1-(3-Carboxy-2-pyridyl)-4-methyl-2-phenylpiperazine

Dark Yellow Solid

19.5 g (70.1 mmol) of the cyanopyridine compound was added to 25percent ethanol containing calcium hydroxide, and the mixture was stirred for about 20 hours at 100 ° C. After completion of the reaction, 390 mL of water was added, and the ethanol was distilled off under reduced pressure And the aqueous layer was extracted twice with 100 mL of dichloromethane 2 M hydrochloric acid was added dropwise to the aqueous layer to neutralize the pH to 6 to 7. The aqueous layer was extracted twice with 100 mL of ethyl acetate, After distilling off, the amorphous material was obtained, and the purity of the pyridinecarboxylic acid compound was confirmed by HPLC, and it was confirmed that the pyridinecarboxylic acid compound contained in this amorphous material was 18.4 g. 97.5 mL of ethyl acetate / methanol (mixed solvent of 80percent by volume / 20percent by volume) was added to this amorphous substance and heated to 60 ° C. (dissolution temperature) to obtain a mixed solution. The mixture was cooled to 5 ° C. at a cooling rate of 5 ° C./hour and cooled to 5 ° C. The mixture was stirred for about 4 hours at a temperature of 5 ° C. (ripening temperature) .Ethyl acetate / methanol percent / 20percent by volume mixed solvent) to obtain 14.7 g of a pyridinecarboxylic acid compound (yield: 71percent) (HPLC purity: 98.7percent)In a 5 L four-necked flask equipped with a stirrer, a thermometer, 300.0 g (1077.9 mmol) of 1- (3-cyanopyridyl-2) -4-methyl-2-phenylpiperazine, 6000 mL of ethanol solution was added and the mixture was stirred and heated to around 100 ° C.After reacting at around 100 ° C. for 4 hours, it was cooled to around 25 ° C. and 6000 mL of water was added.The ethanol was concentrated under reduced pressure, 2000 mL of dichloromethane was added to the obtained suspension, and the mixture was stirred for 15 minutes and then separated.This extraction operation was repeated twice.Further, 2 N hydrochloric acid aqueous solution was added to the obtained aqueous layer to neutralize the pH to 7.Subsequently, 1500 mL of chloroform was added and the mixture was stirred for 15 minutes, and then separated.The obtained organic solvent layer was mixed and concentrated under reduced pressure to obtainTo the residue, 1000 mL of ethanol was added and the mixture was warmed to around 70 ° C.The obtained solution was cooled to around 25 ° C. and stirred at about the same temperature for about 7 hours. The mixture was stirred for about 2 hours at the same temperature.The precipitated solids were separated by filtration and dried under reduced pressure at 80 ° C. for 10 hours to obtain 164.7 g (553.8 mmol) of a pyridine carboxylic acid compound (purity: 99.90percent, production yield: 51.4percent)A solution obtained by mixing 30 g of 2-(4-methyl-2-phenylpiperazin-1-yl)pyridine-3-carbonitrile and 590 ml of an ethanol solution of 25percent potassium hydroxide was heated to around 100 ° C followed by stirring for 4 hours. After cooling the reaction solution to around 25 ° C, 590 ml of water was added, ethanol was distilled off under reduced pressure, the obtained suspension was extracted twice with 200 ml of dichloromethane, and further the aqueous layer was neutralized to pH7 with 2N aqueous hydrochloric acid solution and extracted with chloroform, and the combined organic layer was obtained. To the residue obtained by distilling off the solvent from the organic layer under reduced pressure, 105 ml of ethanol was added, and the mixture was heated to about 70 ° C and stirred, and the obtained solution was cooled to about 25 ° C and stirred for 5 hours. The precipitated solid was collected by fractional filtration under reduced pressure, and the obtained wet body was dried under reduced pressure at 80 ° C for 10 hours to obtain 16 g (purity 99.50percent) of pyridine carboxylic acid.

Mirtazapine (M365000) impurity.

Molecular Weight:297.35
XLogP3:-0.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:3
Exact Mass:297.147726857
Monoisotopic Mass:297.147726857
Topological Polar Surface Area:56.7
Heavy Atom Count:22
Complexity:384
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes