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Preparation method of 4-[(5-bromo-4,6-dichloro-2-pyrimidinyl)amino] cyanobenzene

A technology of benzonitrile and amino, which is applied in the field of compound preparation, can solve the problems of unsuitability for industrial production, high impurity content of products, and low product yield, and achieve complete and stable reaction, good product quality and low impurity content Effect

Active Publication Date: 2011-03-30
ZHEJIANG JIUZHOU PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

According to the given reagents, the following problems were found: the use of liquid bromine, which is highly irritating and inconvenient to operate, was used as the bromination reagent, which was not suitable for industrial production; the use of methanol as the reaction solvent made the raw materials insoluble in the reaction system, resulting in a reaction Incomplete serious problems, resulting in low product yield; high impurity content in the product, poor product quality

Method used

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  • Preparation method of 4-[(5-bromo-4,6-dichloro-2-pyrimidinyl)amino] cyanobenzene
  • Preparation method of 4-[(5-bromo-4,6-dichloro-2-pyrimidinyl)amino] cyanobenzene
  • Preparation method of 4-[(5-bromo-4,6-dichloro-2-pyrimidinyl)amino] cyanobenzene

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Add 8 grams of raw materials 4-[(4,6-dichloro-2-pyrimidinyl)amino]benzonitrile and 65 ml of dichloromethane into the reaction flask, heat to dissolve and cool to room temperature 25-30°C, add NBS dropwise (n-Bromosuccinimide) / dichloromethane solution 10.8g / 120 ml, continue to react for 18 hours, GC detects that the basic reaction is complete, post-treatment, add 5% aqueous sodium bicarbonate solution, separate layers, and concentrate the organic layer , 9.9 g of solid was obtained, the yield was 95%, and the GC purity was 95.6%. Melting point: 262.1°C-264.1°C. 1H NMR (500MHz, DMSO): 10.85 (s, 1H), 8.85 (s, 4H,); 13C NMR (500MHz, D2O): δ160.5, 155.9, 143.0, 133.2, 119.1, 106.6, 104.3.

Embodiment 2

[0030] Add 8 grams of raw materials 4-[(4,6-dichloro-2-pyrimidinyl)amino]benzonitrile and 65 ml of THF (tetrahydrofuran) into the reaction flask, heat to 45-50°C, add dibromohydantoin dropwise / THF solution 10.1g / 25ml, react at 40-45°C for 20 hours, GC detects that the basic reaction is complete, post-processing, distill about 40ml of THF under reduced pressure, add 80ml of 5% sodium hydroxide aqueous solution, stir for half an hour, filter, Washed with water and dried to obtain 9.7 g of solid with a yield of 93% and a GC purity of 95.4%. The structural data are the same as in Example 1.

Embodiment 3

[0032] Add 8 grams of raw materials 4-[(4,6-dichloro-2-pyrimidinyl)amino]benzonitrile and 65 ml of acetone into the reaction flask, add 10.5 g of dibromohydantoin / acetone solution dropwise at 30-35°C / 25 ml, after reacting at 30-35°C for 20 hours, the basic reaction was detected by GC, after treatment, about 40 ml of acetone was distilled under reduced pressure, 80 ml of 5% potassium carbonate aqueous solution was added and stirred for half an hour, filtered, washed with water, and dried to obtain 9.0 g solid, 90% yield, 95.2% GC purity. The structural data are the same as in Example 1.

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Abstract

The invention relates to a preparation method of 4-[(5-bromo-4,6-dichloro-2-pyrimidinyl)amino] cyanobenzene, which comprises the following steps: using 4-[(4,6-dichloro-2-pyrimidinyl)amino] cyanobenzene and a brominating agent as raw materials, and using an organic solvent as a reaction solvent to obtain the 4-[(5-bromo-4,6-dichloro-2-pyrimidinyl)amino] cyanobenzene, wherein the organic solvent can be an ester, ether, ketone, aromatic or aliphatic organic solvent, preferably tetrahydrofuran, ethyl acetate, dichloromethane or acetone. Based on the prior art, the method makes an improvement andhas the advantages of complete reaction, high reaction yield, low cost, low impurity content, high product quality and the like.

Description

technical field [0001] The present invention relates to a preparation method of a compound, in particular to a preparation method of 4-[(5-bromo-4,6-dichloro-2-pyrimidinyl)amino]benzonitrile. Background technique [0002] 4-[(5-bromo-4,6-dichloro-2-pyrimidinyl)amino]benzonitrile (English name: [0003] 4-[(5-bromo-4, 6-dichloro-2-pyrimidinyl)amino]-Benzonitrole), the chemical structure is as shown in formula I: [0004] [0005] CAS number: 269055-75-6, molecular formula is C 11 h 5 BrCl 2 N 4 . It is an important intermediate used to prepare some pyrimidine compounds (as shown in the following scheme 1) and anti-HIV-1 drugs (as shown in the following scheme 2), and has very high practical value in the fields of chemical synthesis and pharmaceuticals. [0006] [0007] At present, regarding the preparation method of Compound I, the route that has been reported is shown in the figure below (references: Bioorganic & Medicinal Chemistry Letters 11 (2001) 2235-2239 (...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D239/42
Inventor 车大庆张达
Owner ZHEJIANG JIUZHOU PHARM CO LTD
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