Synthetic method of (2-methyl-5-nitro phenyl) guanidine sulfate

A technology of nitrophenyl and synthesis method, applied in chemical instruments and methods, preparation of organic compounds, organic chemistry and other directions, can solve the problems of low product purity, low yield, long reaction time, etc., and achieve high product purity, The effect of high yield and simple reaction conditions

Active Publication Date: 2014-04-02
YIYUAN XINQUAN CHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The disadvantage of this technology is: the cyanamide method often requires special conditions, the reaction time is long, and cyanamide is highly toxic, unstable, and easily condensed into dicyandiamide, resulting in low product purity and low yield

Method used

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  • Synthetic method of (2-methyl-5-nitro phenyl) guanidine sulfate

Examples

Experimental program
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Embodiment 1

[0019] Add 20g (0.131mol) of 2-amino-4 nitrotoluene into a three-necked flask, add 30ml of ethanol and 8ml of DMF, adjust the base to pH=12 with 10% NaOH, stir for 20min, add 33g (0.134mol) of oxymethylisourea Sulphate, heated to reflux, reacted for 5h; after the reaction, use 8%H 2 SO 4 Adjust the acid to pH = 6.5, and then keep it warm for 40 minutes; after the keep warm, cool down to 0°C, filter with suction, wash twice with 120ml ethanol, and dry to get 31.16g of solid product with a purity of 99.7% and a yield of 83.0%.

Embodiment 2

[0021] Add 20g (0.131mol) of 2-amino-4 nitrotoluene into a three-necked flask, add 35ml of ethanol and 6ml of DMF, adjust the base to pH=11 with 25% ammonia water, stir for 30min, add 32g (0.131mol) of oxymethylisourea Sulphate, heated to reflux, reacted for 6h; after the reaction, use 10%H 2 SO 4 Adjust the acid to pH=7.0, and then keep it warm for 30 minutes; after the keep warm, cool down to 0°C, filter with suction, wash twice with 100ml ethanol, and dry to get 31.85g of solid product with a purity of 99.8% and a yield of 81.2%.

Embodiment 3

[0023] Add 20g (0.131mol) of 2-amino-4 nitrotoluene into a three-necked flask, add 38ml of ethanol and 5ml of DMF, adjust the base to pH=13 with 25% ammonia water, stir for 30min, add 35g (0.144mol) of oxymethylisourea Sulphate, heated to reflux, reacted for 8h; after the reaction, use 10%H 2 SO 4 Adjust the acid to pH=6.0, and then keep it warm for 30 minutes; after the keep warm, cool down to 0°C, filter with suction, wash twice with 100ml ethanol, and dry to get 32.62g of solid product with a purity of 99.9% and a yield of 85.0%.

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Abstract

The invention belongs to the technical field of medicine intermediates and particularly relates to a synthetic method of an imatinib mesylate intermediate, namely (2-methyl-5-nitro phenyl) guanidine sulfate. The synthetic method comprises the following steps of by adopting 2-amino-4-nitrotoluene and oxy-methylisothiourea sulfate as a material, reacting in alcohol and DMF under the alkaline condition, then carrying out acid adjustment and suction filtration to obtain the (2-methyl-5-nitro phenyl) guanidine sulfate. The synthetic method has the advantages that the oxy-methylisothiourea sulfate is adopted for replacing cyanamide to carry out reaction, the material is easily available, the reaction condition is simple, no side products difficult to treat are generated, the purity of a product is high and is up to more than 99.7% and the yield is high.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical intermediates, in particular to a method for synthesizing imatinib mesylate intermediate (2-methyl-5-nitrophenyl)guanidine sulfate. Background technique [0002] (2-Methyl-5-nitrophenyl) guanidine sulfate is an important intermediate in the synthesis of imatinib mesylate. The chemical name of imatinib mesylate is 4-(4-methyl-1 -piperazine)methyl-N-4-methyl-3-4-(3-pyridine)-2-pyrimidineaminophenyl-aniline methanesulfonate, a protein kinase inhibitor, is the first Mode of Action (MOA) for Kinase Inhibition, Marketed Drugs Acting as Signal Sensing Inhibitors (STIs). [0003] The structural formula of (2-methyl-5-nitrophenyl)guanidine is as follows: [0004] [0005] In the prior art, the synthesis of (2-methyl-5-nitrophenyl) guanidine is to use 2-amino-4 nitrotoluene as a raw material, which reacts with cyanamide to generate, and the process route is as follows: [0006] [0007] The ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C279/18C07C277/08
Inventor 唐锋张立明
Owner YIYUAN XINQUAN CHEM
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