Preparation method for finasteride intermediate

A technology of finasteride and intermediates, which is applied in the field of preparation of finasteride intermediates, can solve the problems of high cost, large pollution, long route and the like, and achieves the effects of low cost, high yield and abundant resources

Inactive Publication Date: 2015-12-02
湖北竹溪人福药业有限责任公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The above route utilizes dienolone acetate to synthesize finasteride, which has a long route, high cost and great pollution

Method used

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  • Preparation method for finasteride intermediate
  • Preparation method for finasteride intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] (1) Cyanide

[0023] Under the protection of nitrogen, add 20g of compound II and 40g of potassium tert-butoxide into 800g of ethylene glycol dimethyl ether and 240g of tert-butanol, and cool to -10°C while stirring; slowly add 30g of p-toluenesulfonylmethane After adding isocyanide, heat up to 20°C, stir for 4h, TLC until the raw material reacts completely; analyze with ice water, filter with suction to obtain an off-white solid, wash with water until neutral, dry at 55°C to constant weight, and obtain 18.5g of compound Ⅲ is 3-oxo-4-en-17-cyano;

[0024] (2) Amidation

[0025] Add 18.5g of compound III 3-oxo-4-en-17-cyano into the reaction flask, add 55.5g of glacial acetic acid, 27.8g of tert-butanol, stir well, slowly add 18.5g of sulfuric acid dropwise, and react at a temperature of 10°C for 15h. TLC monitored until the reaction was complete. Add 22.2g of sodium carbonate to terminate the reaction, add 278ml of water for water analysis, filter, wash the filter ca...

Embodiment 2

[0027] (1) Cyanide

[0028] Under the protection of nitrogen, add 50g of compound II and 150g of potassium tert-butoxide into 2250g of ethylene glycol dimethyl ether and 750g of tert-butanol, and cool to 0°C while stirring; slowly add 100g of p-toluenesulfonylmethyl After adding isocyanide, raise the temperature to 25°C, stir for 3 hours, TLC until the reaction of the raw materials is complete, analyze with ice water, filter with suction to obtain an off-white solid, wash with water until neutral, and dry at 60°C to constant weight to obtain 46 g of compound III. 3-oxo-4-en-17-cyano;

[0029] (2) Amidation

[0030] Add 46g of compound III, 3-oxo-4-ene-17-cyano, into the reaction flask, add 230g of glacial acetic acid, 92g of tert-butanol, stir well, slowly add 69g of sulfuric acid dropwise, and react at a temperature of 15°C for 12h, monitored by TLC until the reaction is complete. 82.2 g of sodium carbonate was added to terminate the reaction. Add 920ml of water for water...

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Abstract

The invention relates to a preparation method for finasteride intermediate. According to the method, a product compound I, namely N-tert-butyl-3-oxo-4-olefinic-17 beta-finasteride formamide intermediate, is prepared by carrying out two steps of cyaniding and amidation on a compound II, namely androstenedione. A reaction scheme is shown in the specification. 4-androstenedione is used as a raw material, the resource is richer, and the cost is lower; the synthesis time is short, and the obtained finasteride intermediate is high in purity yield, and the HPLC is greater than or equal to 98%; and the yield is greater than or equal to 110%.

Description

technical field [0001] The invention relates to a preparation method of a steroidal drug intermediate, in particular to a preparation method of a finasteride intermediate. Background technique [0002] Finasteride, a 4-azasteroid compound, is a specific inhibitor of the intracellular enzyme-type II 5α-reductase, which can inhibit benign prostatic hyperplasia and prevent hair loss. [0003] Domestic manufacturers generally use dienolone acetate as a raw material to synthesize compound Ⅰ through six steps of hydrogenation, hydrolysis, esterification, oxidation, hydrolysis and amidation; compound Ⅰ undergoes four steps of ring opening, ring closure, hydrogenation and dehydrogenation Synthesis of finasteride. Patent CN201210002148 uses the product obtained by compound I through ring-opening and cyclization as raw materials, and through bromination, eliminates the two-step synthesis of finasteride. The cost of raw materials is high, and the produced wastewater and quinones are p...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J41/00
Inventor 周建生郑承刚杨艳青郑建雄侯海波刘林代先华
Owner 湖北竹溪人福药业有限责任公司
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