N,n-bis(1-adamantyl-1-ethylamine) hydrochloride and method for production thereof
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 , 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|
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.
SUBSTANCE: invention relates to chemistry of adamantane derivatives, particularly an improved method of producing 2-(2-amino)alkyladamantanes of general formula (I), which can be of interest as intermediate products in synthesis of certain biologically active substances. The method of producing 2-(2-amino)alkyladamantanes of general formula (I): , where X=H, OH; R=H, CH3, C2H5, involves reducing 2-adamantylene acetonitrile with active hydrogen formed by reacting potassium hydroxide with aluminium contained in a nickel-aluminium (50/50) Raney alloy, with molar ratio of nitrile to hydrogen of 1:5-10. Reduction is carried out in a water-tetrahydrofuran medium.
EFFECT: method increases technological effectiveness of synthesis by changing conditions for implementing the method, enables to obtain a wider range of 2-(2-amino)alkyladamantane derivatives and also increases output of products to 90-96% and purity thereof.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to organic chemistry and medicine, and concerns new bicycloheptane amino derivatives, namely pharmaceutical salts of 2-(1-aminoethyl)bicyclo[2.2.1]heptane of formula (1) using them for treating influenza A.
EFFECT: compounds show high activity and low toxicity.
3 cl, 3 dwg, 4 tbl, 12 ex
SUBSTANCE: present invention refers to the componds of formula I and to physiologically endurable acid addtion salts of the mentioned compounds. The formula I compounds and their pharmaceutically acceptable salts can be used for preparation of pharmaceutical compositions in order to cure medical abnormalities responsive to dopamine D3 receptor ligand treatment.
EFFECT: preparation of pharmaceutical compositions in order to cure medical abnormalities responsive to dopamine D3 receptor ligand treatment.
47 cl, 2 tbl, 81 ex
SUBSTANCE: invention relates to a method for synthesis of N-(1-adamantylalkyl)cycloalkylamines of general formula:
1: X=- single bond, Z is cyclopentyl; 2: X=-CH2-, Z-cyclopentyl; 3: X=-CH-CH3, Z-cyclopentyl; 4: X=-CH-CH3, Z-cyclohexyl. Method involves reacting amino derivatives of adamantane with corresponding cyclic alcohols (cyclopentanol and cyclohexanol) in the presence of a Raney-Ni catalyst. The reaction is carried out in 8-16 hours with molar ratio of catalyst: adamantane-containing amine: alcohol equal to 0.21-0.6:1:6-14.8, which enables to obtain desired products in a single step with high selectivity and output of 53-91%.
EFFECT: improved method.
SUBSTANCE: present invention refers to the new naphtylene derivative having general formula (I-A) and to their pharmaceutically acceptable salts having the property of inhibition of the cytochrome ferment P450RAI (Cyp26) activity, to the pharmaceutic composition thereof and to the method of inhibition of cytochrome ferment P450RAI (Cyp26). , wherein X is selected from imidasolyl or triasolyl; R2 and R3, independently represent H, C1-10-alkyl; G1 is -NR72R82 or G1 and R3 taken together with attached carbon atom form 3-10-membered saturated ring or heterocyclic saturated ring containing N as heteroatom which is optionally substituted with substituting group R72, Z, R4b, R5b, Q1, R72, n2, n3 and n4 values are indicated in the formula of the invention.
EFFECT: present invention refers to the intermediates for compounds with general formula (I-A) and to their pharmaceutic salts thereof.
37 cl, 30 dwg, 7 tbl
< / BR>where R1=H, R2=H, CH3C2H5; R1=CH3, R2=CH3that are biologically active substances and compounds R1=H; R2=Me, Et, are substances of medicinal drugs Rimantadine" (1-(adamant-1-yl)ethylamine) and Adapalen" (1-(adamant-1-yl)Propylamine)
SUBSTANCE: invention relates to versions of an improved method of obtaining 4-aminodiphenylamine (ADPA) or its alkylated derivatives of the general formula (1) , where R1 represents H and R2 represents H or a lower alkyl. The method consists in the fact that carried out is the condensation of an aniline excess with nitrobenzene at a temperature of 30-150°C in the presence of a catalytic system, which includes as the catalyst a base, selected from hydroxides of alkali or alkali earth metals, and aliphatic heterochain polyethers, which are simultaneously a solvent and a cocatalyst, with the weight ratio of hydroxide to polyether of 1:5-20 with obtaining as the product a mixture of 4-nitrodiphenylamine and its salt, 4-nitrosodiphenylamine and its salt. The obtained mixture after neutralisation by acid is reduced in the presence of a catalyst Pd/c and hydrogen or is subjected to reducing alkylation in the presence of respective ketone. Reducing alkylation can be carried out in a medium of aliphatic heterochain polyethers or in the absence of aliphatic heterochain polyethers. This results in obtaining alkylated 4-ADPA derivatives. As polyethers usually used are polyethers, selected from ethers of polyethyleneglycol (PEG), polypropyleneglycol (PPG), polytrimethyleneoxide (PTMO), polytetrahydrofuran or monomethyl PEG ethers, monobutyl PPG ethers or their block-copolymers, such as PEG-PPG-PEG, PEG-PPG-PPG, PEG-PPG-PTMO, statistical polymer PEG-PPG. It is preferable to carry out condensation at a temperature of 60-80°C.
EFFECT: method makes it possible to simplify the process due to the repeated application of the catalyst with the preservation of the high output and quality of the obtained products.
7 cl, 4 dwg, 26 ex
SUBSTANCE: method involves catalytic telomerisation of butadiene with diethylamine in the presence of a catalyst based on cationic complexes of palladium (II) of general formula [(acac)Pd(L)2]BF4 (where acac is an acetylacetonate ligand, L=PPh3, P'Pr3, P"Bu3 P(p-Tol)3 or (L)2=diphosphine ligands, selected from bis(diphenylphosphino)methane(dppm), bis(diphenylphosphino)propane(dppp), bis(diphenylphosphino)butane(dppb), bis(diphenylphosphino)ferrocene(dppf)). The process is carried out in a substrate medium, specifically diethylamine and butadiene, at temperature of 50-90°C. The method enables to obtain N,N-diethylocta-2,7-diene-1-amine with selectivity of 99.9% from the overall mixture of reaction products with high process output which reaches 4180 g of product per 1 g Pd. The catalysts used are more readily available compared to those previously used for the process.
EFFECT: improved method.
1 tbl, 1 ex
SUBSTANCE: invention relates to catalysts of olefin hydroamination, their obtaining and application. Claimed is lithium-ligated hydroamination catalyst, which contains boron-beta-zeolites, molar ratio of boron atoms to lithium atoms constituting from 5:1 to 50:1. Also described is method of obtaining amines by converting ammonium or primary, respectively secondary amines with olefins at higher temperatures and pressure in presence of said hydroamination catalyst. Claimed is method of obtaining raw material for rubber industry: vulcanisation accelerators, methods of plant protection or pharmaceutical preparations with application of tert-butyl amine preliminarily obtained by method described above.
EFFECT: increased amine output.
10 cl, 1 tbl, 13 ex
SUBSTANCE: invention relates to a method of producing novel N-alkyl-3-methyl-4-nitrosoanilines of formula where R=i-Pr, cyclohexyl. The compounds can be used as modifiers and stabilisers of rubber mixtures and as starting compounds for synthesis of N-substituted n-phenylene diamines, which are used to produce a wide range of azo dyes and in colour photography. The method involves cyclocondensation of acetone and the corresponding amine with a product of nitrosation of 4,4-dimethoxybutan-2-one, which is first held in aqueous hydrochloric acid solution.
EFFECT: improved method.
SUBSTANCE: invention relates to an improved method of producing N1,N1,N4,N4-tetramethyl-2-butyne-1,4-diamine, which can be used in fine organic synthesis, particularly for producing scarce polycyclic compounds, as well as in synthesis of biologically active substances. The method involves reaction of bisamine with excess gaseous acetylene in the presence of a VO(acac)2 catalyst at temperature 65-75°C and atmospheric pressure for 1-3 hours.
EFFECT: method enables to obtain N1,N1,N4,N4-tetramethyl-2-butyne-1,4-diamine from available reactants with quantitative output of 76-98%.
1 tbl, 3 dwg, 1 ex
SUBSTANCE: invention relates to an improved method of producing at least one product from acrolein and acrylic acid via partial oxidation of propylene, where a) purified propane is converted at the first reaction step in the presence and/or absence of molecular oxygen, at least one dehydrogenation from a group comprising homogeneous dehydrogenation, heterogeneous catalytic dehydrogenation, homogeneous oxydehydrogenation and heterogeneous catalytic oxydehydrogenation, wherein a gaseous mixture 1 is obtained, which contains unconverted propane and the formed propylene, and b) optional separation from the total amount or partial amount of the gaseous mixture 1 of a partial amount of components other than propane and propylene contained therein, e.g., hydrogen, carbon monoxide, water vapour and/or optional conversion thereof to other compounds, e.g., water and carbon dioxide, and where a gaseous mixture 1' is obtained, which contains propane and propylene, and on at least one of the following reaction steps, c) the gaseous mixture 1 or gaseous mixture 1' or a mixture from the formed gaseous mixture 1' and the remaining gaseous mixture 1 as a component of a gaseous mixture 2 are subjected to heterogeneous catalytic gas-phase partial oxidation of propylene contained in gaseous mixture 1 and/or gaseous mixture 1', wherein a gaseous mixture 3 is obtained, which contains at least one product, d) on at least one separation step, the product is separated from gaseous mixture 3 and from the remaining residual gas, at least propane is returned to the first reaction step, where purified propane is obtained from crude propane which contains ≥90 wt % propane, ≤99 wt % propane and propylene, ≥100 ppm hydrocarbons, having 2 carbon atoms, and ≥100 ppm hydrocarbons, having 4 carbon atoms, under the condition that crude propane is fed into the fractionation column and purified propane is obtained higher than the feeding point under the condition that content of hydrocarbons having 2 carbon atoms, in wt %, in terms of the contained propane, in the purified propane is more than 100% of the corresponding content in crude propane and content of hydrocarbons having 4 carbon atoms, in wt %, in terms of content of propane, in the purified propane is at most 50% of the corresponding content in crude propane.
EFFECT: method enables to cut design expenses owing to no separation of C2-hydrocarbons during distillation.
48 cl, 1 ex
SUBSTANCE: present invention relates to versions of a method of purifying terbinafine from nonmetallic impurities, primarily a substance A of formula
, as well as to use of said methods to obtain purified terbinafine. One of the versions of the method involves molecular distillation of crude terbinafine in form of a free base and extraction the obtained purified terbinafine in form of a free base or acid-addition salt (method A). In another version (method B), crude terbinafine in form a free base undergoes molecular distillation combined with formation of a salt of the obtained product with simultaneous deposition of a purified trans-isomer, and the obtained highly pure terbinafine is extracted in form of a free base or acid addition salt.
EFFECT: method enables to obtain terbinafine containing less than approximately 5 ppm of substance A.
13 cl, 2 dwg, 6 ex
SUBSTANCE: method involves reaction of bisamine with 3-fold excess acetylene in the presence of a vanadyl acetylacetonate (VO(acac)2) catalyst in an argon atmosphere at temperature 70°C and atmospheric pressure for 3 hours, followed by addition of diisobutylaluminium hydride and stirring the reaction mixture for 4-6 hours at room temperature. The method enables to obtain N1,N1,N4,N4-tetramethyl-2-butene-1,4-diamine from available reagents with quantitative output of (82-97%).
EFFECT: high output of end product.
1 tbl, 3 dwg, 1 ex
SUBSTANCE: invention relates to an improved method of producing N1,N1,N4,N4-tetramethyl-2-butyne-1,4-diamine, which is used in synthesis of polycyclic compounds, as well as in synthesis of biologically active substances. The method involves reaction of N,N,N,N-tetramethylmethane-diamine with excess gaseous acetylene in the presence of a VO(acac)2 catalyst, taken in molar ratio of N,N,N,N-tetramethylmethane-diamine: (VO(acac)2) = 10 : (0.3-0.5), preferably 10:0.4, at temperature 65-75°C and atmospheric pressure for 1-3 hours.
EFFECT: method increases output of the desired product.
1 cl, 3 dwg, 1 tbl, 1 ex
SUBSTANCE: invention relates to an improved method of producing N,N,N,N-tetramethylalkadiynediamines, which can be used in fine organic synthesis, particularly for producing not easily accessible polycyclic compounds, as well as in synthesis of biologically active substances. Desired compounds are obtained from reacting diacetylene alkanes with excess N,N,N,N-tetramethylmethane diamine in the presence of a vanadyl acetylacetonate (VO(acac)2) catalyst, in molar ratio diacetylene alkane: N,N,N,N-tetramethylmethane diamine: VO(acac)2 = 10:(25-35):(0.2-0.4) in an argon atmosphere at temperature ranging from 70 to 100°C, mostly at 80°C, and atmospheric pressure for 4 to 8 hours.
EFFECT: method considerably simplifies synthesis schematic due to use of accessible initial reagents and significantly increases output of desired products, and allows for obtaining new and known compounds.
1 cl, 3 dwg, 1 tbl, 1 ex
SUBSTANCE: invention relates to N-adamantylbenzotriazole derivatives
and where R1 and R2 are hydrogen or a nitro group. The invention also relates to a method of producing the compound of formulae 1 and 2.
EFFECT: obtaining novel N-adamantylbenzotriazole derivatives which exhibit anti-influenza A virus activity.
3 cl, 5 ex
SUBSTANCE: drops possessing antiviral and immunomodulatory effects characterised by the fact that they represent a 95% ethanol infusion of wild strawberry leaves and fruit specified in: red raspberry fruit, mountain ash fruit, bilberry fruit, blood-red hawthorn fruit, cinnamon rose fruit; 15-25 mg of the substance in 1 ml of the infusion.
EFFECT: drops possess pronounced antiviral and immunomodulatory effects.
15 tbl, 5 ex