Hydrochloride derivatives of 1-benzyl-4[(1-indanone)]- methylpiperidine

 

(57) Abstract:

Usage: as substances with antiacetylcholinesterase activity. The inventive product - hydrochloride derivatives of 1-benzyl-4-(1-indanone)methylpiperidine General formula 1, where R1is a hydrogen atom or a methoxy group, R2group-CH2-, n = 1 or 2.

The invention relates to new chemical compounds, namely hydrochloridum derivatives of 1-benzyl-4-indane)-methylpiperidine formula IHClwhere R1- H or methoxy;

R2is methylene;

n is an integer 1 or 2, which have a high and strictly selective antiacetylcholinesterase activity and can be used in medicine.

The aim of the invention is to develop new compounds that can be obtained using known methods produce similar compounds possess useful pharmaceutical properties.

P R I m e R 1. 1-benzyl-4-[2-[-1-indanone)-2-ylidene] ] ethylpiperidine hydrochloride.

0.32 g of 60% sodium hydride was washed with hexane and to this add 10 ml of THF. To this was added dropwise a solution 2,12 g of diethyl-(1-indanone-2-yl) phosphonate in 30 ml of THF at 0aboutC. the resulting mixture of prerestore 4,43 g of 1-benzyl-4-piperidinylidene in 10 ml of DMF. The resulting mixture was stirred at room temperature for 2 h and at 50aboutC for 2 h and then boiled for 2 hours while heating the mixture. To the reaction mixture is added methanol and 20 % sulfuric acid at 0aboutC. After 10 min after the addition the reaction mixture was alkalinized with an aqueous solution of sodium hydroxide and extracted with ethyl acetate. The organic phase is washed with saturated salt solution, dried over magnesium sulfate and concentrated in vacuo. The obtained residue is purified on a chromatographic column of silica gel (methylene chloride: methanol = 500 : 1). The eluate was concentrated in vacuo, and the residue is dissolved in methylene-chloride. To the resulting solution was added 10% solution of hydrochloric acid in ethyl acetate, and then concentrated in vacuo to obtain 0.73 g (yield 27 % ) specified in the title compounds. This also highlights of 1.37 g of diethyl(1-indanone-2-yl)phosphonate.

P R I m m e R 2. 1-benzyl-4-[2-[(1-indiano)-2-yl] ] ethylpiperidine (1).

of 0.37 g of 1-benzyl-4-[2-[(1-indanone)-2-ylidene] ] -ethylpiperidine dissolved in 10 ml of methanol, and then add 0.1 g of 5 % rhodium on coal. The resulting mixture hydronaut at room temperature under atmospheric pressure for 24 hours, the Catalyst otfit is the cosmology vacuum. The residue is purified through column chromatography (methylene chloride : methanol = = 200 : 1), the obtained eluate was concentrated in vacuo, and the residue is dissolved in methylene chloride. To the resulting solution was added 10% solution of hydrochloric acid in ethyl acetate, and then concentrated in vacuo to obtain crystals, which are recrystallized in isostasy methanol/IPE to obtain 0.33 g (yield 80 % ) specified in the title compound with the following characteristics:

So pl. 224-225aboutC.

WITH23H27Na HCl

Calculated, % : C 74,68; N 7,63; N 3,79.

Found, % : C 74,66; N. Of 7.65; N Of 3.77.

P R I m e R 3. 1-benzyl-4-[(5, 6-dimethoxy-1-indanone)-2-yl] -methylpiperidin-HYDR-ochloride (2) HCl0.4 g of 1-benzyl-4-[(5, 6-dimethoxy-1-indanone)-2-ylidene] -methylpiperidine dissolved in 16 ml of THF, and then added 0.04 g of 10 % palladium on coal. The resulting mixture hydronaut at room temperature under atmospheric pressure for 6 hours the Catalyst is filtered off and the filtrate was concentrated in vacuo. The residue is purified using a chromatographic column with silica gel (methylene chloride : methanol = 50 : 1). The obtained eluate was concentrated in vacuo, and the residue is dissolved in methylene chloride. To the resulting solution was added 10% is kristallisera from methanol/IPE, getting 0.36 g (yield 82 % ) specified in the procurement connection with the following properties:

So melting point: 211-212aboutC (with decomposition)

Calculated, % : C 69,30, N 7,27; N 3,37.

WITH24H29NO3HCl

Found, % : C 69,33; N 7,15; N 3,22.

Studied acetylcholinesterase inhibitory effect of compounds 1 and 2 in vitro. As the source of acetylcholinesterase took the homogenate of mouse brain. Inhibitory activity of acetylcholinesterase sample expressed in units of concentration for 50% inhibition (IC50). IR50compounds 1 and 2 respectively of 0.23 μm and 0,053 microns.

Thus, the compounds of the invention exhibit high antiacetylcholinesterase activity. (56) General organic chemistry. / Edited by Burton D. I. and Ellis D & D. so 5 Connection of phosphorus and sulfur. M. : Chemistry, 1983, S. 82.

Hydrochloride derivatives of 1-benzyl-4-(1-indanone)-methylpiperidine General formula

HCl/

where R1is hydrogen or a methoxy group;

R2group-CH2-;

n = 1 or 2.

 

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, , , , , , , , , , , .

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