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Preparation method of CCR5 antagonist

A technology of reducing agent and organic solvent, applied in the field of preparation of CCR5 antagonists, can solve problems to be improved, etc., and achieve the effects of ideal reaction efficiency, improved reaction speed and high utilization rate

Inactive Publication Date: 2015-08-26
HUBEI BIO PHARMA IND TECHCAL INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] Therefore, the current method for preparing compound 1 and compound 4 still needs to be improved

Method used

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  • Preparation method of CCR5 antagonist
  • Preparation method of CCR5 antagonist
  • Preparation method of CCR5 antagonist

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Embodiment 1: the preparation of the compound shown in formula 1

[0053]

[0054] 215 mg compound 2, 770 mg NH 4 OAc, 44 mg NaBH 3 CN and 3 milliliters of methanol were mixed, and the resulting reaction system was stirred and reacted at room temperature for 48 hours. After the disappearance of the starting material was detected by TLC, 120 microliters of concentrated hydrochloric acid was added to the reaction system to quench the reaction, and then the reaction mixture was concentrated under reduced pressure. Obtain a white solid, then dissolve the white solid in 25 ml of water, and adjust the pH value of the solution to about 10 with solid KOH, extract the aqueous phase with chloroform (16 ml, 8 ml) twice, combine the chloroform solution, add anhydrous sodium sulfate After drying and concentration, 194 mg of the compound represented by Formula 1 was obtained, with a yield of 89.8%, and a purity of 98.8% as determined by HPLC.

[0055] LCMS(ESI)m / z:216(M+1)

Embodiment 2

[0056] Embodiment 2: the preparation of compound shown in formula 1

[0057] 215 mg compound 2, 960 mg (NH 4 ) 2 CO 3 , 31.4 mg NaBH 3 CN and 3 milliliters of methanol were mixed, and then the resulting reaction system was stirred and reacted at room temperature for 45 hours. After the disappearance of the starting material was detected by TLC, 110 microliters of concentrated hydrochloric acid was added to the reaction system to quench the reaction, and then the reaction mixture was concentrated under reduced pressure. Obtain a white solid, then dissolve the white solid in 25 ml of water, and adjust the pH value of the solution to about 10 with solid KOH, extract the aqueous phase with chloroform (16 ml, 8 ml) twice, combine the chloroform solution, add anhydrous sodium sulfate After drying and concentration, 199 mg of the compound represented by Formula 1 was obtained, with a yield of 92.1%, and a purity of 97.0% as determined by HPLC.

Embodiment 3

[0058] Embodiment 3: the preparation of compound shown in formula 1

[0059] 215 mg compound 2, 770 mg NH 4 OAc, 31.4 mg NaBH 3 CN and 2 milliliters of methanol were mixed, and the resulting reaction system was stirred and reacted at room temperature for 48 hours. After the disappearance of the starting material was detected by TLC, 120 microliters of concentrated hydrochloric acid was added to the reaction system to quench the reaction, and then the reaction mixture was concentrated under reduced pressure. Obtain a white solid, then dissolve the white solid in 25 ml of water, and adjust the pH value of the solution to about 10 with solid KOH, extract the aqueous phase with chloroform (16 ml, 8 ml) twice, combine the chloroform solution, add anhydrous sodium sulfate After drying and concentration, 199 mg of the compound represented by Formula 1 was obtained, with a yield of 92.1%, and a purity of 98.5% as determined by HPLC.

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Abstract

The invention provides a preparation method of a CCR5 antagonist. A preparation method of a compound represented by a formula 1 of an intermediate body of the CCR5 antagonist comprises the following step: enabling a compound represented by a formula 2 to be subjected to a reduction amination reaction to obtain the compound represented by the formula 1. By virtue of the method, the compound represented by the formula 1 can be rapidly and effectively prepared and a target compound can be obtained by only one step; the steps are simple and reaction conditions are moderate and safe; the product purity is high and the industrialization is easy to realize.

Description

technical field [0001] The invention relates to the technical field of pharmacy, in particular to a preparation method of a CCR5 antagonist. Background technique [0002] Maraviroc (compound 4), developed by Pfizer of the United States, is a CCR5 receptor antagonist, and CCR5 receptor is the only way for HIV infection, so it can be used as a broad-spectrum anti-HIV drug. [0003] [0004] The drug was launched in the U.S. in August 2007 with dosage forms of tablets, 150mg and 300mg, and the trade name is Selzentry; in September of the same year, it was approved by the European Commission and launched in Europe with the trade name Celsentri. Maraviroc can selectively antagonize the co-receptor CCR5, and block the combination of HIV-1 envelope glycoprotein and CCR5 to prevent virus particles from invading and infecting host cells. In clinical treatment, Maraviro can significantly reduce the viral load in AIDS patients, and to a certain extent, reduce the mortality rate of ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D471/08
CPCC07D471/08
Inventor 王学海郭涤亮胡斌许勇杨仲文李莉娥乐洋黄璐田华肖强于静
Owner HUBEI BIO PHARMA IND TECHCAL INST
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