Synthetic method of exemestane

A synthetic method, the technology of exemestane, applied in the field of pharmaceutical chemical synthesis, can solve the problems of difficult purification of oxidation products, large amount of oxidizing agent, expensive starting materials, etc., and achieve the effect of easy purification, high yield and improved yield

Active Publication Date: 2021-02-26
SHAANXI SCI TECH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The amount of oxidant used in the dehydrogenation reaction of the existing method is large, the purification of the oxidation product

Method used

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  • Synthetic method of exemestane

Examples

Experimental program
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Embodiment 1

[0042] Allyl diethyl phosphate (52.4g, 0.27mol) was dissolved in anhydrous N,N-dimethylformamide (DMF, 200mL), and then 10% palladium carbon (2.5g) was added. Stirred and reacted for 0.5h, then added anhydrous sodium carbonate (38.2g, 0.36mol) and 6-methyleneandrost-4-ene-3,17-dione (26.9g, 90mmol), heated to reflux for 16h . After cooling to room temperature, the solid insoluble matter was removed by suction filtration, and most of the DMF was evaporated from the filtrate under reduced pressure at 80°C, then water (100 mL) was added, and extracted with dichloromethane (70 mL×3). After the organic phases were combined, they were washed with saturated sodium chloride solution (100mL×2), and the layers were separated. The organic phase was evaporated under reduced pressure at 30°C to remove the solvent, and the residue was dissolved in methanol (80mL), decolorized with activated carbon (1g), and filtered. Crystallize at room temperature, recrystallize with ethanol (50mL), and d...

Embodiment 2

[0045] Allyl diethyl phosphate (52.4g, 0.27mol) was dissolved in anhydrous N,N-dimethylformamide (DMF, 300mL), and then 10% palladium carbon (1.9g) was added. Stirred and reacted for 0.5h, then added anhydrous potassium carbonate (49.8g, 0.36mol) and 6-methyleneandrost-4-ene-3,17-dione (26.9g, 90mmol), heated to reflux for 24h . After cooling to room temperature, the solid insoluble matter was removed by suction filtration, and most of the DMF was evaporated from the filtrate under reduced pressure at 80°C, then water (100 mL) was added, and extracted with dichloromethane (70 mL×3). After the organic phases were combined, they were washed with saturated sodium chloride solution (100mL×2), and the layers were separated. The organic phase was evaporated under reduced pressure at 30°C to remove the solvent, and the residue was dissolved in methanol (80mL), decolorized with activated carbon (1g), and filtered. Crystallize at room temperature, recrystallize with ethanol (50 mL), a...

Embodiment 3

[0047] Allyl diethyl phosphate (52.4g, 0.27mol) was dissolved in anhydrous N,N-dimethylformamide (DMF, 200mL), and then 10% palladium carbon (2.5g) was added. Stirred and reacted for 0.5h, then added anhydrous potassium carbonate (74.7g, 0.54mol) and 6-methyleneandrost-4-ene-3,17-dione (26.9g, 90mmol), heated to reflux for 24h . After cooling to room temperature, the solid insoluble matter was removed by suction filtration, and most of the DMF was evaporated from the filtrate under reduced pressure at 80°C, then water (100 mL) was added, and extracted with dichloromethane (70 mL×3). After the organic phases were combined, they were washed with saturated sodium chloride solution (100mL×2), and the layers were separated. The organic phase was evaporated under reduced pressure at 30°C to remove the solvent, and the residue was dissolved in methanol (80mL), decolorized with activated carbon (1g), and filtered. Crystallize at room temperature, recrystallize with ethanol (50 mL), a...

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Abstract

The invention discloses a synthetic method of exemestane. The method comprises the following steps: by taking 6-methyleneandrost-4-ene-3,17-dione as a raw material, directly carrying out selective [delta]1,2 dehydrogenation reaction on the raw material in an organic solvent under the protection of nitrogen, in the presence of an inorganic base and in the presence of an organic phosphorus ester compound as a ligand under the condition of heating reflux under the catalysis of a catalyst, and after the reaction is carried out for a period of time, and carrying out post-treatment to obtain the exemestane. Compared with a traditional synthesis method, the route has the advantages that 1,2 selective dehydrogenation is carried out on 6-methyleneandrost-4-ene-3,17-dione through the catalyst to prepare the exemestane, the use of benzoquinone oxidants, Jones oxidants and the like is avoided, the subsequent purification process is simplified, the yield is increased, and the pollution problem in the production process is reduced.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical chemical synthesis, and in particular relates to a synthesis method of exemestane. Background technique [0002] The chemical name of Exemestane is 1,4-diene-3,17-dione-6-methyleneandrostane or 6-methyleneandrostane-1,4-diene-3,17 -Diketone, white or off-white crystalline powder, melting point 192-193°C, odorless, easily soluble in chloroform, slightly soluble in ethyl acetate, acetone, methanol or ethanol, almost insoluble in water. In 1992, Di Salle found that the structure of exemestane was similar to the natural substrate of steroidal aromatase, and it could irreversibly bind to the active site of aromatase to inactivate it. Exemestane can specifically inactivate aromatase and block the aromatization reaction, thereby inhibiting the production of estrogen and reducing the level of estrogen in the blood to achieve the purpose of treating breast cancer. Exemestane is an oral irreversibl...

Claims

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Application Information

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IPC IPC(8): C07J1/00
CPCC07J1/0011Y02P20/55
Inventor 陈旺胡代花冯自立赵正栋
Owner SHAANXI SCI TECH UNIV
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