Amezepine Chemical Properties

Boiling point:

411.6±34.0 °C(Predicted)

Density 

1.061±0.06 g/cm3(Predicted)

pka

10.26±0.10(Predicted)

Amezepine Usage And Synthesis

Originator

Amezepine,ZYF Pharm Chemical

Manufacturing Process

78.0 g 9-methoxycarbony-10-methylacridinium methosulphate salt (obtained according to a process analogous to that described by Rauhut et al. [J. Org. Chem.,(30, 3587 (1965)], 800 ml ethanol and 40 ml distilled water are mixed; then 80.0 g potassium borohydride are added over the course of 45 min, at room temperature. The mixture is agitated for 30 min, poure into a water-ice mixture, agitated for 2 h, and extracted with ether; the extract is dried by vacuum distillation. 51.0 g 9-methoxycarbonyl-10-methylacridan, melting point 106°C (recrystallized from isopropyl ether) are obtained.
250.0 g 1-dimethylamino-2-chloroethane hydrochloride and 250 ml water are mixed and cooled; 250 ml sodium hydroxide solution are added at a temperature below 10°C; the mixture is agitated for 15 min at 5°C and extracted with ether. The ethereal phases are washed with water and dried over magnesium sulfate; the ether is distilled off and the residue is redistilled. 130.0 g 1-dimethylamino-2-chloroethane, boiling point 106°-108°C, are obtained.
36.5 g 9-methoxycarbonyl-10-methylacridan and 1 L of toluene are mixed; 50 ml toluene are distilled off and the mixture is cooled. 5.56 g potassium are added at a temperature below +10°C; the mixture is agitated for 2 h at room temperature, refluxed for 30 min, and cooled.
A solution of 52.5 ml 1-dimethylamino-2-chloroethane in 200 ml toluene is added at a temperature below 20°C; the mixture is refluxed for 20 h and cooled, and 100 ml t-butanol are added. The mixture is agitated for 1 h at room temperature, 35 ml ethanol are added, and the mixture is again agitated for 30 min at room temperature. It is then extracted with 2 N hydrochloric acid; the acidic phases are washed with ether, made alkaline by the addition of sodium hydroxide solution, and extracted with ether; the ethereal phases are washed with water, dried over magnesium sulphate and then distilled to dryness under a vacuum. The residue is dissolved in 100 ml methanol; 300 ml of a saturated solution of fumaric acid in methanol are added; the methanol is distilled off and replaced by ethyl acetate.
Crystallization is allowed to commence and the mixture is cooled with ice for 30 min and suction-filtered; the precipitate is washed with water and dried. 37.0 g 9-(2-dimethylaminoethyl)-9-methoxycarbonyl-10-methylacridan fumarate are obtained, melting point 176°C (recrystallized from methanolethyl acetate).
50.0 g of the 9-(2-dimethylaminoethyl)-9-methoxycarbonyl-10-methylacridan fumarate are suspended in 500 ml water; the suspension is cooled and 30 ml sodium hydroxide solution are added. The mixture is extracted with dichloromethane and the organic phases are washed with water, dried over magnesium sulphate and then distilled to dryness under a vacuum 36.0 g 9- (2-dimethylaminoethyl)-9-methoxycarbonyl-10-methylacridan are obtained.
400 ml tetrahydrofuran are cooled and 20.0 g lithium aluminum hydride are added over the course of 15 min, followed by a solution of 36.0 g 9-(2- dimethylaminoethyl)-9-methoxycarbonyl-10-methylacridan in 400 ml tetrahydrofuran added over the course of 30 min. The mixture is refluxed for 2 h and cooled, and 200 ml tetrahydrofuran containing 20% water are added at a temperature below 0°C. The mixture is filtered, washed with dichloromethane, and distilled to dryness under a vacuum; the residue is dissolved in dichloromethane and the organic phases are washed with water, dried over magnesium sulfate, and concentrated, ethyl acetate being added to replace the dichloromethane. Crystallization is allowed to commence and the mixture is cooled with ice for 1 h, suction-filtered, washed with water, and dried.
24.5 g 9-(2-dimethylaminoethyl)-9-hydroxymethyl-10-methylacridan, melting point 150°C (recrystallized from dichloromethane - ethyl acetate) are obtained. On concentration of the mother liquors, a second yield of 1.6 g of product is obtained (total yield: 79%).
A mixture of 24.5 g 9-(2-dimethylaminoethyl)-9-hydroxymethyl-10- (methylacridan) 1 L of m-xylene and 125.0 g phosphorus pentoxide are refluxed for 3 h; the reacture mixture is cooled, poured on to ice, agitated for 15 min, alkaline by the addition of sodium hydroxide solution, and extracted with ethyl acetate; the organic phases are washed with water, dried over magnesium sulfate, and dried by vacuum distillation. The residue is dissolved in ether, filtered, and concentrated to a small volume; pentane is added with distillation to remove the ether. The mixture is filtered and concentrated to about 100 ml; crystallization is allowed to commence and the mixture is cooled with ice for 1 h and suction-filtered; the precipitate is washed with water and dried in vacua. After chromatographing on magnesium silicate, eluting with ether 16.0 g 5-methyl-10-(2-dimethylaminoethyl)-5Hdibenz[ b,f]azepine, melting point 78°C (recrystallized from pentane) are obtained (yield: 70%).
32.5 ml benzene and 5 ml ethyl chloroformate are mixed; a solution of 6.5 g 5-methyl-10-(2-dimethylaminoethyl)-5H-dibenz[b,f] azepine in 32.5 ml benzene are added; the mixture is refluxed for 5 h and cooled; ethyl acetate is added and the mixture is agitated in the presence of N-hydrochloric acid; the organic phase is decanted off, washed with water, dried over magnesium sulfate, and distilled to dryness under a vacuum; 5.0 g 5-methyl-10-[2-(Nethoxycarbonyl- N-methylamino)ethyl]-5H-dibenz[b,f]azepine are obtained. (Yield: 64%).
5.0 g caustic potash in 50 ml n-butanol is added to 5.0 g 5-methyl-10-[2-(Nethoxycarbonyl- N-methylamino)ethyl]-5H-dibenz[b,f]azepine; the mixture is agitated and refluxed for 20 h, and the butanol is distilled off in vacua; the residue is taken up with water, the mixture is extracted with ethyl acetate, and the organic phases are washed with water and dried over magnesium sulfate, and then distilled to dryness under vacuum; the residue is dissolved in 10 ml ether and the solution is chromatographed on magnesium silicate, eluting with ether, and distilled to dryness under a vacuum; 3.5 g crude 5- methyl-10-(2-methylamino-ethyl)-5H-dibenz[b,f] azepine are obtained.

Therapeutic Function

Antidepressant

Amezepine(60575-32-8)Related Product Information

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