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Synthetic method for dibenzepin derivative

A technology of dibenzepines and a synthesis method, applied in the direction of organic chemistry and the like, can solve the problems of inconvenient handling of metal catalysts, environmental pollution and the like, and achieve the effects of simple operation and high yield

Active Publication Date: 2015-04-08
TIANJIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0026] The disadvantage is that the post-processing of the metal catalyst is inconvenient and pollutes the environment to a certain extent.

Method used

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  • Synthetic method for dibenzepin derivative
  • Synthetic method for dibenzepin derivative
  • Synthetic method for dibenzepin derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] A method for synthesizing diphenazepine derivatives (I), comprising the steps of:

[0048] (1) Preparation of 2-(N-methyl-N-phenyl)amino-N’-methoxybenzamide (VII-a)

[0049]Add o-bromobenzoic acid (II-a) (4.00 g), aniline (III-a) (2.79 g), nitrogenmethylmorpholine (3.3 mL), cuprous oxide (1.43 g) to dioxane ( 50 mL), heated to reflux for 4 hours under nitrogen protection. After the reaction was completed, cool to room temperature, remove the solid residue by suction filtration under reduced pressure, acidify the filtrate with 1M aqueous hydrochloric acid to pH=5, and obtain a white solid as 2-(N-phenyl)aminobenzoic acid (IV-a) by suction filtration.

[0050] Compound (IV-a) was dissolved in N,N-dimethylformamide (40 mL), sodium hydride (0.96 g) was added under ice cooling, and stirred at room temperature for half an hour. Transfer to an ice bath, add iodomethane (3.7 mL) dropwise, and stir at 0°C for one hour. After the reaction is over, slowly add water in an ice ba...

Embodiment 2

[0058] A method for synthesizing diphenazepine derivatives (I), comprising the steps of:

[0059] (1) Preparation of 2-[N-methyl-N-(4-methoxy)phenyl]amino-N’-methoxybenzamide (VII-b)

[0060] Add o-bromobenzoic acid (II-a) (4.00g), 4-methoxyaniline (III-b) (3.69g), nitrogenmethylmorpholine (3.3mL), cuprous oxide (1.43g) to Dioxane (50 mL) was heated to reflux for 4 hours under the protection of nitrogen. After the reaction was completed, cool to room temperature, remove the solid residue by suction filtration under reduced pressure, acidify the filtrate to pH=5 with 1M aqueous hydrochloric acid solution, and obtain a white solid of 2-[N-(4-methoxy)phenyl]aminobenzene by suction filtration Formic acid (IV-b).

[0061] Compound (IV-b) was dissolved in N,N-dimethylformamide (40 mL), sodium hydride (0.96 g) was added under ice cooling, and stirred at room temperature for half an hour. Transfer to an ice bath, add iodomethane (3.7 mL) dropwise, and stir at 0°C for one hour. Aft...

Embodiment 3

[0069] A method for synthesizing diphenazepine derivatives (I), comprising the steps of:

[0070] (1) Preparation of 2-[N-methyl-N-(3-methoxy)phenyl]amino-N’-methoxybenzamide (VII-c)

[0071] Add o-bromobenzoic acid (II-a) (4.00 g), 3-methoxyaniline (III-c) (3.69 g), nitrogen methylmorpholine (3.3 mL), cuprous oxide (1.43 g) to Dioxane (50 mL) was heated to reflux for 4 hours under the protection of nitrogen. After the reaction, cool to room temperature, remove the solid residue by suction filtration under reduced pressure, the filtrate is adjusted to pH=5 with 1M hydrochloric acid aqueous solution, and the white solid is 2-[N-(3-methoxy)phenyl]aminobenzene by suction filtration Formic acid (IV-c).

[0072] Compound (IV-c) was dissolved in N,N-dimethylformamide (40 mL), sodium hydride (0.96 g) was added under ice cooling, and stirred at room temperature for half an hour. Transfer to an ice bath, add iodomethane (3.7 mL) dropwise, and stir at 0°C for one hour. After the rea...

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Abstract

The invention discloses a synthetic method for a dibenzepin derivative. The method comprises the steps that substituted bromobenzoic acid, cuprous oxide and N-methylmorpholine are reacted with substituted aniline, so that 2-(N-substituted phenyl) aminobenzoic acid derivative (IV) is produced; the compound (IV) is reacted with sodium hydride and methyl iodide, so that 2-(N-methyl-N-substituted phenyl) aminobenzoic acid methyl ester derivative (V) is produced; the compound (V) is subjected to basic hydrolysis, so that 2-(N-methyl-N-substituted phenyl) aminobenzoic acid derivative (VI) is obtained; the compound (VI) is condensed with methoxy lamine hydrochloride under the effect of carbonyldiimidazole, so that 2-(N-methyl-N-substituted phenyl) amino-N'-methoxybenzamide derivative (VII) is produced; the compound (VII) is reacted with iodobenzene diacetate in acetonitrile at room temperature, so that the dibenzepin derivative (I) is obtained. The method has the advantages that the operation is simple, the reaction raw materials and reaction reagents are easy to obtain, the yield is higher and the like.

Description

technical field [0001] The invention relates to a method for synthesizing diphenazepine derivatives. Background technique [0002] The dibenzepine structure exists in a variety of pharmaceutical molecules or important intermediates in the synthesis of some natural products, such as the antidepressant drug Dibenzepin [1] (A), histone deacetylase inhibitors [2] (B), anti-inflammatory drugs [3] (C), the schizophrenia drug clozapine [4] (D), Gastrozepin, the first-generation M1-selective muscarinic receptor antagonist [5] (E) Dibenzoxazepinone, a drug that is physiologically active against type 1 immunodeficiency virus [6] (F) etc. Therefore, the pharmaceutical molecule or natural product containing this type of structure can be prepared from this type of dibenzazepine compound. [0003] [0004] The relevant literature is as follows: [0005] Attwood, D.; Gibson, J. J. Pharm. Pharmac. 1978, 30, 176-180. [0006] Binaschi, M.; Boldetti, A.; Gianni, M.; Maggi, C.A.; Ge...

Claims

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Application Information

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IPC IPC(8): C07D243/38
CPCC07D243/38
Inventor 杜云飞李旭明张翔赵康
Owner TIANJIN UNIV
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