Preparation method of 1-(6-chloropyridazine-4-yl)ethyl-1-one

A technology of chloropyridazine and ethyl, applied in the field of preparation of pharmaceutical intermediates, can solve problems such as unreported synthesis methods, and achieve the effects of simple post-processing, good stability and high yield

Pending Publication Date: 2022-02-11
CHEMSHUTTLE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] 1-(6-chloropyridazin-4-yl) ethyl-1-one is exactly a kind of this kind of compound newly designed in literature report, and its synthetic method has not been reported

Method used

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  • Preparation method of 1-(6-chloropyridazine-4-yl)ethyl-1-one
  • Preparation method of 1-(6-chloropyridazine-4-yl)ethyl-1-one
  • Preparation method of 1-(6-chloropyridazine-4-yl)ethyl-1-one

Examples

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Embodiment 1

[0027] A preparation method of 1-(6-chloropyridazin-4-yl)ethyl-1-one, comprising the steps:

[0028] (1) DMF (50 mL, 0.65 mol) was added to a 100 mL single-necked flask, compound 1 (5-chloropyridazin-3-ol, 10.0 g, 76.92 mmol, 1 eq) was added under stirring, and the solution was clarified after stirring for 5 minutes. Tributyl (1-ethoxyethylene) tin (27.8g, 76.92mmol, 1eq), triethylamine (15.5g, 153.84mmol, 2eq) were successively added to it, and bistriphenylphosphonium disulfide was added under nitrogen protection Palladium chloride (2.7g, 3.85mmol, 0.05eq), then continued to react at 90°C for 3h under nitrogen protection, cooled to room temperature, added water to quench the reaction, and then extracted with ethyl acetate 3 times, the organic phases were combined, Dry over anhydrous sodium sulfate, filter, and concentrate to obtain the crude product. The crude product is purified by silica gel column chromatography and eluted with dichloromethane:methanol=20:1 volume ratio is...

Embodiment 2

[0036] A preparation method of 1-(6-chloropyridazin-4-yl)ethyl-1-one, comprising the steps:

[0037] (1) DMF (50 mL, 0.65 mol) was added to a 100 mL single-necked flask, compound 1 (5-chloropyridazin-3-ol, 10.0 g, 76.92 mmol, 1 eq) was added under stirring, and the solution was clarified after stirring for 5 minutes. Tributyl(1-ethoxyethylene)tin (41.76g, 115.38mmol, 1.5eq), DIEA (29.7g, 230.76mmol, 3eq) were successively added thereto, and bistriphenylphosphorus dichloride was added under nitrogen protection. Palladium (5.4 g, 7.70 mmol, 0.1 eq), then continued to react at 120 ° C for 1 h under nitrogen protection, cooled to room temperature, added water to quench the reaction, and then extracted with ethyl acetate 3 times, the organic phases were combined, no Dry over sodium sulfate, filter, and concentrate to obtain the crude product. The crude product is purified by silica gel column chromatography and eluted with dichloromethane:methanol=20:1 volume ratio isocratic to obt...

Embodiment 3

[0046] A preparation method of 1-(6-chloropyridazin-4-yl)ethyl-1-one, comprising the steps:

[0047] (1) DMF (50 mL, 0.65 mol) was added to a 100 mL single-necked flask, the raw material compound 1 (5-chloropyridazin-3-ol 10.0 g, 76.92 mmol, 1 eq) was added under stirring, and the solution was clarified after stirring for 5 minutes. Tributyl (1-ethoxyethylene) tin (27.8g, 76.92mmol, 1eq), triethylamine (38.7g, 384.60mmol, 5eq) were successively added to it, and bistriphenylphosphonium disulfide was added under nitrogen protection Palladium chloride (10.8 g, 15.4 mmol, 0.2 eq), then continued to react at 140 ° C for 1 h under nitrogen protection, cooled to room temperature, added water to quench the reaction, and then extracted with ethyl acetate 3 times, the organic phases were combined, Dry over anhydrous sodium sulfate, filter, and concentrate to obtain the crude product. The crude product is purified by silica gel column chromatography and eluted with dichloromethane:methan...

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Abstract

The invention discloses a preparation method of 1-(6-chloropyridazine-4-yl)ethyl-1-one. The preparation method comprises the following specific steps: (1) taking a compound 1 as a starting raw material, and carrying out stillale coupling reaction to prepare a compound 2; (2) carrying out hydrolysis reaction on the compound 2 to prepare a compound 3; and (3) reacting the compound 3 with phosphorus oxychloride to prepare a target product, namely 1-(6-chloropyridazine-4-yl)ethyl-1-one. The preparation method is short in process route, convenient to operate, mild in reaction condition, easy to control, low in cost, suitable for process amplification, easy in product purification and high in yield.

Description

technical field [0001] The invention relates to a preparation method of a pharmaceutical intermediate, in particular to a preparation method of 1-(6-chloropyridazin-4-yl)ethyl-1-one. Background technique [0002] Pyridazine molecular building blocks are an important class of organic heterocyclic pharmaceutical intermediates. Studies have found that a variety of pyridazine derivatives have good biological activities, such as: anti-tumor, insecticidal, bactericidal, herbicidal, plant biological regulation, etc. . It is more important to design and synthesize more novel pyridazine molecular building blocks, so as to react with the parent of active molecules, and then develop small molecule drugs with better activity. [0003] 1-(6-Chloropyridazin-4-yl)ethyl-1-one is a kind of compound of this type newly designed by literature reports, and its synthesis method has not been reported. SUMMARY OF THE INVENTION [0004] In view of the above problems, the present invention provid...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D237/14
CPCC07D237/14
Inventor 邵加春
Owner CHEMSHUTTLE
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