N,n-bis(1-adamantyl-1-ethylamine) hydrochloride and method for production thereof

FIELD: chemistry.

SUBSTANCE: invention relates to a novel compound - N,N-bis(1-adamantyl-1-ethylamine) hydrochloride of the structural formula I and a method for production thereof. Compound has biological activity and can be used as a component of a medicinal agent or as an impurity label of a medicinal agent as a standard sample in analytical chemistry of pharmaceutical preparations. A method of producing a compound of formula I includes a) obtaining 1-adamantyl-1-ethylamine from 1-adamantyl-1-ethylamine hydrochloride, b) obtaining a Schiff base of structural formula III by treating with a compound obtained at step (a) with acetyl adamantane, c) treating the Schiff base of formula III with a reducing agent to obtain bis(1-adamantyl-1-ethylamine) hydrochloride of formula I. The compound is characterised by a boiling point, IR, NMR and a mass spectrum data.

EFFECT: improved method.

2 cl, 8 dwg, 1 tbl, 3 ex

 

The claimed invention relates to organic chemistry, namely to methods for producing N,N-bis(1-adamantyl-1-ethylamine) hydrochloride of the General formula I:

The compound of formula I can be used as a component of antiviral drugs, and also as a marker of impurities in the sample medication.

A method of producing 1-aminoethyl-adamantane of formula II, which is the basis of biologically active substances influenza drug, widely used as a drug to fight influenza viruses of type a [1, 2].

The analysis technique for the synthesis of 1-aminoethyl-adamantane industrial method [3], it was found that in the process of synthesis of 1 - aminoethyl-adamantane possible occurrence of adverse reactions with the formation of Schiff bases, and with further exposure to reducing agents is formed by the product of structural formula I. the Formation of the product of structural formula I were confirmed by analysis of several samples of the substance 1-aminoethyl-adamantane hydrochloride, obtained industrially by the methods of chromatography-mass spectrometry and NMR.

On the chromatogram of the substance 1-aminoethyl-adamantane hydrochloride detected by admixture with Rt=2.35 (Fig. 1), in the mass spectrum of impurity (Fig. 2) ion is present with �molekulyarnoi weight 342,34 g/mol, which with an accuracy of 0.03 g/mol can be interpreted as quasimolecular ion with gross formula C24H41N.

With the aim of providing opportunities for quantitative determination of compounds of structural formula I in the samples was developed synthesis method of compound of structural formula I and held its synthesis.

The technical result of the invention is a method of obtaining new compounds N,N-bis(1-adamantyl-1-ethylamine) hydrochloride.

Brief description of the drawings:

Fig. 1. The chromatogram of the substance 1-aminoethyl-adamantane hydrochloride.

Fig. 2. The mass spectrum of the impurity found in the substance 1-aminoethyl adamantane hydrochloride Rt=2,35.

Fig. 3. The mass spectrum of the impurity found in the substance 1-aminoethyl adamantane mode activated dissociation collision (MS-MS of m/z 342+).

Fig. 4. The NMR spectrum1N bis(1-adamantyl-1-ethylamine) hydrochloride in CDCl3.

Fig. 5. The NMR spectrum13With bis(1-adamantyl-1-ethylamine) hydrochloride in CDCl3.

Fig. 6. The NMR spectrum1N bis(1-adamantyl-1-ethylamine) hydrochloride in D2O.

Fig. 7. Range IR bis(1-adamantyl-1-ethylamine) hydrochloride.

Fig. 8. The numbering of carbon atoms in the compound of formula I for identification in NMR spectra. Fig. 8 is only illustrative in nature is comfortable reading 1H-NMR spectrum.

The claimed invention is illustrated by the following examples:

Example 1. Obtaining 1-adamantyl-1-ethylamine (intermediate stage)

10 g of 1-adamantyl-1-ethylamine hydrochloride dissolved in 40 ml of water, then the obtained solution was added a solution of 4.07 g of sodium hydroxide in 20 ml of water.

The reaction mixture is incubated for 1 h at 65°C and vigorous stirring on a magnetic stirrer. The resulting emulsion was cooled for 0.5 h to room temperature. Then extracted with two portions of 30 ml of methylene chloride and the organic layer is separated in a separating funnel. The extract is dried over anhydrous sodium sulfate for 0.5 h. To separate the precipitate of the organic desiccant solution is filtered through a filter of SCHOTT under vacuum. Methylene chloride was distilled off on a rotary evaporator. Get 7,40 g of 1-adamantyl-1-ethylamine, without which involve cleaning to the next stage.

Example 2. Obtaining Schiff bases of structural formula III (intermediate stage)

The mixture to 3.56 g (0.02 mole) of acetylacetone and 3.58 g (0.02 mole) of 1-adamantyl-1-ethylamine was heated to boiling and maintained at this temperature for 1 h. the resulting alloy is treated with 60 ml of methanol and the resulting solid precipitate was dried under vacuum on the filter SCHOTT. Get 6,21 g of Schiff bases of structural formula III, cat�PoE without any treatment involved in the next stage.

Example 3. Obtaining bis(1-adamantyl-1-ethylamine) hydrochloride (final stage)

Obtained at the previous stage Schiff base is placed in 100 ml of methanol, with vigorous stirring in small portions add sodium borohydride. To initiate the process on a magnetic stirrer adjust the working surface temperature of 80°C. the Reaction mass is maintained at these conditions for 3 h. Then the reaction mass is transferred into 500 ml of water. The precipitate was filtered on the filter SCHOTT and dried. The dry residue was dissolved in 50 ml of chloroform and for 1 h, passed through a chloroform solution of dry hydrogen chloride. A chloroform solution of a compound of formula I is evaporated to dryness to give product which is then recrystallized from 5 ml of methylene chloride.

The result obtained 4.5 g of N,N-bis(1-adamantyl-1-ethylamine) hydrochloride. The final release of the compounds of structural formula I, taking into account the three stages, is 59%.

The obtained N,N-bis(1-adamantyl-1-ethylamine) hydrochloride has the following characteristics:

1. melting point 276°C (with decomposition);

2. the NMR spectrum1H in CDCl3(At 1.413 (6N, nl.C, C(24)N3With(25)N3), 1,72 (12H, nl.C, C(4)N2With(6)N2With(10)N2With(17)N2With(19)N2With(23) N2), 1,79 (6N, nl.C, C(2)H, C(8)H, C(9)H, C(15)H, C(21)H, C(22)H) 2,092 (6N, nl.C, C(3)H, C(5)H, C(7)H, C(16)H, C(18)H, C(20)H) 2,708 (2H, m, C(11)H, C(13)M), 7,31 (1H, c., NH));

3. the NMR spectrum13With in CDCl3(11,946 (2C, C(24)With(25)), 28,159 (6C, C(3)With(5)With(7), C(16)With(18)With(20)), 35,936 (2C, C(1)With(14)), 36,373 (6C, C(4)With(6)With(10)With(17), C(19)With(23)), 38,496 (6C, C(2)With(8)With(9)With(15)With(21)With(22)), 67,421 (2C, C(11)With(13)));

4. the NMR spectrum1N in D2O;

5. the mass spectrum with a molecular ion mass 342,34 g/mol;

6. The IR spectrum.

Table of peaks for Fig. 7
PositionIntensity
459.1788.640
600.8985.889
668.6887.591
752.0691.711
812.8790.802
850.7790.485
88.254
970.0689.506
983.4789.361
1026.0484.545
1049.7381.943
1070.4859.729
1094.3484.531
1177.1180.551
1198.7686.298
1254.6088.423
1317.5881.187
1349.4573.971
1375.1470.414
1394.4760.908
1419.1967.208
1447.0951.743
1598.2558.742
2342.0576.195
2360.6670.788
2478.97 78.389
2681.5964.633
2846.2927.276
2901.3717.156
3357.5972.734

References

1. Ershov F. I., Chizhov N. P., Tselakova E. B. Antiviral agents. SPb.: Science. 1993. 104 p.

2. Yakhontov, L. N., The R. G. Glushkov, Synthetic drugs. / M Medicine. 1983. P. 54-57.

3. Makariev S. M., Kaliteevsky V. V., Sheludyakov, V. D., Lebedev V. A., Lebedev A. B., Ustinova O. L. a Method of producing 1-(1'-adamantyl)ethylamine. RF patent №2118313 on Application No. 97106700 dated may 6, 1997

1. The compound of structural formula I

2. A method of producing compounds of structural formula I according to claim 1, which includes 3 stages, namely: a) preparation of 1-adamantyl-1-ethylamine hydrochloride from 1-adamantyl-1-ethylamine, b) by treating compound obtained in stage a) acetylaminophenol with obtaining Schiff bases of structural formula III

C) handling Schiff bases of the formula III regenerating agent with obtaining bis(1-adamantyl-1-ethylamine) hydrochloride of formula I.



 

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