Preparation of desoximetasone

A technology of deoxymethasone and organic solvents, which is applied in the field of preparation of deoxymethasone, can solve the problems of low yield, long reaction route, and tediousness, etc., and achieve the effects of easy availability of raw materials, reduction of production costs and industrial conditions, and simple lines

Active Publication Date: 2011-05-04
TIANJIN PHARMA GROUP CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In summary, the synthetic method of dexamethasone is earlier, and there are deficiencies, the reaction route is longer, more cumbersome, and the yield is low, which restricts industrialization and cost control

Method used

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  • Preparation of desoximetasone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0069] epoxy reaction

[0070] Add 10g of 1,4,9,16-tetraene-pregna-3,20-dione (CN1896090), 120ml of acetone into the reaction flask, stir, cool down to 0°C, add 9g of NBS within 30 minutes, Keep the reaction at 5-10°C for 2 hours, add 10% sodium carbonate aqueous solution to neutralize to PH=6.5, raise the temperature to 20±2°C, add 10% sodium hydroxide aqueous solution 15ml within 1 hour, and control the temperature at 20-25°C After 2 hours of reaction, acetic acid was neutralized to PH=7, concentrated under reduced pressure until there was no smell of acetone, diluted into ice water, filtered, and dried to obtain 10.2 g of 9,11-epoxy-1,4,16-triene- Pregna-3,20-dione (1).

[0071] Grignard reaction

[0072] The configuration of the Grignard reagent: in 20ml of tetrahydrofuran, pass nitrogen, add 0.8g of magnesium strips, pass in methyl bromide gas, heat up and reflux for 0.5h, cool down for later use.

[0073] Add 60ml of tetrahydrofuran, 0.1g of ketone chloride and 10.2g ...

Embodiment 2

[0083] Iodine reaction:

[0084] Add 150ml of methanol and 6.1g of calcium oxide to the reaction bottle, and 8.5g of anhydrous calcium chloride in 90ml of methanol solution in another volumetric flask, take out 1 / 4 after dissolving, add to the reaction bottle, and dissolve the rest 15.0g of iodine particles, Add 10g of 1,4,9,16-tetraene-pregna-3,20-dione (CN1896090) into the reaction flask, fill with nitrogen, control the temperature at 0±5°C, add iodine solution dropwise, drop for about 3 hours Finished, after another 1 hour of reaction, the reaction solution was diluted in 600ml of 2% ammonium chloride aqueous solution, stirred for 1 hour, left to stand for 1 hour, filtered, washed with water to neutrality, and obtained wet product iodide (5). The product is unstable and does not need to be dried, and the storage time should not be too long, and it is ready for use.

[0085] Replacement reaction:

[0086] Add 40ml of DMF, 1ml of acetic acid, 0.8g of potassium acetate to th...

Embodiment 3

[0097] epoxy reaction

[0098] With the method of Example 1, 10g of 1,4,9,16-tetraene-pregna-3,20-dione (CN1896090) obtained 10.1g of 9,11-epoxy-1,4,16-trione En-pregna-3,20-dione (1).

[0099] Iodine reaction:

[0100] With the method of Example 1, 11.1g of 9,11-epoxy-1,4,16-triene-pregna-3,20-dione (1) was loaded with iodine to obtain wet product iodide 21-biiodo- 9,11-Epoxy-1,4,16-triene-pregna-3,20-dione (9).

[0101] Replacement reaction:

[0102] With the method of Example 1, the iodide was replaced to obtain 11.2g of 21-hydroxyl-9,11-epoxy-1,4,16-triene-pregna-3,20-diketone-21-acetate ( 10).

[0103] Grignard reaction

[0104] With the method of Example 1, 11.2g of 21-hydroxyl-9,11-epoxy-1,4,16-triene-pregna-3,20-diketone-21-acetate (10) Grignard obtained 10.7 g of 16α-methyl-9,11-epoxy-21-hydroxy-1,4-diene-pregna-3,20-dione-21-acetate (11).

[0105] ring opening reaction

[0106] With the method of Example 1, 10.7g of 16α-methyl-9,11-epoxy-21-hydroxyl-1,4-diene-...

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Abstract

The invention relates to a preparation method of a steroid compound, in particular to the preparation of desoximetasone, which takes 1, 4, 9, 16-arachidonic-pregna-3, 20-diketone (CN1896090) as the initiator and is improved by 16, 17-grignard, 9, 11th and 21st to obtain the desoximetasone and the 21st esterified ester thereof. The process has the advantages that, as the existing intermediate of the company is adopted as the initiator, the line is concise, the material is easy to obtain, expensive auxiliary materials are saved, and the yield and the cost are obviously superior to the historical synthetic method of the desoximetasone; in addition, the adoption of the existing intermediate realizes the doubling production of the dexamethasone products, betamethasone products and the desoximetasone products, thus greatly reducing the production cost and industrial conditions.

Description

technical field [0001] The present invention relates to a kind of preparation method of steroid compound, especially relates to the preparation of dexamethasone. Background technique [0002] Dexamethasone is a very useful class of glucocorticoid drugs, belonging to the topical application of corticosteroids, mainly used for the treatment of skin diseases, the literature J Int Med Res.1987 May-Jun; 15 (3): 160-6 pointed out that in For the treatment of eczema, the effect of 0.25% deoxymethasone ointment is better than that of 0.1% betamethasone valerate ointment, and the effect of 0.05% deoxymethasone ointment is equivalent to that of 0.1% betamethasone valerate ointment. Literature Clin Ther.1985; 8 (1): 118-25 pointed out: 0.25% deoxymethasone ointment and 0.05% Fuqingyi ointment are equally safe and effective in the treatment of psoriasis, but compared in effect, 0.25% deoxymethasone The effect of ointment is slightly better than that of 0.05% Fuqing ointment. [0003] ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J5/00
Inventor 李金禄吴雅琳
Owner TIANJIN PHARMA GROUP CORP
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