61338-13-4

Usage

Uses

Mirtazapine (M365000) impurity.

InChI:InChI=1/C17H19N3O2/c1-19-10-11-20(15(12-19)13-6-3-2-4-7-13)16-14(17(21)22)8-5-9-18-16/h2-9,15H,10-12H2,1H3,(H,21,22)

Upstream product

• 6602-54-6 2-chloro-3-pyridinecarbonitrile 
• 5271-27-2 1-methyl-3-phenylpiperazine 
• 10366-35-5 2-chloronicotinamide 
• 61337-88-0 3-cyano-2-(4-methyl-2-phenyl-1-piperazynyl)pyridine 

Downstream Products

• 61337-89-1 2-(4-methyl-2-phenylpiperazin-1-yl)-pyridine-3-methanol 
• 85650-52-8 Mirtazapine 

Relevant academic research and scientific papers

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

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

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.

PRODUCTION METHOD OF 2-(4-METHYL-2-PHENYLPIPERAZIN-1-YL)PYRIDINE-3-METHANOL

PROBLEM TO BE SOLVED: To provide a method of producing high-purity 2-(4-methyl-2-phenylpyperadin-1-yl)pyridine-3-methanol efficiently with a content of a specified impurity reduced. SOLUTION: In reducing 2-(4-methyl-2-phenylpyperadin-1-yl)pyridine-3-carboxylic acid or its salt, a solution or suspension of a metal hydride is added to 2-(4-methyl-2-phenylpyperadin-1-yl)pyridine-3-carboxylic acid or its salt. COPYRIGHT: (C)2016,JPO&INPIT

PROCESS FOR THE PREPARATION OF 1- ( 3-HYDROXYMETHYLPYRID-2 -YL ) -2 -PHENYL-4-METHYLPIPERAZINE AND MIRTAZAPINE

Disclosed herein is a process for the manufacture of mirtazapine and intermediates useful in preparing mirtazapine which includes the reduction of 1-(3-carboxypyridyl-2)-4-methyl-2-phenylpiperazine with an organoaluminum hydride.

PROCESS FOR THE PREPARATION OF 1- ( 3-HYDROXYMETHYLPYRID-2 -YL ) -2 -PHENYL-4-METHYLPIPERAZINE AND MIRTAZAPINE

Disclosed herein is a process for the manufacture of mirtazapine and intermediates useful in preparing mirtazapine which includes the reduction of 1-(3-carboxypyridyl-2)- 4-methyl-2-phenylpiperazine with an organoaluminum hydride.

Novel synthesis and crystallization of piperazine ring-containing compounds

The present invention is directed to methods for the preparation of piperazine ring-containing compounds, particularly mirtazapine. According to the present invention, the mirtazapine intermediate 1-(3-carboxypyridyl-2)-4-methyl-2-phenyl-piperazine is made by hydrolyzing 1-(3-cyanopyridyl-2)-4-methyl-2-phenyl-piperazine with a base where the base is present in a ratio of up to about 12 moles of the base per one mole of 1-(3-cyanopyridyl-2)-4-methyl-2-phenyl-piperazine. The mirtazapine intermediate 1-(3-carboxypyridyl-2)-4-methyl-2-phenyl-piperazine may be made of hydrolyzing 1-(3-cyanopyridyl-2)-4-methyl-2-phenyl-piperazine with potassium hydroxide at a temperature of at least about 130° C. The method of the present invention also includes reacting 2-amino-3-hydroxymethyl pyridine with N-methyl-1-phenyl-2,2′-iminodiethyl chloride to form 1-(3-hydroxymethylpyridyl-2)-4-methyl-2-phenyl piperazine, and adding sulfuric acid to the 1-(3-hydroxymethylpyridyl-2)-phenyl-4-methylpiperazine to form mirtazapine. The present invention a recrystallization of mirtazapine from crude mirtazapine. The present invention also relates to crystalline adducts of mirtazapine and water, preferably containing up to about 3.5% by weight water, pharmaceutical compositions containing the crystalline adducts, and methods of treating depression by administering such compositions.

Synthesis of piperazine ring

A novel process for preparing a compound of the formula I: whereinR1 denotes substituted or unsubstituted alkyl, alkoxy, aryl, aryloxy or arylalkoxy; R2 denotes substituted or unsubstituted alkyl, alkoxy, aryl, aryloxy, arylalkoxy, tosyl, formyl, acetyl or amine; and R3 denotes substituted or unsubstituted alkyl, alkoxy, aryl, aryloxy or arylalkoxy is disclosed. These compounds are useful in the synthesis of the antidepressant mirtazapine and other tetracyclic compounds.

Novel method for the preparation of piperazine and its derivatives

A novel method for the synthesis of piperazine and its derivatives of formula 1, 1wherein R is selected from hydrogen, or a lower alkyl group having 1 to 6 carbon atoms or a phenylalkyl group the alkyl of which has 1 to 4 carbon atoms; R1 is selected from hydrogen, a methyl group, a phenyl group optionally substituted with an alkyl group having 1 to 6 carbon atoms, or a phenylalkyl group the alkyl of which has 1 to 4 carbon atoms; and R2 is selected from hydrogen, or a methyl group, or a fluoromethyl group; 2comprising the steps: a. reacting an ester of formula 11 with substituted or unsubstituted ethylenediamine of formula 7 to give 3,4-dehydropiperazine-2-one and its derivatives of formula 12, wherein R, R1, R2 are as defined above and R6 is a C1 to C4 linear or branched alkyl group; and b. reacting the 3,4-dehydro-piperazine-2-one and its derivatives of formula 12 with a reducing agent to yield the piperazine and its derivatives of formula 1.