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Method for preparing 2-chloro-4-(1H-pyrazol-3-yl) benzonitrile by one-step method

A technology of benzonitrile and pyrazole, which is applied in the field of one-step preparation of 2-chloro-4-benzonitrile, can solve the problems of difficulty in chlorination reaction and many solvents, and achieve fast reaction speed, simple method and reduced production cycle effect

Pending Publication Date: 2021-10-22
江西金丰药业有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Although this method has a series of advantages such as allowing a variety of active functional groups to exist, and can react stereoselectively, the reaction requires multi-step reactions to complete, uses many solvents, and requires multiple distillations, extractions, drying and other processes. Chlorides and some heterocyclic boronic acids are difficult to carry out

Method used

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  • Method for preparing 2-chloro-4-(1H-pyrazol-3-yl) benzonitrile by one-step method
  • Method for preparing 2-chloro-4-(1H-pyrazol-3-yl) benzonitrile by one-step method

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Effect test

Embodiment 1

[0030] At room temperature, add compound I (2kg), compound II (3.3kg) and ethanol (5L) into the reaction kettle and stir to dissolve, then add potassium carbonate (3.2kg), vacuumize nitrogen replacement 4 times under stirring, nitrogen Add bis(triphenylphosphine)palladium dichloride (25.4g) under protection, then raise the temperature to 75°C to reflux, stir the reaction overnight (16h), and cool down to room temperature after the reaction is completed, remove the insoluble matter by filtration to obtain compound III in ethanol solution, under the protection of nitrogen, add concentrated hydrochloric acid (1.5kg) to the ethanol solution of the obtained compound III, stir and react overnight at room temperature, add 10% sodium hydroxide solution (5kg) after the reaction to adjust the pH to 6-7, and continue stirring Centrifuged after 30min, rinsed with 50% ethanol-water (1.25L) to obtain the crude wet product of compound IV; the crude wet product was added to ethanol (6.5L) and ...

Embodiment 2

[0032] At room temperature, add compound I (2kg), compound II (3.3kg) and ethanol (5L) into the reaction kettle and stir to dissolve, then add potassium carbonate (3.4kg), vacuumize nitrogen replacement 3 times under stirring, nitrogen Added bis(triphenylphosphine)palladium dichloride (25.4g) under protection, then raised the temperature to 80°C to reflux, stirred and reacted overnight (14h), cooled down to room temperature after the reaction was completed, filtered to remove insoluble matter, and obtained the ethanol solution of compound III , under the protection of nitrogen, add concentrated hydrochloric acid (1.8kg) to the ethanol solution of the obtained compound III, stir and react overnight at room temperature, add 10% sodium hydroxide solution (5.9kg) after the reaction to adjust the pH to 6-7, continue stirring Centrifuged after 30min, rinsed with 50% ethanol-water (1.25L) to obtain the crude wet product of compound IV; the crude wet product was added to ethanol (6.5L)...

Embodiment 3

[0034] At room temperature, add compound I (2kg), compound II (3.3kg) and ethanol (5L) into the reaction kettle and stir to dissolve, then add potassium carbonate (3.2kg), vacuumize nitrogen replacement twice under stirring, nitrogen Add bis(triphenylphosphine)palladium dichloride (25.4g) under protection, then raise the temperature to reflux at 85°C, stir the reaction overnight (12h), cool down to room temperature after the reaction is completed, remove the insoluble matter by filtration, and obtain the ethanol solution of compound III , under the protection of nitrogen, add concentrated hydrochloric acid (2.1kg) to the ethanol solution of the obtained compound III, stir and react overnight at room temperature, add 10% sodium hydroxide solution (7.0kg) after the reaction to adjust the pH to 6-7, and continue stirring Centrifuge after 30min, rinse with 50% ethanol-water (1.25L) to obtain the crude wet product of Compound IV; add the obtained crude wet product to ethanol (6.5L) ...

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Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a method for preparing 2-chloro-4-(1H-pyrazol-3-yl) cyanobenzene by a one-step method. The method comprises the following steps: adding a compound I, a compound II and ethanol into a reaction kettle, performing stirring, dissolving and clarifying, adding potassium carbonate, performing vacuumizing while stirring, performing nitrogen replacement, adding bis (triphenylphosphine) palladium dichloride under the protection of nitrogen, performing heating to reflux, performing stirring to react overnight, performing cooling to room temperature, and performing filtering to obtain an ethanol solution containing a compound III; and adding concentrated hydrochloric acid into the ethanol solution of the compound III, performing stirring reaction at room temperature overnight, adjusting the pH value to 6-7, continuing stirring and centrifuging, and performing leaching with ethanol-water to obtain a crude wet product of a compound IV. The preparation method adopts a one-step method for preparation, an intermediate does not need to be purified, links of distillation, extraction, layering, drying, redistillation and the like in an intermediate treatment process are omitted, and the method is simple, high in efficiency, energy-saving and environmentally friendly.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and more specifically relates to a method for preparing 2-chloro-4-(1H-pyrazol-3-yl)benzonitrile in one step. Background technique [0002] 2-Chloro-4-(1H-pyrazol-3-yl)benzonitrile is an important intermediate in the synthesis of formamide-structured androgen receptor (AR) antagonists, which can be used in the treatment of cancer, especially prostate cancer and other diseases requiring AR antagonism. In vitro experiments have confirmed that AR antagonists can inhibit the proliferation of prostate cells and promote their apoptosis; after treatment with AR antagonists in patients with early prostate cancer, the level of prostate specific antigen decreases, and the overall performance is a decrease in prostate volume and different symptoms. Degree of relief, prolonged survival time of patients. Therefore, as an intermediate of AR antagonists, the synthesis of 2-chloro-4-(1H-pyrazol-3-yl)...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D231/12
CPCC07D231/12
Inventor 聂丰彬占付灵柯维贤江小亮黄强
Owner 江西金丰药业有限公司
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