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The preparation method of 3-benzimidazolene derivative

A technology of benzimidazole and cyanomethylbenzimidazole, which is applied in the field of preparation of 3-benzimidazole chromene derivatives, can solve the problems of large amount of alkali, long reaction time, and low yield, and achieve convenient post-processing , low production cost and high yield

Active Publication Date: 2021-06-25
HUAIYIN TEACHERS COLLEGE
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] This method needs to prepare chroman-3-carbonitrile derivatives in advance, the consumption of alkali is larger, the reaction time is longer and the productive rate is on the low side

Method used

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  • The preparation method of 3-benzimidazolene derivative
  • The preparation method of 3-benzimidazolene derivative
  • The preparation method of 3-benzimidazolene derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Embodiment 1: the preparation method of 3-benzimidazole chromene derivative

[0029] Step 1) In a 25mL round bottom flask, add 2-cyanomethylbenzimidazole (1.0mmol), 2,3-dichlorobenzaldehyde (1.0mmol), 5,5-dimethyl-1,3-cyclo Hexandione (1.0 mmol), pyridine (0.1 mmol) and 2 mL of absolute ethanol were heated under reflux for 2 hours; during heating, the solvent was boiled.

[0030] Step 2) After the reaction is completed, cool to room temperature, a large amount of product precipitates out, suction filter, and wash the crude product with ethanol to obtain the pure product 2-amino-3-(1H-benzo[d]imidazole)-4-(2,3- Dichlorophenyl)-7,7-dimethyl-7,8-dihydro-4H-chromen-5(6H)-one, the structural formula is as follows:

[0031]

[0032] Yield: 79%; Pale yellow solid; H NMR spectrum (DMSO-d 6 , 400MHz) (δ, ppm): 11.48(s, 1H), 7.84(d, J=8.4Hz, 1H), 7.80(s, 2H), 7.40-7.24(m, 4H), 7.06-7.00(m, 2H), 5.32(s, 1H), 2.62(d, J=17.6Hz, 1H), 2.47(d, J=18.0Hz, 1H), 2.32(d, J=16.0Hz, 1H)...

Embodiment 2

[0033] Embodiment 2: the preparation method of 3-benzimidazole chromene derivative

[0034] Step 1) Add 2-cyanomethylbenzimidazole (1.0mmol), 3-nitrobenzaldehyde (1.0mmol), 5,5-dimethyl-1,3-cyclohexanedione into a 25mL round bottom flask (1.0mmol), pyridine (0.1mmol) and absolute ethanol 2mL, react under reflux conditions for 1 hour;

[0035] Step 2) After the reaction is completed, cool to room temperature, a large amount of product precipitates, filter with suction, and wash the crude product with ethanol to obtain the pure product 2-amino-3-(1H-benzo[d]imidazole)-7,7-dimethyl -4-(3-nitrophenyl)-7,8-dihydro-4H-chromen-5(6H)-one, the structural formula is as follows:

[0036]

[0037] Yield: 85%; yellow solid; H NMR spectrum (DMSO-d 6 , 400MHz) (δ, ppm): 11.29(s, 1H), 8.36(s, 1H), 8.00-7.95(m, 3H), 7.83(d, J=7.6Hz, 1H), 7.53(t, J= 8.0Hz, 1H), 7.42(d, J=7.2Hz, 1H), 7.30(d, J=7.2Hz, 1H), 7.05-7.00(m, 2H), 5.19(s, 1H), 2.62(d, J=17.6Hz, 1H), 2.51(d, J=16.4Hz, 1H), 2.35(d,...

Embodiment 3

[0038] Embodiment 3: the preparation method of 3-benzimidazole chromene derivative

[0039] Step 1) In a 25mL round bottom flask, add 2-cyanomethylbenzimidazole (0.8mmol), 4-methoxybenzaldehyde (0.8mmol), 5,5-dimethyl-1,3-cyclohexanedi Ketone (0.8mmol), pyridine (0.08mmol) and absolute ethanol 2mL were reacted under reflux for 3 hours;

[0040] Step 2) After the reaction is finished, cool to room temperature, a large amount of product precipitates out, filter with suction, and wash the crude product with ethanol to obtain the pure product 2-amino-3-(1H-benzo[d]imidazole)-4-(4-methoxy phenyl)-7,7-dimethyl-7,8-dihydro-4H-chromen-5(6H)-one, the structural formula is as follows:

[0041]

[0042] Yield: 56%; Pale yellow solid; H NMR spectrum (DMSO-d 6, 400MHz) (δ, ppm): 11.76(s, 1H), 7.80(s, 2H), 7.41(d, J=7.2Hz, 1H), 7.33-7.31(m, 3H), 7.05-7.00(m, 2H), 6.75(d, J=8.4Hz, 2H), 4.93(s, 1H), 3.63(s, 3H), 2.58(d, J=17.6Hz, 1H), 2.46(d, J=17.6Hz, 1H), 2.32(d, J=16.0Hz, 1H), 2.10(...

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Abstract

A kind of preparation method of 3-benzimidazolene derivative, put aromatic aldehyde, 2-cyanomethylbenzimidazole, 5,5-dimethyl-1,3-cyclohexanedione, pyridine and solvent into In a reactor, react under reflux conditions; after the reaction, the reaction system is cooled to room temperature to precipitate the product, and the crude product is obtained by suction filtration; the crude product is washed to obtain the pure product of 3-benzimidazole chromene derivative. After the reaction of the present invention is finished, the pure product can be obtained only by suction filtration and washing, the operation is simple, the aftertreatment is convenient, and the production cost is low.

Description

technical field [0001] The invention relates to a preparation method of 3-benzimidazole chromene derivatives, belonging to the technical field of organic compound synthesis. Background technique [0002] 3-Benzimidazolene compounds are a class of excellent Rho kinase inhibitors (Bioorganic & Medicinal Chemistry Letters, 2008, 18, 6390; Bioorganic & Medicinal Chemistry Letters, 2010, 20, 1939). The development of simple and efficient methods to synthesize such compounds is of great significance to the development and research of new drugs. [0003] At present, the preparation method of 3-benzimidazole chromene derivatives reported in the literature mainly contains the following two kinds: [0004] 1) Using o-phenylenediamine and chroman-3-carboxylic acid as raw materials, first in 2-(7-benzotriazole oxide)-N,N,N',N'-tetramethylurea Condensation of hexafluorophosphate and N,N'-diisopropylethylamine gives amide intermediate. Subsequent cyclization under the action of acetic ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D405/04
CPCC07D405/04
Inventor 王翔张载超支三军陈平胡华友韦长梅谢佳敏仝娜
Owner HUAIYIN TEACHERS COLLEGE