61337-89-1

Usage

Uses

Used in Pharmaceutical Industry:
1-(3-Hydroxymethylpyridin-2-yl)-4-methyl-2-phenylpiperazine is used as an impurity in the production of Mirtazapine (M365000) for the treatment of major depressive disorder. As Mirtazapine Impurity B, it is essential to monitor and control its presence in the final product to ensure the safety and efficacy of the medication.
Additionally, due to its structural similarity to Mirtazapine, it may have potential applications in the development of new pharmaceutical compounds or as a research tool for understanding the mechanisms of action of antidepressants. However, further research and development would be required to explore these possibilities.

InChI:InChI=1/C17H21N3O/c1-19-10-11-20(17-15(13-21)8-5-9-18-17)16(12-19)14-6-3-2-4-7-14/h2-9,16,21H,10-13H2,1H3

Upstream product

• 6602-54-6 2-chloro-3-pyridinecarbonitrile 
• 10366-35-5 2-chloronicotinamide 
• 13362-26-0 2-aminopyridine-3-carboxylic acid ethyl ester 
• 61338-13-4 2-(4-methyl-2-phenyl-1-piperazinyl)-3-pyridinecarboxylic acid 
• 61337-88-0 3-cyano-2-(4-methyl-2-phenyl-1-piperazynyl)pyridine 
• 5271-27-2 1-methyl-3-phenylpiperazine 

Downstream Products

• 85650-52-8 Mirtazapine 
• 24219-97-4 mianserin 

Relevant academic research and scientific papers

A synthesis method of midanping

The invention discloses a method for synthesizing mirtazapine. According to the method, 2-halogenated nicotinonitrile is used as an initial compound, and 2-chloronicotinamide, 2-(4-methyl-2phenyl-1-piperazinyl)nicotinamide, 2-(4-methyl-2phenyl-1-piperazinyl)nicotinic acid, 1-(3-hydroxymethylpyridyl-2-)-4-methyl-2-phenylpiperazine and other intermediate products are sequentially synthesized to prepare the mirtazapine. Against the defects in a current mirtazapine synthesizing method, the process is improved, a new synthesizing route is designed, and a preparation method which is economical and is easy for practical operation is provided to mirtazapine synthesis. The method is suitable for large-scale industrial production.

MANUFACTURING METHOD OF MIRTAZAPINE

PROBLEM TO BE SOLVED: To provide a method capable of manufacturing mirtazapine useful as antidepressant at high quality and high manufacturing yield without needs for complicated purification operation. SOLUTION: Mirtazapine with largely suppressed by-production amount of impurities during reaction can be manufactured by reacting with use of sulfuric acid with concentration of 85.0% or more and less than 96.0% in a method for manufacturing mirtazapine by reacting 2-(4-methyl-2-phenyl)-1-piperazinyl)-3-pyridinemethanol and sulfuric acid. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPO&INPIT

MANUFACTURING METHOD OF MIRTAZAPINE

PROBLEM TO BE SOLVED: To provide a method for manufacturing mirtazapine useful as an antidepressant at high quality and high manufacturing yield. SOLUTION: Mirtazapine with reduced impurities is manufactured by crystallizing mirtazapine by using a mixed solvent of a good solvent selected from an alcohol solvent, a ketone solvent, an ether solvent and an ester solvent and a poor solvent selected from heptane and hexane, or a mixed solvent of a good solvent and a poor solvent in which a good solvent which is acetonitrile and a poor solvent which is water in a method of manufacturing mirtazapine by reacting 2-(4-methyl-2-phenyl-1-piperazinyl)-3-pyridinemethanol and sulfuric acid. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT

MANUFACTURING METHOD OF MIRTAZAPINE

PROBLEM TO BE SOLVED: To provide a method for manufacturing mirtazapine useful as an antidepressant at high quality and high manufacturing yield. SOLUTION: Mirtazapine with reduced impurities is manufactured by crystallizing mirtazapine by using a mixed solvent of a good solvent selected from ethanol, propanol, isopropanol, acetone, tetrahydrofuran and dioxane and a poor solvent which is water, or a mixed solvent of a good solvent selected from propanol and isopropanol and a poor solvent which is heptane in a method of manufacturing mirtazapine by reacting 2-(4-methyl-2-phenyl-1-piperazinyl)-3-pyridinemethanol and sulfuric acid. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT

METHOD FOR PRODUCING MIRTAZAPINE

PROBLEM TO BE SOLVED: To provide a method in which mirtazapine useful as an antidepressant can be produced at high quality as well as at high production yield. SOLUTION: In a method for producing mirtazapine by reacting 2-(4-methyl-2-phenylpiperazin-1-yl)-3-pyridinemethanol with sulfuric acid, when an alcohol solution of crude mirtazapine obtained as a concentrated residue of a toluene extraction liquid is subjected to activated carbon treatment, the amount of toluene is made 15 g or less with respect to 100 g of the alcohol solution, whereby the reduction efficiency of specific impurities during the activated carbon treatment can be improved, and as a result, mirtazapine with high quality can be produced. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT

METHOD FOR PRODUCING MIRTAZAPINE

PROBLEM TO BE SOLVED: To provide a method by which mirtazapine useful as an antidepressant drug can be produced with high quality and high production yield in the present invention. SOLUTION: A method for producing mirtazapine includes allowing 2-(4-methyl-2-phenyl-1-piperazinyl)-3-pyridinemethanol and sulfuric acid to react with each other by stirring and mixing in a reaction vessel including a stirring body. In the method for producing mirtazapine, the stirring and mixing are performed by setting a tip rate which is the rate of a tip of the stirring body in the stirring at 1.0 m/s or more. SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2018,JPOandINPIT

METHOD FOR PRODUCING 1-(3-HYDROXYMETHYL-PYRIDYL-2-)-2-PHENYL-4-METHYLPIPERAZINE

PROBLEM TO BE SOLVED: To provide a method in which a pyridine methanol compound (1-(3-hydroxymethyl-pyridyl-2-)-2-phenyl-4-methylpiperazine) represented by formula (1) which is a useful intermediate for mirtazapine used as an antipsychotic agent, can be produced with high purity and with high yield. SOLUTION: Provided is a method for producing pyridine methanol compound by reducing a pyridine carboxylic acid compound represented by formula (3) to produce a pyridine methanol compound represented by formula (1), followed by crystallizing the pyridine methanol compound using an ester-based solvent. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT

MANUFACTURING METHOD OF PYRIDINEMETHANOL COMPOUND AND MANUFACTURING METHOD OF MIRTAZAPINE

PROBLEM TO BE SOLVED: To provide a method capable of manufacturing a manufacturing intermediate of mirtazapine which is useful as an antidepressant at high yield and manufacturing high purity mirtazapine. SOLUTION: In a method for reacting 2-(4-methyl-2-phenyl-1-piperazinyl)-3-pyridinecarboxylic acid and hydrogenated bis(2-methoxyethoxy)aluminum sodium, manufacturing yield of 2-(4-methyl-2-phenyl-1-piperazinyl)-3-pyridine methanol is improved by washing a reaction mixture with alkali metal halide. Also in the method, by-production amount of dimer impurities during reaction can be suppressed and high quality mirtazapine can be manufactured in a method for reaction 2-(4-methyl-2-phenyl-1-piperazinyl)-3-pyridine methanol and sulfuric acid. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT

1-(3-CARBOXYPYRIDYL-2-)-2-PHENYL-4-METHYLPIPERAZINE HAVING CRYSTAL STRUCTURE AND METHOD FOR PRODUCING THE SAME

PROBLEM TO BE SOLVED: To provide a novel crystal form of pyridinecarboxylic acid compound having high solubility in an ether solvent, such as THF, which can be used in an industrial scale, and a method for producing a high-purity pyridinemethanol compound. SOLUTION: The present invention provides a 1-(3-carboxypyridyl-2-)-2-phenyl-4-methylpiperazine (pyridinecarboxylic acid compound) of novel crystalline form having a characteristic peak at least at 10.1°±0.2° and 13.9°±0.2° in 2θ, in X-ray diffraction using Cu-Kα rays, by crystallization in acetate ester and methanol solvent systems. SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2018,JPO&INPIT

A rice the nitrogen is mellow synthetic method

The invention discloses a 1-(3-hydroxymethylpyridine-2-yl)-4-methyl-2-phenylpiperazine synthesis method. The method includes: dissolving N-(2-chloroethyl)-N-methyl-alpha-chlorine-beta phenethylamine in mixed solution of water and a nonpolar solvent to obtain solution A, and dissolving 2-amino-3-hydroxymethylpyridine into a nonpolar solvent containing a small quantity of low carbon alcohols to obtain solution B; dripping the solution B into the solution A to obtain an intermediate by reaction, dissolving the intermediate into an anhydrous high-boiling-point polar solvent, and dripping into an anhydrous high-boiling-point polar solvent of inorganic iodides under inert gas shielding to realize reaction for obtaining 1-(3-hydroxymethylpyridine-2-yl)-4-methyl-2-phenylpiperazine. By two steps for synthesis of 1-(3-hydroxymethylpyridine-2-yl)-4-methyl-2-phenylpiperazine, oxidization of the intermediate due to direct high-temperature reaction can be avoided by specific solvent systems, and reaction stability and yield are improved.