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Synthetic method of 3-carbonyl-4-aza-5 alpha-androstane-17 beta-carboxylic acid methyl ester

A technology of methyl carboxylate and synthesis method, which is applied in the field of synthesis of 3-carbonyl-4-aza-5α-androst-17β-methyl carboxylate, which can solve the problem that isomers cannot be recycled and applied mechanically, which limits industrial production , Difficult purification and separation, etc., to achieve the effect of facilitating industrial implementation, avoiding reaction condition problems, and reducing production costs

Active Publication Date: 2011-11-16
HUNAN KEREY BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Using this method, 15-20% of beta isomers are mixed in the product as determined by HPLC. The properties of this isomer are close to the product, and it is not easy to purify and separate. It needs to be removed by multiple recrystallizations, resulting in a decrease in product yield. At the same time, a large number of precious metal catalysts Pd / C are used and the isomer cannot be recycled and used mechanically, which leads to an increase in product cost and limits its industrial production

Method used

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  • Synthetic method of 3-carbonyl-4-aza-5 alpha-androstane-17 beta-carboxylic acid methyl ester
  • Synthetic method of 3-carbonyl-4-aza-5 alpha-androstane-17 beta-carboxylic acid methyl ester
  • Synthetic method of 3-carbonyl-4-aza-5 alpha-androstane-17 beta-carboxylic acid methyl ester

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Effect test

Embodiment 1

[0022] Preparation of 3-carbonyl-4-aza-5α-androst-17β-carboxylate methyl ester:

[0023] Add 3-carbonyl-4-aza-5-androstene-17β-carboxylate methyl ester (33.14g; Fw: 331.45; 100 mmol), followed by the addition of 200 mL of ethanol and 3.31 g of Raney-Ni. Then 60 g of triethylamine formate were added. The system continued to stir for 2h under reflux. After the reaction was completed, after the system was cooled to room temperature, the solid was removed by filtration, and the filtrate was evaporated to dryness. After adding ice water, it was extracted with dichloromethane. The extract was washed and dried, and evaporated to dryness to obtain a crude product. The α-isomer in the crude product was analyzed by HPLC. : β isomer>99:1, the product was subsequently recrystallized from a solvent to obtain 31.67 g of the target product, yield: 95%, HPLC content greater than 99%.

Embodiment 2

[0025] Preparation of 3-carbonyl-4-aza-5α-androst-17β-carboxylate methyl ester

[0026] Add 3-carbonyl-4-aza-5-androstene-17β-carboxylate methyl ester (33.14g; Fw: 331.45; 100 mmol), followed by the addition of 200 mL of methanol and 3.31 g of Raney-Ni. Then 60 g of triethylamine formate were added. The system continued to stir for 5h under reflux. After the reaction was completed, after the system was cooled to room temperature, the solid was removed by filtration, and the filtrate was evaporated to dryness. After adding ice water, it was extracted with dichloromethane. The extract was washed and dried, and evaporated to dryness to obtain a crude product. The α-isomer in the crude product was analyzed by HPLC. : β isomer>98:2, in the product, the product was then recrystallized from a solvent to obtain 31.67 g of the target product, yield: 95%, and the HPLC content was greater than 99%.

Embodiment 3

[0028] Preparation of 3-carbonyl-4-aza-5α-androst-17β-carboxylate methyl ester

[0029] Add 3-carbonyl-4-aza-5-androstene-17β-carboxylate methyl ester (33.14g; Fw: 331.45; 100 mmol), followed by the addition of 200 mL of methanol and 0.33 g of Raney-Ni. Then 35 g of triethylamine formate were added. The system continued to stir for 24h under reflux. After the reaction was completed, after the system was cooled to room temperature, the solid was removed by filtration, and the filtrate was evaporated to dryness. After adding ice water, it was extracted with dichloromethane. The extract was washed and dried, and evaporated to dryness to obtain a crude product. The α-isomer in the crude product was analyzed by HPLC. : β isomer>97:3, in the product, the product was then recrystallized from a solvent to obtain 31.67 g of the target product, yield: 95%, and the HPLC content was greater than 99%.

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Abstract

The invention discloses a synthetic method of 3-carbonyl-4-aza-5 alpha-androstane-17 beta-carboxylic acid methyl ester. The method comprises the following steps that 3-carbonyl-4-aza-5-androstene-17 beta-carboxylic acid methyl ester is dissolved in a solvent to react with organic amine formate under catalysis of a metal catalyst; then an object product 3-carbonyl-4-aza-5 alpha-androstane-17 beta-carboxylic acid methyl ester is collected from reaction products. The method of the invention has mild reaction conditions and can realize complete reaction, and the product can have a purity higher than 99% after simple purification. All reagents used in the reaction are easily available. Besides, reaction yield is high; reaction conditions are mild; and the solvent can be recovered for utilization, so as to facilitate industrialized enforcement.

Description

technical field [0001] The invention relates to a synthesis method for preparing finasteride important intermediate 3-carbonyl-4-aza-5α-androst-17β-carboxylate methyl ester. Background technique [0002] Finasteride (finasteride, trade name Proscar, code name MK-906) is a drug for the treatment of benign prostatic hyperplasia developed by Merck & Co. of the United States, which was launched in 1992. Benign prostatic hyperplasia (BPH) is a common disease in older men and the most common cause of dysuria in men. Studies have found that elevated levels of dihydrotestosterone are the cause of BPH. 5α-reductase inhibitors can inhibit the conversion of testosterone into dihydrotestosterone to achieve the purpose of treating BPH. Make the proliferated prostate shrink without dihydrotestosterone, thus showing curative effect. The medicine has definite curative effect and few side effects. Its structural formula is as follows: [0003] [0004] At present, in the existing tec...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J73/00
Inventor 左前进羊向新吴来喜
Owner HUNAN KEREY BIOTECH
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