature, add 10ml of formaldehyde, cool down to -10~-5°C, add potassium permanganate solution (weigh 24g of potassium permanganat...

Embodiment 2

[0044] Take a three-necked reaction flask, pass it through nitrogen protection, add 300ml of pyridine and 100g of prednisone acetate into the reaction flask, stir at room temperature for 10-15min, cool down to 15°C, add N-bromosuccinimide to the reaction solution 54g, stirred for 10-15min, put 20g of sulfur dioxide into the reaction flask, kept the temperature at 10-15°C, and took about 1.5-2h. 2500ml of water was slowly dropped into the solution, filtered, washed with a small amount of water until neutral, and the solid was dried at 60°C to obtain 95g of compound II, namely 21-hydroxypregna-1,4,16(17)-triene-3,11 , 20-triketone 21-acetate, mass yield: 95%, HPLC purity: 98%.

[0045] Add 1000ml of acetone and 50g of compound II to the reaction flask, dissolve under stirring at room temperature, add 15ml of acetic acid, cool down to 5-10°C, add potassium permanganate solution (weigh 24g of potassium permanganate into 600ml of water, heat up slightly to About 30°C, stir and dis...

Embodiment 3

[0053] Take a three-necked reaction bottle, pass it through nitrogen protection, add 400ml of diisopropylamine and 100g of prednisone acetate into the reaction bottle, stir at room temperature for 10-15min, cool down to -10°C, add N-chlorobutane di Imide 50g, stirred for 10-15min, passed 20g of sulfur dioxide into the reaction flask, kept the temperature below -10-5°C, and took about 1.5-2h. After completion, slowly drop 2500ml of water into the reaction solution, filter, wash with a small amount of water until neutral, and dry the solid at 60°C to obtain 94g of compound II, namely 21-hydroxypregna-1,4,16(17)- Triene-3,11,20-trione 21-acetate, mass yield: 94%, HPLC purity: 98%.

[0054] Add 1000ml of methyl ethyl ketone and 50g of compound II to the three-necked reaction flask, pass through nitrogen, dissolve under stirring at room temperature, add 8ml of formic acid, cool down to 10-15°C, add potassium chlorate solution (weigh 40g of potassium chlorate into 600ml of water, S...

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Abstract

The invention discloses a preparation method of triamcinolone acetonide. A compound I prednisone acetate which is taken as a starting material is subjected to a primary elimination reaction, an oxidation reaction, a condensation reaction, a reduction reaction, a secondary elimination reaction, a hydrolysis reaction, an epoxidation reaction and a fluorination reaction, so that an end-product IX, 9-fluoro-11beta, 21-dihydroxyl-16a,17-[(1-methyl ethylidene) bi(oxo)]-pregnen steroid-1,4-diene-3, 20-diketone, namely triamcinolone acetonide, is obtained. The preparation method of the triamcinolone acetonide has the advantages that a relatively cheap starting raw material is adopted, each reaction step can be relatively easily realized, and yield is relatively high, so that production is more economic and safer, and the triamcinolone acetonide is more applicable to industrial production; a multi-step protection and deprotection operation is simplified, a synthetic route is greatly shortened, and production cost is reduced; possibility that a three-position carbonyl group is reduced in a reduction process is almost zero, so that side effects are greatly reduced, and yield and quality of the reduction reaction are improved.

Description

technical field [0001] The invention relates to a chemical synthesis method of medicine, in particular to a preparation method of triamcinolone acetonide. Background technique [0002] Triamcinolone acetonide (triamcinolone acetonide), English name Triamcinolone acetonide, chemical name: 9-fluoro-11β,21-dihydroxy-16a,17-[(1-methylethylene)bis(oxygen)]- Pregna-1,4-diene-3,20-dione is a common drug for skin diseases. It is mainly used for allergic and inflammatory diseases. Its effect is similar to that of hydrocortisone. It is suitable for external use of hydrocortisone For ineffective eczema, dermatitis and lesser psoriasis, the injection can be used for local injection of small lesions such as keloids, cystic acne, discoid lupus erythematosus, and alopecia areata; it can also be used for local injection in the joint cavity. [0003] The preparation of compound triamcinolone acetonide, present production technique mainly is through oxidation reaction, condensation reaction,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J71/00
Inventor 应正平蒋青锋杨坤何辉贤蒋华容张沙田
Owner 江西赣亮医药原料有限公司
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