Synthesis method of 3 beta-acetoxy-17-aryl androsta-5,16-diene

A technology of acetoxyandrostane and acetoxyl, applied in the field of synthesis of 3β-acetoxy-17-arylandrost-5,16-diene, can solve the problems of unfavorable pharmaceutical production industrial implementation, expensive metal catalysts, initial Rare raw materials, etc.

Inactive Publication Date: 2018-01-26
TAIZHOU POLYTECHNIC COLLEGE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] However, although many of the above-mentioned synthetic schemes are very effective, there are still some disadvantages, such as rare starting materials, expensive metal catalysts and a large amount of waste generation, etc., which are not conducive to the implementation of the pharmaceutical production industry.

Method used

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  • Synthesis method of 3 beta-acetoxy-17-aryl androsta-5,16-diene
  • Synthesis method of 3 beta-acetoxy-17-aryl androsta-5,16-diene
  • Synthesis method of 3 beta-acetoxy-17-aryl androsta-5,16-diene

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preparation example Construction

[0016] A method for synthesizing 3β-acetyloxy-17-arylandrosta-5,16-diene of the present invention comprises the following steps: using 17-trifluoromethanesulfonyloxy-3β-acetyloxyandrost-5, 16-diene as raw material, toluene as solvent, in nickel catalyst Ni(PCy 3 ) 2 Cl 2 Under the influence of reaction, 3β-acetoxy-17-aryl androst-5,16-diene compound was obtained after reaction for 6h:

[0017]

[0018] The 3β-acetoxy-17-arylandrost-5,16-diene compound of the present invention includes the following structural formula:

[0019]

[0020] Reagent and condition of the present invention: compound (0.924g, 2.0mmol), Ni(PCy 3 ) 2 Cl 2 (0.07g, 0.1mmol), K 3 PO 4 (1.30g, 6.0mmol), arylboronic acid (3.0mmol), toluene (15mL), 100°C, 6h; yield: 52-85%.

[0021] test instrument

[0022] Infrared spectrum analysis: Bruker tensor 27 infrared spectrometer, KBr tablet method, detection range is 4000~400cm -1 ; Melting point measurement: WRR melting point instrument (Shanghai Pr...

Embodiment 1

[0023] Example 1: Synthesis of 3β-acetoxy-17-phenylandrost-5,16-diene (3a)

[0024]

[0025] Weigh 0.924g (2.0mmol) of 17-trifluoromethanesulfonyloxy-3β-acetoxy-androst-5,16-diene (1), catalyst Ni (PCy 3 ) 2 Cl 2 0.07g (0.1mmol), K 3 PO 4 1.30g (6.0mmol) and 0.366g (3.0mmol) of phenylboronic acid were added to 15mL of toluene, and stirred at room temperature for 5min. Then, under the protection of nitrogen, the reaction was stirred at 100° C. for 6 h, and the reaction progress was tracked by TLC (EtOAc / hexanes 1:8). After the reaction was completed, the toluene solvent was evaporated under vacuum, and the residue was passed through CH 2 Cl 2 Extract 2 times, 10 mL each time, combine the organic phases, wash the organic phases with water and saturated brine twice, 5 mL each time, anhydrous Na 2 SO 4 dry. Evaporate CH 2 Cl 2 Solvent, the crude product was purified by flash chromatography (silica gel, EtOAc / hexanes, 1 / 40) to obtain a white solid product, yield: 85%...

Embodiment 2

[0026] Example 2: Synthesis of 3β-acetoxy-17-(3-fluorophenyl)androst-5,16-diene (3b)

[0027]

[0028] Weigh 0.924g (2.0mmol) of 17-trifluoromethanesulfonyloxy-3β-acetoxy-androst-5,16-diene (1), catalyst Ni (PCy 3 ) 2 Cl 2 0.07g (0.1mmol), K 3 PO 4 1.30 g (6.0 mmol) and 0.42 g (3.0 mmol) of 3-fluorophenylboronic acid were added to 15 mL of toluene, and stirred at room temperature for 5 min. Then, under the protection of nitrogen, the reaction was stirred at 100° C. for 6 h, and the reaction progress was tracked by TLC (EtOAc / hexanes 1:8). After the reaction was completed, the toluene solvent was evaporated under vacuum, and the residue was passed through CH 2 Cl 2 Extract 2 times, 10 mL each time, combine the organic phases, wash the organic phases with water and saturated brine twice, 5 mL each time, anhydrous Na 2 SO 4 dry. Evaporate CH 2 Cl 2 Solvent, the crude product was purified by flash chromatography (silica gel, EtOAc / hexanes, 1 / 40) to obtain a light ye...

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Abstract

The invention relates to a synthesis method of 3 beta-acetoxy-17-aryl androsta-5,16-diene. The method comprises steps as follows: 17-trifluoromethanesulfonyloxy-3 beta-acetoxy androsta-5,16-diene as araw material and toluene as a solvent react under the action of a nickel catalyst Ni(PCy3)2Cl2 for 6 h, and a 3 beta-acetoxy-17-aryl androsta-5,16-diene compound in the description is obtained. The 3beta-acetoxy-17-aryl androsta-5,16-diene compound has the structural formula shown in the description.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, and specifically relates to a synthesis method of 3β-acetoxy-17-arylandrost-5,16-diene. Background technique [0002] The transformation and modification of natural steroids have attracted more and more attention. After some specific modifications, such as the modification of steroidal rings and side chains, some important derivatives of steroidal compounds with better biological activity than the parent can be obtained [Levina , I.S.; Pokrovskaya, E.V.; ​​Kulikova, L.E.; Kamernitzky, A.V.; Kachala, V.V.; Such as abiraterone acetate (abirateroneacetate, which has been used in clinical figure 1 ), chemically named 17-(3-pyridyl)androst-5,16-diene-3β-acetate, is an orally effective irreversible inhibitor of CYP 17 enzymes developed by Centocor Ortho, through conversion into Bitterone inhibits the androgen produced by the testes and other parts of the body such as the adrenal gland. On April 28,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J13/00
Inventor 王立中卞小琴刘竺云王存德栗扬王婷代晨路
Owner TAIZHOU POLYTECHNIC COLLEGE
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