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Preparation method of carbamyl amino pyrazol derived compound

A carbamoylaminopyrazole and compound technology, which is applied in the field of preparation of carbamoylaminopyrazole derivative compounds, can solve the problems of high price and low total yield, reduce material loss, improve yield and purity , The effect of simplifying the process operation

Inactive Publication Date: 2019-02-22
浙江东邦药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0017] But the total yield of this route is on the low side, also used more expensive material PhI(OAc) 2 ,expensive

Method used

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  • Preparation method of carbamyl amino pyrazol derived compound
  • Preparation method of carbamyl amino pyrazol derived compound
  • Preparation method of carbamyl amino pyrazol derived compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Dissolve 2 g of the starting material 1-methyl-5-amino-4-ethoxycarbonylpyrazole in 24 mL of acetone at room temperature, and stir to dissolve. Then add 4.9g of triphenylchloromethane, stir and dissolve, then add 1.2g of pyridine dropwise, after the dropwise addition, heat up to 35°C gradually, and carry out the condensation reaction with heat preservation and stirring for 2h. During the reaction, solids are precipitated. , the temperature of the reaction solution was gradually lowered to about 5°C, and after stirring for 1 h, the reaction solution was filtered to remove salt components, and the filter cake was washed with 2 mL of acetone to finally obtain an acetone solution containing the corresponding intermediate compound of formula III for use.

[0051] At room temperature, put 3.84g of sodium hydroxide into another clean three-necked reaction flask, then slowly add 5mL of water and stir to dissolve the alkali completely. After the temperature of the aqueous solution...

Embodiment 2

[0054] Dissolve 2 g of the starting material 1-methyl-5-amino-4-ethoxycarbonylpyrazole in 30 mL of tetrahydrofuran at room temperature, and stir to dissolve. Then add 5.2 g of triphenylbromethane, stir to dissolve, then add 1.5 g of triethylamine dropwise, after the dropwise addition, heat up to 40°C and carry out the condensation reaction with heat preservation and stirring for 2.5 hours. During the reaction, solids are precipitated. After the end, the temperature of the reaction solution was gradually lowered to about 0°C, and after stirring for 1 h, the reaction solution was filtered to remove salt components, and then the filter cake was washed with 5 mL of tetrahydrofuran to finally obtain a tetrahydrofuran solution containing the corresponding intermediate compound of formula III. use.

[0055]At room temperature, put 4.0g of potassium hydroxide into another clean three-necked reaction flask, then slowly add 10mL of water and stir to dissolve the alkali completely. After...

Embodiment 3

[0058] The specific operation before the corresponding step C in this embodiment is the same as that of the embodiment 1, and will not be repeated here. Specifically, the compound of the intermediate product formula IV before the step C is obtained by using the implementation method of the corresponding operation in the embodiment 1, and then, The specific implementation of the next step is as follows:

[0059] Then take 3.8g (about 0.01mol) of the solid compound of formula IV and put it into another clean three-necked reaction flask, then add 60mL of dichloromethane, stir to dissolve, then add 3.0g of triethylamine, stir and mix evenly, and control the temperature at 20°C~25°C, dropwise add 2.0g (about 0.03mol) of sodium azide into the reaction liquid, after the dropwise addition, gradually raise the temperature of the system to 50°C, and carry out the rearrangement reaction with stirring and heat preservation for 3.0h, the reaction process is Gas generation, pay attention to...

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Abstract

The invention relates to a preparation method of a carbamyl amino pyrazol derived compound, belongs to the technical field of drug intermediates and aims to solve the problem that an existing synthetic route is complicated and is uneasy to operate. The preparation method of the carbamyl amino pyrazol derived compound comprises the steps that in the presence of an acid-binding agent, a compound shown in a formula II and triphenyl halomethane perform condensation reaction in an organic solvent to obtain an intermediate product compound shown in a formula III; then, in the presence of inorganic base, the compound shown in the formula III is subjected to ester hydrolysis reaction, and a compound shown in a formula IV is obtained; the compound and trinitride perform Curtius rearrangement reaction to obtain a compound shown in a formula V; the compound shown in the formula V and BoxEDA perform condensation reaction to obtain the carbamyl amino pyrazol derived compound. The preparation methodhas the advantages that raw materials are easy to obtain, a reaction route operation is simple, and the product yield and purity are high.

Description

technical field [0001] The invention relates to a preparation method of a carbamoylaminopyrazole derivative compound, belonging to the technical field of synthesis of pharmaceutical intermediates. Background technique [0002] Cefuroxime sulfate was developed by AstellasPharma and acquired its development rights by Calixa Therapeutics in 2007. In December 2009, Cubist Pharmaceuticals acquired CalixaTherapeutics and obtained the development and commercialization rights of ceftolozax sulfate (also known as CXA-101) and CXA-201 (ceftolozax / tazobactam) combination drug. Wherein, the structural formula of ceftriaxone sulfate is shown in the following formula VI: [0003] [0004] Cefolozane (Cefolozane) is a new type of intravenous administration of "fifth generation" cephalosporin antibiotics, which is well tolerated, has a broad antibacterial spectrum, and is effective against both Gram-positive and Gram-negative bacteria. The activity of Pseudomonas aeruginosa and multi-d...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D231/40
CPCC07D231/40
Inventor 周军荣刘青喜王天立池瀛江东周雅霜
Owner 浙江东邦药业有限公司
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