Derivatives aminocoumarin or their salts, processes for their preparation, composition for inhibiting the formation of lipoperoxide

 

(57) Abstract:

New derivatives of aminocoumarin General formula I, in which R1and R2represent a hydrogen atom, acyl group, alkoxycarbonyl group, alifaticescoe group or aromatic group; R3, R4and R5are optionally acylated hydroxyl, optionally substituted by an amino group, CNS group or aliphatic group, or two elements of R3, R4and R5can be linked together, forming a carbocyclic group; R6and R7represent aliphatic group and at least one of these elements has a methylene group in a-position; R8and R9represent a hydrogen atom, aliphatic group or aromatic group; or their salts, which are useful as drugs for the prevention and treatment of various diseases such as arteriosclerosis, hepatocyte, cerebrovascular disease and so on, 2 S. and 14 C.p. f-crystals, 1 table.

The subject invention is new derivatives of aminocoumarin or layers and pharmaceutical compositions containing them as active ingredient. In particular, the present invention OIE of lipoperoxide, which contain them as active ingredient and are used as drugs for prevention and treatment of various diseases such as arteriosclerosis, hepatopathy, cerebrovascular disease and similar diseases.

The prior art.

Since it was found that the formation of lipoperoxide in the body and the accompanying radical reaction have various harmful effects on humans resulting from the destruction of cell membranes, enzymatic disorders and similar phenomena, attempts were made to use antioxidants and inhibitors of education lipoperoxide as medicines. Currently the main inhibitors of education lipoperoxide are derivatives of natural antioxidants, such as vitamin C, vitamin E and similar products, and derivatives of phenol (Kenji of Fukuzawa, The Japanese Journal of Clinical Medicine, 46, 2 269 2 276, 1988). However, their main structural skeletons are very limited, and they do not always give satisfactory results in practical use. Therefore, it is highly desirable to obtain an inhibitor of education lipoperoxide having a new structure, which can effektivnosti, having inhibitory action against the formation of lipoperoxide, and drugs, inhibiting the formation of lipoperoxide which contain them as active ingredients.

Summary of the invention.

Given the above, the inventors have synthesized a number of new compounds and tested their anti-oxidant activity and inhibitory activity against the formation of lipoperoxide in order to achieve the above goals.

As a result, the authors of the present invention has been derived aminocoumarin with the new structure of the General formula (I):

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in which R1and R2have identical or different meanings and represent a hydrogen atom, acyl group, alokasikanlah group, optionally substituted alifaticescoe group or optionally substituted aromatic group; R3, R4and R5have identical or different meanings and represent optionally acylated hydroxyl group, optionally substituted by an amino group, optionally substituted CNS group, or optionally substituted aliphatic group, or two elements of R3, R46and R7is methylene in-position; and R8and R9have the same or different substitution and represent a hydrogen atom, optionally substituted aliphatic group or optionally substituted aromatic group, or its salt. In addition, it was found that the new compounds are useful drugs, having a strong inhibitory effect against the formation of lipoperoxide and similar action.

That is, the invention provides new derivatives aminocoumarin General formula (I) or their salts and pharmaceutical composition comprising them as an active ingredient.

A detailed description of the invention.

In the compound of General formula (I) acyl group represented by R1and R2includes acyl group derived from carboxylic acid, and acyl group derived from sulfonic acids, and similar groups. As the acyl group derived from carboxylic acid, specify C1-6acyl group (for example, formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl and so on). As the acyl group derived from sulfonic acids the Nile, phenylsulfonyl and similar groups. As alkoxycarbonyl group, represented by the elements of R1and R2you can specify the lowest alkoxycarbonyl group, CNS part of which contains 1 to 5 carbon atoms, such as methoxycarbonyl group, ethoxycarbonyl group and similar groups. Aliphatic group, expressed by the elements of R1and R2may be saturated or unsaturated group, examples of which include alkyl group, alkenylphenol group and alkylamino group. The alkyl group may be straight chain, branched chain or may be cyclic. Among alkyl groups are preferred lower alkyl group having from 1 to 6 carbon atoms, and examples of such groups include methyl, ethyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl and similar groups. As alkenylphenol group, represented by the elements of R1and R2preferred groups having from 2 to 6 carbon atoms, and examples of such groups include allyl, propenyl, Isopropenyl, 2-butenyl, 2,4 - butadienyl, 2-pentenyl and similar groups. As alkenylphenol group expressed by the elements of R1and R2, preferred is such a group. Substituents, which may include those aliphatic group, do not have any special restrictions. As an alternate, you can use any group that is usually used for the manufacture of medicines, and examples of such groups include hydroxyl, C1-3alkoxy (e.g. methoxy, ethoxy, n-propoxy or isopropoxy and so on), Arakelots (phenyl-C1-6alkoxy or naphthyl-C1-6alkyloxy, for example, benzyloxy, penetrate and so on), aryloxy (for example, phenyloxy, naphthyloxy, pyridyloxy, imidazolinone and so on), mercapto, C1-3alkylthio (for example, methylthio or ethylthio and so on), C1-3alkylsulfonyl (for example, methylsulphonyl or ethylsulfonyl and so on), C1-3alkylsulfonyl (for example, methylsulfinyl or ethylsulfinyl and so on), Uralkali (phenyl-C1-6alkylthio or naphthyl-C1-6alkylthio, for example, benzylthio, penicillia and so on), aralkylamines (phenyl - C1-6alkylsulfonyl or naphthyl-C1-6alkylsulfonyl, for example, bansilalpet, penetrameter and so on), aralkylamines (phenyl-C1-6alkylsulfonyl or naphthyl-C1-6alkylsulfonyl, for example, benzylmorphine, penecillin and so on), arieti (for example, phenylthio, naphthylthio, pyridylthio,polysulfonyl and so on), arylsulfonyl (for example, phenylsulfinyl, naphthylmethyl, pyridylsulfonyl or imidazolylalkyl and so on), amino, mono - and disubstituted an amino group which is substituted by 1 or 2 groups that represents C1-3alkyl, aralkyl (phenyl-C1-6alkyl or naphthyl - C1-6alkyl, and so on), and aryl (phenyl, naphthyl, pyridyl or imidazolyl and so on) (for example, methylamino, ethylamino, dimethylamino, benzylamino, phenylamino, pyridylamino and so on), halogen (e.g. chlorine or fluorine), the esterified carboxyl (for example, C2-5alkoxycarbonyl (for example, methoxycarbonyl, etoxycarbonyl and so on)), C2-3acyl (e.g. acetyl, propionyl and so on), C2-3acyloxy (for example, acetoxy, propionyloxy and so on), C2-3acylamide (for example, ndimethylacetamide and so on), C2-5alkoxycarbonyl (for example, methoxycarbonylamino, ethoxycarbonylethyl and so on ), the cyclic amino group (for example, pyrrolidino, morpholino, piperazine derivatives, and so on), a carboxyl group, karbamoilnuyu group and a similar group. These substituents are preferably used in quantities of from 1 to 2.

Aromatic group expressed by the elements of R1and R2is a phenyl group. Examples of the substituent of the phenyl group include an amino group, metroxylon, carboxyla, C1-5lower alkyl, C1-3lowest alkoxyl, C2-5the acyl, C1-3lower allylmercaptan and similar group. The number of substituents is not limited, but preferably it is from 1 to 3.

The group expressed NR1R2can substitute the benzene ring kumaran in any position of the ring, preferably in the position of the 5-th atom kumaran.

Preferably, one of the elements of R1and R2represented a hydrogen atom and the other is hydrogen atom, phenyl group, cyclic C1-6alkyl group with straight or branched chain.

If a hydroxyl group, represented by the elements of R3, R4and R5is acylated, the acyl group includes C2-5acyl group of the carboxylic acid with a straight or branched chain (for example, acetyl, propionyl, butyryl, isobutyryl and so on). If the amino group represented by the elements of R3, R4and R5has substituents, examples of such substituents include groups used optionally substituted aliphatic or aromatic groups, expressed by the elements of R1and R2. CNS group expressed by the elements of RThe 3D group, represents a cyclic alkyl group. As Deputy CNS group is used, for example, amino group, mono - or dialkylamino, substituted C1-3the lowest amino, halogen, hydroxyl, lower alkoxyl, lower allylmercaptan and similar group. Examples of aliphatic groups expressed by the elements of R3, R4and R5and their substituents include groups described in connection with the aliphatic group represented by R1and R2. Two elements of R3, R4and R5can be connected to each other to form optionally substituted carbocyclic group, and in this case, preference is given to 5 - or 6-membered carbocyclic group. Examples of the substituents include a C1-3alkyl group, a C1-3CNS group, hydroxyl group and similar groups.

R3, R4and R5preferably represent C1-6alkyl group with straight or branched chain, which may also be circular.

Examples of aliphatic groups expressed by the elements of R6and R7include groups described in connection with elements of R1and R2. Deputy alifatic the PU in addition to the deputies, described in connection with the aliphatic group represented by R1and R2. Optionally substituted aromatic groups and their substituents include groups described in connection with elements of R1and R2. In addition, at least one of the elements of R6and R7has a methylene group in the alpha position. In other words, R6and R7represent optionally substituted aliphatic group and at least one of these elements is a group of formula-CH2R' in which R' is hydrogen or R' together with the-CH2forms an optionally substituted aliphatic group. Examples of such aliphatic groups described in connection with elements of R6and R7.

Preferably, one of the elements of R6and R7was C1-6alkyl group with straight or branched chain, which may also be circular, and the other cyclic C1-6alkyl group with straight or branched chain, aracelio group (preferably phenyl-C1-6alkyl or naphthyl-C1-6alkyl, such as benzyl, phenethyl, phenylpropyl or similar group), which may be substituted by a group having from 1 to 5 heteroatoms (N, O, S). When is LTI, C1-3alkylsulfonyl, C1-3alkylsulfonyl, Uralkali, aralkylamines, aralkylamines, aaltio, arylsulfonyl, arylsulfonyl, mono - or disubstituted amino group, which is substituted by 1 or 2 groups that represents C1-3alkyl, aralkyl or aryl, and cyclic amino group.

The aliphatic group represented by R8and R9includes group described in connection with elements of R6and R7. Aromatic group, expressed by the elements of R8and R9includes group described in connection with elements of R1and R2.

Preferably, one of the elements of R8and R9represented a hydrogen atom, and the other phenyl group optionally substituted by a hydrogen atom, halogen or cyclic C1-6alkyl group with straight or branched chain.

The compound expressed by the General formula (I) can have a stereoisomer, depending on the particular type of substituent. The invention includes not only a single isomer, but their mix.

Salts of the compounds expressed by the General formula (I) are preferably pharmaceutically acceptable salts, with examples of pharmaceutically acceptable salts fluctuation acid, Hydrobromic acid and so on), phosphoric acid, sulfuric acid and the like acids, and with organic acids such as organic carboxylic acids (e.g. oxalic acid, phthalic acid, fumaric acid, maleic acid and so on), sulfonic acids (for example, methylsulfonate acid, benzolsulfonat acid and similar acids. In addition, if the compound (I) contains an acidic group such as carboxyl group and similar groups as substituents and their salts include inorganic basic salts formed with alkali metals (e.g. sodium, potassium, etc. or alkaline earth metal (e.g. magnesium) and similar metals, and salts formed with organic bases (for example, amines, such as dicyclohexylamine, triethylamine, 2,6-lutidine, and so on).

Further, the compound of formula (I) and their salts are defined simply as "compound (I)".

The compound (I) of the present invention can be obtained, for example, in accordance with the method determined by the scheme I:

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< / BR>
in which R1, R2, R3, R4, R5, R6, R7, R8and R9have the above values, -CH2R' cootek R'-C= turns into element of R6as a result of implementation of the above reaction with compound (III). In particular, R' represents a residue that forms the remainder R6together with the-CH2-. Examples of halogen, expressed by X include chlorine, bromine and the like halogen.

That is, the compound (I) can be obtained by cyclization of compound (II), preferably in the presence of (1) acid (2) molecules of halogen optionally together with a base or (3) percolate optionally together with base. The resulting product variant is exposed to the reaction unprotect, acylation reaction, the hydrogenation reaction, the reaction of the oxidant, the reaction Wittig, providing the lengthening of the carbon chain, or exchange reactions of substituents or combinations of two or more of these reactions. The compound (I) can also be obtained by condensation produced between the phenol (III) and a derivative of allyl alcohol, preferably in the presence acceptable acid catalyst, or by restoring nitro compounds (IV) or diazocompounds (V), after which the resulting product variant can be exposed to the reaction unprotect, reactions, acylation or alkylation reaction or combination of two or more lots, such as hydrochloric acid, Hydrobromic acid or similar acid at a temperature from room temperature up to 150oC, or the reaction is performed in a gaseous hydrogen chloride, ether complex of boron TRIFLUORIDE (BF3Et2O) or a similar compound in an organic solvent (e.g. chloroform, toluene, and so on), preferably at a temperature in the range -5oC to 150oC.

The reaction ring closure of halogen is carried out by reacting the compound (II) or its salt with bromine or similar element, preferably in organic solvents, such as galidupere (for example, chloroform, methylene chloride, and so on), acetic acid or a similar compound, optionally in the presence of such bases as sodium acetate, triethylamine or similar compound, at a temperature of from -5oC to 100oC.

The reaction ring closure by percolate is carried out by dissolving such percolate as metachlorobenzoic acid or a similar acid, in organic solvents, such as methylene chloride, optionally in the presence of such a base as triethylamine, at a temperature of from -10oC to 50oC.

The reaction Friedel is varicela, as dichloroethane, in the presence of sulfuric acid, triftormetilfullerenov acid or ether complex of boron TRIFLUORIDE at a temperature in the range of 0oC to 150oC.

The restoration of the nitro compounds is carried out by catalytic hydrogenation in the presence of a catalyst based on palladium carbon, by using such a metal as iron, the Tsing, tin or similar metal, in the presence of acid (e.g. hydrochloric acid, acetic acid and so on) or base (e.g. sodium hydroxide, and so on) or through the use of titanium trichloride in the presence of acid (e.g. acetic acid, and so on). Restoration of diazocompounds may be produced by similar catalytic hydrogenation or by using a reducing agent such as hydrosulfite sodium in water or an organic solvent when the temprature 0oC to 100oC.

Oxidation after the above reaction, ring closure is carried out using an oxidant derived from dimethylsulfoxide and oxalicacid, or oxidant such as chromium trioxide or similar connection variant in the presence of such a base as triethylamine, in an organic razminirovaniya (Wittig reaction) is carried out using lithium hydride, sodium hydroxide, sodium alcoholate, n-utility, diisopropylamide lithium or similar compound used as the base, in such a solvent as dimethylformamide, tetrahydrofuran, dimethoxyethane or similar connection. The reaction temperature preferably is in the range from -78oC to 80oC, and the reaction time is 0.5 to 24 hours.

Hydrogenation of the double bond of the target product can be obtained in the presence of such a catalyst as palladium carbon, in accordance with the known method.

Unprotect (hydrolysis) with a protected hydroxyl group can be performed under normal conditions of ester hydrolysis. If the product is unstable to oxygen in an alkaline medium, this reaction can be carried out in an argon atmosphere, which results in obtaining the target hydrolysate with a high output.

The acylation can be carried out with the necessary Alliluyeva agent (acid anhydride, galoyanized or similar compound), optionally in the presence of a basic catalyst, preferably sodium hydride, potassium carbonate, pyridine, triethylamine or similar compound) illecebrum solvent (for example, dimethylformamide, acetone, tetrahydrofuran). The reaction temperature is in the range from -10oC to 100oC, and the reaction time is from 10 minutes to 15 hours.

For the implementation of the exchange reaction of substituents derived 2-kaleidotile-2,3-dihydrobenzofuran, cyklinowanie halogen, is subjected to the interaction with the amine, thiol, alcohol or similar connection without the use of a solvent or in an organic solvent, such as dimethylformamide, toluene or a similar compound, optionally in the presence of a base (e.g. sodium hydride, and so on) at a temperature in the range -5oC to 200oC. If desired, as a reactor using an autoclave.

Examples of the acylation reaction include alkylation of an amino group or a hydroxyl group and a similar reaction. For alkylation can be used halogenated alkyl (examples of the halogen are chlorine, bromine and iodine), complex alkalemia esters of sulfuric acid or sulfonic acids, complex alkalemia esters of phosphoric acid and similar compounds. An alkylating agent is usually used in an equal or double amount, the reaction is carried out in the presence of inorganic bases (for example, hydroxylamine, pyridine and so on). The solvent used in this reaction, is not subject to any specific restrictions, you can use organic solvent such as tetrahydrofuran, dioxane, dimethylformamide, dimethylacetamide and the like compounds, or water. This reaction is usually carried out at a temperature in the range from room temperature to 100oC.

Starting compound (II), (III), (IV), (V) can be synthesized by a known method (for example, international publication W 086 / 05 781) essentially known method or in accordance with reference examples described below.

Thus obtained compound (I) can be distinguished using conventional methods of separation and purification, for example, extraction, chromatography, recrystallization and the like methods.

If the compound (I) is a mixture of diastereoisomers, each diastereoisomer variant can be selected with the help of the above methods of separation and purification.

If the compound (I) is optically active, each programalso and levogyrate isomer can be separated by conventional optical separation.

The compound (I) according to the invention improves funkzionirovaniye fatty acids (for example, linoleic acid, Y-linolenic acid, -linolenic acid, arachidonic acid, di - Homo-Y-linolenic acid, eicosapentaenoic acid), an inhibitory effect on the reaction lipoperoxide (antioxidant action); inhibitory effect on the formation of the metabolite 5-lipoxygenase (such as leukotrienes, 5-geroprotective acid (HPETE), 5-hydroxyeicosatetraenoic acid (HETE), lipotoxic, leukotoxin and so on); inhibitory effect on thromboxane-A2-synthetase; preserves and enhances the formation of prostaglandin-I2synthetase; has antagonism to receptors LTD4; acceptance of active oxygen and has a similar action.

Among these effects in compounds (I) according to the invention is the most powerful inhibitory action against the formation of lipoperoxide (antioxidant action).

The compound (I) has low toxicity and has little side effects.

Therefore, the compound (I) according to the invention has a therapeutic and preventive effect on various diseases in mammals (e.g. mice, rats, rabbits, dogs, monkeys, people, and so on), such as thrombosis, due to aggregation to vasospasm in the heart, lung, brain and kidney (e.g., myocardial infarction, bleeding in the brain, and so on ); neuropathy (e.g., Parkinson's disease, Alzheimer's disease Louis-Goering, muscular dystrophy, and so on); functional impairment caused by damage to the Central nervous system, such as the grass of the skull, spinal injury, etc dysmnesia or emotional disorders (disorders, followed by necrosis of nerve cells caused by hypoxia, brain injury, intracerebral hemorrhage, cerebral infarction, thrombosis of the cerebral vessels, and so on); convulsions and epilepsy, occur after intracerebral hemorrhage, cerebral infarction, operations on the brain or skull injury; jade; failure of the valve of the pulmonary artery; bronchial asthma; inflammation; arteriosclerosis; atherosclerosis; hepatitis; acute hepatitis; cirrhosis; allergic pneumonitis; immunodeficiency syndrome; a disease of the cardiovascular system caused by the defeat of enzymes, tissues, cells, etc. of a living organism by active oxygen compounds (e.g., superoxide, hydroxyl radical, and so on) (for example, myocardial infarction, intracerebral hemorrhage, brain swelling, jade and so on); fibroplastic reaction cloth is stannah funds as antithrombotic agent, anticonvulsant agent, an Antiasthmatic agent, an antiallergic agent, a means to improve the functioning of the cardiovascular system, serving the heart and brain, for the treatment of nephritis, the treatment for hepatitis, means for absorption of active oxygen, a means for regulating and improving the functioning arachnoidal cascade and similar tools.

The compound (I) can be administered orally or parenterally in the form as it is or in the form of pharmaceutical compositions (e.g., tablets, capsules, solutions, solutions for injections, suppositories), including well-known pharmaceutically acceptable carriers, fillers and similar materials. The dose may vary depending on the particular patient, the route of administration, state of disease, and similar factors. For example, in the case of oral administration to an adult patient suffering from a disease of the cardiovascular system, the connection of the present invention is normally administered 1-3 times daily in a dose of from 0.1 mg/kg to 20 mg/kg body weight, preferably from 0.2 mg/kg to 10 mg/kg body weight.

The invention is further illustrated in detail in the following with the o-2-benzyl-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran.

Sulfuric acid (15 ml) was added to a solution of 4-amino-2,3,5 - trimethylphenol (20,0 g, 0.12 mol) and 2-methyl-3-phenyl-2-propanol (25,0 g to 0.17 mol) in dichloromethane (100 ml), after which the mixture was heated under reflux for 1 hour. The reaction mixture was neutralized with saturated aqueous sodium bicarbonate solution, whereupon the product was extracted with ethyl acetate. The extract was washed with water and dried, and then drove the solvent. The residue was purified by chromatography on columns of silica gel (simple isopropyl ether and was led from the hexane with the formation of the target compound (7.2 g, yield 19,3%), the melting point of 68-69oC.

An NMR spectrum (CDCl3) d 1.38 (3H, c.), 2.06 (3H, c.), 2.10 (3H, c.), 2.16 (3H, c.), 2.80 (2H, broad singlet), 2.85 (2H, d, J=13.6 Hz), 3.08 (2H, d, J=13.6 Hz), 7.26 (5H, m).

Example 2. Hydrochloride 5-amino-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran.

4-Amino-2,3,5-trimethylphenol (2.0 g, 13,2 mmol) and 2-methyl-2-propanol (1,15 g 15,8 g) for 18 hours, heated under reflux in dichloromethane (20 ml) with sulfuric acid (2 ml). The reaction mixture was washed with saturated aqueous sodium bicarbonate solution, dried, and then concentrated. The residue was purified by chromatography on coloniali from a mixture of ethanol and simple isopropyl ester, in the resulting target compound (460 mg, yield of 14.4%), melting point 248-250oC. an NMR Spectrum (DMCO-d6) d 1.47 (6H, c. ), 2.08 (3H, c.), 2.18 (6H, c.), 3.03 (2H, c.), 9.80 (2H, broad singlet).

Example 3. Hydrochloride 5-amino-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran.

4 Formylamino-2,3,5-trimethyl-1-(2-methyl-2-propenyloxy)benzene (7,33 g, to 35.7 mmol) was dissolved in methanol (100 ml), and then to the solution was added concentrated hydrochloric acid (30 ml) under cooling with ice. After replacing the atmosphere in the flask with argon, the mixture was heated under reflux for 2 hours. The reaction mixture was cooled, then neutralized with an aqueous solution of sodium bicarbonate and was extracted with chloroform. The extract was washed with water, and then concentrated under reduced pressure. The residue was led from simple isopropyl ether, which allowed to obtain the target compound (6,40 g, yield of 99.2%). The connection part is transformed into the hydrochloride, and then was led from methanol, melting point 248 250oC (decomposition).

An NMR spectrum (DMCO-d6) d 1.41 (6H, c), 2.02 3H, c), 2.20 (6H c), 9.65 (2H, broad singlet).

Example 4. Hydrochloride 5-amino-2,2,4,6-tetramethyl-7-(2-methyl-1-propenyl)-2,3-dihydrobenzofuran (yield of 80.1% ), melting point 207 208oC (decomposition).

An NMR spectrum (MDCO-d6) d 1.39 (6H, c), 1.46 (3H, c), 1.86 (3H, c), 2.13 (3H, c), 2.21 (3H, c), 2.97 (2H, c), 5.90 (1H, c), 9738 (2H, broad singlet).

Example 5. 5-Acetylamino-2,2,6,7-tetramethyl-4-nitro-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized according to the procedure described in reference example 48 below (output 89,4% ), melting point 203oC (a mixture of dichloromethane and simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.48 (6H, c.), 2.15 (3H, c.), 2.18 (3H, c.), 2.19 (3H, c.), 3.29 (2H, c.), 7.79 (1H, broad singlet).

Example 6. 5-Acetylamino-2,2,4,7-tetramethyl-6-nitro-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 77,6%), melting point 203-204oC (a mixture of dichloromethane and simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.50 (6H, c.), 2.09 (3H, c.), 2.12 (3H, c.), 2.14 (3H, c.), 3.00 (2H, c.), 7.79 (1H, c.).

Example 7. The hydrochloride of 7-amino-2,2,4,5,6-pentamethyl-2,3-dihydrobenzofuran.

2,2,4,5,6-Pentamethyl-7-nitro-2,3-dihydrobenzofuran (310 mg, 1.3 mmol) was dissolved in ethanol (10 ml), after which the solution was subjected to catalytic restore what has koncentrirebuli. The residue was purified by chromatography on columns of silica gel (a mixture of hexane and simple isopropyl ether, 7:3), was transformed into the hydrochloride, and then was led from a mixture of ethanol and simple isopropyl ether, which allowed to obtain the target compound (170 mg, yield 53,3%), melting point 207-212oC.

An NMR spectrum (DMCO-d6) d 1.47 (6H, c.), 2.08 (3H, c.), 2.12 (3H, c.), 2.18 (3H, c.), 3.03 (2H, c.), 9.80 (2H, broad singlet).

Example 8. 5-Amino-2,2,4,6,7-pentamethyl-3-phenyl-2,3-dihydrobenzofuran.

2,2,4,5,6-Pentamethyl-5-nitro-3-phenyl-2,3-dihydrobenzofuran (2.0 g, 6.4 mmol) was dissolved in ethanol (15 ml), after which the solution was subjected to catalytic recovery in the presence of a catalyst based on a 5% palladium carbon (2.0 g). After filtration of the catalyst the filtrate was concentrated. The residue was purified by chromatography on columns of silica gel (simple isopropyl ether), and then was led from the hexane with the formation of the target compound (1,33 g, yield 73,6%), melting point 131 - 132oC.

An NMR spectrum (CDCl3) d 1.00 (3H, c.), 1.48 (3H, c.), 1.77 (3H, c.), 2.12 (3H, c. ), 2.19 (3H, c.), 3.10 (2H, broad singlet), 4.11 (1H, c.), 6.95 (2H, m), 7.20 (3H, m).

Example 9. 2-Amino-3-(4-forfinal)-2,2,4,6,7-pentamethyl-2,3 - Digi the above (yield of 70.2%), melting point 126-127oC.

An NMR spectrum (CDCl3) d 0.99 (3H, c.), 1.47 (3H, c.), 1.77 (3H, c.), 2.12 (3H, c. ), 2.18 (3H, c.), 3.10 (2H, broad singlet), 4.11 (1H, c.), 4.09 (1H, c.), 6.93 (4H, m).

Example 10. 5-Amino-3-(4-isopropylphenyl)-2,2,4,6,7-pentamethyl-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 85,0% ), melting point 134-135oC (hexane).

An NMR spectrum (CDCl3) d 1.00 (3H, c.), 1.22 (6H, d, J=6.8 Hz), 1.48 (3H, c. ), 1.78 (3H, c.), 2.13 (3H, c.), 2.19 (3H, c.), 2.85 (1H, septet, J=6.8 Hz), 3.10 (2H, broad singlet), 4.08 (1H, c.), 6.85 (2H, m), 7.07 (2H, d J=8.0 Hz).

Example 11. 2-Amino-2,2,4,6,7-pentamethyl-3-(3-pyridyl)-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 53,8% ), melting point 130-131oC (hexane).

An NMR spectrum (CDCl3) d 1.02 (3H, c.), 1.50 (3H, c.), 1.77 (3H, c.), 2.12 (3H, c. ), 2.19 (3H, c.), 3.04 (2H, broad singlet), 4.12 (1H, c.), 7.16 (2H, m), 8.36 (1H, m), 8.46 (1H, T. J=3.2 Hz).

Example 12. The dihydrochloride of 5-amino-3-(3-amino-4-dimethylaminophenyl)- 2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in the form of an amorphous product in accordance with the methodology description is 24 (1H, c.), 6.00-7.50 (5H, m), 9.85 (2H, broad singlet).

Example 13. Hydrochloride 5-amino-3-isopropyl-2,2,4,6,7-pentamethyl-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 76,6%), melting point 225-230oC (ethanol).

An NMR spectrum (DMCO-d6) d 0.70 (3H, d, J=6.6 Hz), 0.96 (3H, d, J=6.6 Hz), 1.21 (3H, c.), 1.57 (3H, c.), 1.62 (1H, m), 2.09 (3H, c.), 2.53 (3H, c.), 2.57 (3H, s), 2.76 (1H, d, J=2.8 Hz), 10.07 (2H, broad singlet).

Example 14. Hydrochloride 4,5-amino-2,2,6,7-tetramethyl-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 96.9 percent), melting point 248-251oC (ethanol).

An NMR spectrum (DMCO-d6) d 1.39 (6H, c.), 1.93 (3H, c.), 2.09 (3H, c.), 2.82 (2H, c.), 3.36 (4H, broad singlet).

Example 15. 5-Acetylamino-6-amino-2,2,4,7-tetramethyl-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 98.7 per cent), melting point 155-157oC (simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.44 (6H, c.), 1.82 and 2.23 (3H, c.), 2.00-2.05 (6H, c. ), 2.87 (2H, c.), 3.75 (2H, broad singlet), 6.40 and 6.62 (1H, broad singlet).

Example 16. 5-Acetylamino in accordance with the methodology described above (yield 91.4%), melting point 172-173oC (a mixture of ethanol and simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.46 (6H, c.), 1.83 and 2.23 (3H, c.), 2.05-2.09 (6H, m), 2.83 (2H, c.).

Example 17. 5-Amino-2,2,4,6,7-pentamethyl-3-(4-were)-2,3 - dihydrobenzofuran.

2,2,4,6,7-Pentamethyl-3-(4-were)-5-nitro-2,3 - dihydrobenzofuran (1.26 g, 3.9 mmol) was dissolved in methanol (30 ml). To the resulting solution was added zinc dust (1.3 g) and 1 n sodium hydroxide solution (15 ml), after which the mixture was heated under reflux for 3 hours. The insoluble substance was filtered and added water. This mixture was extracted with ethyl acetate. The extract was washed with water, dried, and then drove the solvent. The residue was purified by chromatography on columns of silica gel (a mixture of hexane and simple isopropyl ether, 95:5) and was led from the hexane with the formation of the target compound (710 mg, yield of 53.7%), melting point 119-120oC.

An NMR spectrum (CDCl3) d 1.00 (3H, c.), 1.47 (3H, c.), 1.78 (3H, c.), 2.13 (3H, c. ), 2.20 (3H, s), 2.31 (3H, c.), 3.20 (2H, broad singlet), 4.09 (1H, c.), 6.82 (2H, m), 7.10 (2H, m).

Example 18. 5-Amino-2,2,4,6,7-pentamethyl-3-(4-propylphenyl)-2,3 - dihydrobenzofuran.

Specified in the header with the 9oC (methanol).

An NMR spectrum (CDCl3) d 0.90 (3H, so J=7.2 Hz), 0.99 (3H, c.), 1.47 (3H, c. ), 1.60 (2H, sextet, J=7.2 Hz), 1.77 (3H, c.), 2.12 (3H, c.), 2.19 (3H, c. ), 2.54 (2H, so J=7.2 Hz), 3.10 (2H, broad singlet), 4.09 (1H, c.), 6.82 (2H, m), 7.03 (2H, d J=8.0 Hz).

Example 19. 5-Amino-2,2,4,6,7-pentamethyl-3-(4-pentylphenol)-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 55,6% ), melting point 67-68oC (methanol).

An NMR spectrum (CDCl3) d 0.87 (3H, so J=6.6 Hz), 1.00 (3H, c.), 1.31 (4H, m ), 1.47 (3H, c.), 1.58 (2H, m), 1.78 (3H, c.), 2.12 (3H, c.), 2.19 (3H, c. ), 2.55 (2H, so J=7.2 Hz), 3.20 (2H, broad singlet), 4.09 (1H, c.), 6.82 (2H, m), 7.03 (2H, d J=8.0 Hz).

Example 20. 5-Amino-2,2,4,6-tetramethyl-2-piperidinomethyl-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 82,1% ), melting point 60-61oC (simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.30-1.60 (6H, m), 1.42 (3H, c.), 2.07 (6H, c.), 2.10 (3H, c.), 2.35-2.65 (6H, m), 2.80 (1H, d, J=15.9 Hz), 3.10 (2H, broad singlet), 3.11 (doctor J=15.9 Hz).

Example 21. 5-Amino-2,4,6,7-tetramethyl-2-morpholinomethyl-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with metadirect NMR (CDCl3) d 1.42 (3H, c.), 2.07 (9H, c.), 2.40-2.70 (6H, m), 2.81 (1H, d, J=15.0 Hz), 3.13 (1H, d, J=15 Hz), 3.20 (2H, broad singlet), 3.67 (4H, so J=4.6 Hz).

Example 22. The dihydrochloride of 5-amino-2,4,6,7-tetramethyl-2-[2-(dimethylamino)- ethyl]-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in the form of an amorphous product in accordance with the methodology described above (yield 46,5%), melting point 200-203oC (decomposition) (a mixture of ethanol and simple isopropyl ether).

An NMR spectrum (DMCO-d6) d 1.41 (3H, c.), 2.06 (3H, c.), 2.17 (2H, m), 2.22 (3H, c. ), 2.24 (3H, c.), 2.74 (6H, s), 2.96 (1H, d, J=16.0 Hz), 3.11 (2H, m), 3.16 (1H, d, J=16.0 Hz), 9.78 (2H, broad singlet).

Example 23.

The dihydrochloride of 5-amino-2,4,6,7-tetramethyl-2-(2-piperidinoethyl)- 2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in the form of an amorphous product in accordance with the methodology described above (yield 41.9 per cent), the melting temperature of 260-270oC (decomposition) (a mixture of ethanol and simple isopropyl ether).

An NMR spectrum (DMCO-d6) d 1.41 (3H, c.), 1.76 (6H, m), 2.06 (3H, c.), 2.22 (3H, c. ), 2.23 (3H, c.), 2.23 (2H, m), 2.84 (4H, m), 2.95 (1H, d, J=15.8 Hz), 3.05 (2H, m), 3.15 (1H, d, J=15.8 Hz), 9.65 (2H, broad singlet).

Example 24. Oxalate 5-amino-2,2,4,6-tetramethyl-7-(dimethylamino)methyl-2,3 - digitalen is legido (1,61 g, 42.8 mmol) in ethanol (10 ml). This mixture was stirred at room temperature until, until it became homogeneous (within 30 min). This solution was added dropwise to a solution of 4-acetylamino-3,5-dimethyl-2-(2-methyl-2-propenyl)phenol (to 4.98 g, with 21.4 mmol) in ethanol (30 ml). The resulting mixture was heated under reflux for 3.5 hours in an argon atmosphere. The reaction mixture was cooled, and then concentrated under reduced pressure. The residue was purified by chromatography on columns of silica gel (a mixture of chloroform and methanol, 95: 5), which allowed to obtain the target compound (the 5.45 g, yield 87,7%) as a brown oil.

The obtained product was dissolved in methanol (60 ml) was added concentrated hydrochloric acid (20 ml). This mixture was heated under reflux for 1.5 hours in an argon atmosphere. After cooling, the reaction mixture was added to excess aqueous sodium bicarbonate solution, after which the mixture was extracted with chloroform. The extract was washed with water, dried and concentrated. The residue was purified by chromatography on columns of silica gel (a mixture of chloroform and methanol, 88:12) with the formation of the target product (a 4.86 g, yield 90,50%) as a brown oil.

oC in a sealed tube in an argon atmosphere. After cooling, the reaction mixture was added water and the mixture was extracted with chloroform. The extract was washed with water, dried, and then concentrated. The residue was purified by chromatography on columns of silica gel (a mixture of chloroform and methanol, 88:12) with the formation of the target product (1.70 g, yield of 41.5% ). Part of this product was converted to the salt of oxalic acid and then recrystallized from ethanol with the formation of the target compound, melting point 178-180oC (ethanol).

An NMR spectrum (DMCO-d6) d 1.39 (6H, c.), 2.02 (3H, c.), 2.07 (3H, c.), 2.74 (6H, m), 2.93 (2H, c.), 4.13 (2H, c.), 4.52 (4H, broad singlet).

Example 25. Oxalate 5-amino-2,2,4,6-tetramethyl-7-piperidinomethyl-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 47,9%-41,0%-55,7%), melting point 110-112oC (ethanol).

An NMR spectrum (DMCO-d6) d 1.44 (6H, c.), 1.62-1.80 (6H, m), 2.01 (3H, c.), 2.03 (3H, c. ), 2.99 (2H, c.), 3.11 (4H, broad singlet), 4.09 (2H, c.), 4.48 (4H, broad singlet).

Example 26 Oxalate 5-amino-2,2,4,6-tetramethyl-7-morpholinomethyl-2,3 - dihydrobenzofuran.

oC (ethanol).

An NMR spectrum (DMCO-d6) d 1.38 (6H, c.), 2.01 (3H, c.), 2.08 (3H, c.), 2.85 (4H, broad singlet), 2.90 (2H, c.), 3.68 (4H, broad singlet), 3.83 (2H, c.), 5.03 (4H, broad singlet).

Example 27. 5-Acetylamino-2-hydroxymethyl-2,2,4,6-tetramethyl-2,3 - dihydrobenzofuran.

4-Acetylamino-2,3,5-trimethy-6-(2-methyl-2-propenyl)phenol (2.0 g, 8.1 mmol) was dissolved in dichloromethane (20 ml). To this solution was slowly added metallocarborane acid (70% purity, 2.2 g, 8.9 mmol) under stirring and ice cooling. After the addition the reaction mixture was stirred at room temperature for 1 h and was added triethylamine (2 ml). The reaction mixture was washed with water, dried, and then concentrated. The residue was purified by chromatography on columns of silica gel (ethyl acetate) with the formation of the target compound (1.1 g, yield of 51.7%) in the form of butter.

An NMR spectrum (CDCl3) d 1.43 (3H, c.), 1.96 (1H, m), 2.07 (3H, c.), 2.09 (6H, c. ), 2.20 (3H, c.), 2.81 (1H, d, J=15.4 Hz), 3.16 (1H, d J=to 15.4 Hz), 3.63 (2H, m), 6.66 (1H, broad singlet).

Example 28. 5-Formylamino-2-hydroxymethyl-2,4,6,7-tetramethyl-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (you d 1.33 (3H, c.), 1.97 (3H, c.), 1.98 (3H, c.), 2.00 (3H, s), 2.73 (1H, d, J=15.4 Hz), 3.13 (1H, d J=to 15.4 Hz), 3.42 (2H, d, J= 5.8 Hz), 5.01 (1H, T. J=5.8 Hz), 7.83 (0,2 H, d, J=11,6 Hz), 8.21 (0,8 H, d, J=1.2 Hz), 9.05 (0,2 H, d, J=11,6 Hz), 9.20 (0,8 H, broad singlet).

Example 29. 2-methyl bromide-5-formylamino-2,4,6,7-tetramethyl-2,3 - dihydrobenzofuran.

4 Formylamino-2,3,5-trimethyl-6-(2-methyl-2-propenyl)-phenol (50 g, 0.21 mol) and sodium acetate (30.5 g, and 0.37 mol) was added to acetic acid (500 ml). To this mixture under stirring was added dropwise bromine (16.5 ml, 0.21 mol). After stirring the reaction medium within 30 minutes it was poured into a mixture of ice water and the resulting product was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium bicarbonate solution, dried, and then concentrated. The residue re-dissolved in ethyl acetate, and insoluble materials were filtered off. The filtrate was concentrated and to the residue was added a simple isopropyl ether. Precipitated crystals were filtered out, which allowed to obtain the target compound (44,0 g, yield 65,7%), melting point 157-158oC.

An NMR spectrum (CDCl3) d 1.61 (1,5 H, c.), 1.63 (1,5 H, c.), 2.09 (3H, s), 2.11 (3H, c. ), 2.13 (1,5 H, c.), 2.16 (1,5 H, c.), 2.93 (1H, d, J=15.8 Hz), 3.28 (0.5 H, d, J=15,8 Hz), 3.51 (1H, c.), 3.53 (1H, c.), 6.77 (0.5 H, broad singlet), 6.85 (0.5 H, d, J=12.0 Hz), 7.96 (0.5 H, d, J=12.0 Hz), 8.4 (0.5 H,p oxalicacid (0.45 ml, 4.7 mmol) in dichloromethane (10 ml) was cooled to -78oC, then under stirring was added dropwise dimethyl sulfoxide (1 ml). After stirring at the same temperature for 2 hours was added dropwise a solution of 5-acetylamino-2-hydroxymethyl - 2,4,6,7-tetramethyl-2,3-dihydrobenzofuran (1.1 g, 4.2 mmol) in dichloromethane (5 ml), after which the mixture was stirred for another 30 minutes. Was added triethylamine (3.5 ml) and the mixture was stirred for 10 minutes. The reaction mixture was washed with 1 N. a solution of hydrochloric acid and saturated aqueous sodium bicarbonate. The reaction mixture was dried, and then concentrated. The residue was purified by chromatography on columns of silica gel (ethyl acetate) with the formation of the target compounds (to 0.47 g, yield of 43.1%) in the form of butter.

An NMR spectrum (CDCl3) d 1.55 (3H, c.), 2.06 (3H, c.), 2.11 (3H, c.), 2.13 (3H, c. ), 2.21 (3H, c.), 2.94 (1H, d, J=15.8 Hz), 2.94 (1H, d J=15,8 Hz), 3.41 (1H, d J=15,8 Hz), 6.72 (1H, broad singlet).

Example 31. 2-Formyl-5-formylamino-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 25.5%).

An NMR spectrum (CDCl3) d 1.55 (1,5 H, c.), 1.57 (1,5 H, c.), 2.08 (3H, s), 2.12 (3H, c.), 2.15 (3H, c.), 2.94 (1H, d, J=15.4 Hz), 3.41 (0.5 H, the-Acetylamino-2,4,6,7-tetramethyl-2-styryl-2,3 - dihydrobenzofuran.

Suspension chloride benzyltriphenylphosphonium (0.7 g, 1.8 mmol) in tetrahydrofuran (10 ml) was cooled to -20oC and was added dropwise a solution of n-utility in hexane (1.6 M, of 1.12 ml, 1.8 mmol). The reaction mixture was stirred for 30 minutes and then was added a solution of 5-acetyl-2-formyl-2,4,6,7-tetramethyl-2,3 - dihydrobenzofuran (0.45 g, 1.7 mmol) in tetrahydrofuran (5 ml). The reaction mixture was stirred at room temperature for 30 minutes. To the reaction medium was added water and the resulting product was extracted with ethyl acetate. The extract was washed with water, dried, and then concentrated. The residue was purified by chromatography on columns of silica gel (a simple mixture of isopropyl ether and ethyl acetate, 1:1) with the formation of the target compound (0,44 g, yield 76,2%) as oil.

An NMR spectrum (CDCl3) d 1.55 (3H, c.), 1.87 (3H, c.), 1.98 (3H, s), 2.05 (3H, c. ), 2.19 (3H, c.), 2.94 (1H, d, J=15.4 Hz), 3.19 (1H, d J=to 15.4 Hz), 5.92 (1H, d J=12,8 Hz), 6.50 (1H, d J=12,8 Hz), 6.62 (1H, broad singlet), 7.25 (5H, m).

Example 33. (Z)-5-Acetylamino-2,4,6,7-tetramethyl-2-[2-(4-forfinal)- ethynyl]-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield 81,3%).

An NMR spectrum (CDCl

Example 34. Ethyl-3-[5-formylamino-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran - 2-yl]acrylate.

2-Formyl-5-formylamino-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran (1.0 g, 4.1 mmol), triethylphosphate (0,91 g, 4.1 mmol) and sodium hydride (60% purity, 162 mg, 5.1 mmol) was added to dimethylformamide, after which the mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with water and the resulting product was extracted with ethyl acetate. The extract was washed with water, dried, and then drove the solvent. The residue was purified by chromatography on columns of silica gel (a simple mixture of isopropyl ether and ethyl acetate, 1:1) with the formation of the target compound (0.5 g, yield 39,0%) as oil.

An NMR spectrum (CDCl3) d 1.29 (3H, so J=7.2 Hz), 1.60 (3H, c.), 2.06 (3H, c. ), 2.11 (1.5 H, s), 2.13 (1.H, c.), 2.15 (3H, c.), 2.17 (3H, c.), 3.05 (1H, d, J=15.4 Hz), 3.15 (1H, d J=to 15.4 Hz), 4.19 (2H, d, J=7.2 Hz), 6.02 (1H, d, J= 15.6 Hz), 6.92 (0.5 H, broad singlet), 6.95 (0.5 H, d, J=12.0 Hz), 7.02 (1H, d, J=15.6 Hz), 7.95 (0.5 H, d, J=12.0 Hz), 8.39 (0.5 H, d, J=1.6 Hz).

Example 35. 5-Acetylamino-2,4,6,7-tetramethyl-2-(2-phenylethyl)-2,3 - dihydrobenzofuran.

5% Palladium carbon (0.3 g) was added to a solution of (Z)-5 - Acetylamino-2,4,6,7-tetramethyl-2-styryl-2,3-dihydrobenzo the ATOR was filtered, and the filtrate was concentrated. The residue was purified by chromatography on columns of silica gel (a simple mixture of isopropyl ether and ethyl acetate, 1:1) with the formation of the target compound (0.95 g, yield 94,4%) as oil.

An NMR spectrum (CDCl3) d 1.48 (3H, c.), 2.02 (2H, m), 2.05 (3H, s), 2.09 (3H, c. ), 2.14 (3H, c.), 2.22 (3H, c.), 2.72 (3H, m), 2.89 (1H, d, J=15.4 Hz), 3.05 (1H, d, J=15.4 Hz), 7.10-7.30 (5H, m), 7.15 (1H, broad singlet).

Example 36. 5-Acetylamino-2-[2-(4-forfinal)ethyl]-2,4,6,7-tetramethyl-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield of 90.3%).

An NMR spectrum (CDCl3) d 1.47 (3H, c.), 1.98 (2H, m), 2.06 (3H, s), 2.10 (6H, c. ), 2.20 (3H, c.), 2.69 (2H, m), 2.90 (1H, d, J=15.4 Hz), 3.05 (1H, d J=to 15.4 Hz), 6.70 (1H, broad singlet), 6.95 (2H, m), 7.13 (2H, m).

Example 37. Hydrochloride 5-amino-7-(2-methylpropyl)-2,2,4,6-tetramethyl-2,3 - dihydrobenzofuran.

10% Palladium carbon (1.0 g) was added to a solution of 5-amino-7-(2-methyl-1-propenyl)-2,2,4,6-tetramethyl-2,3-dihydrobenzofuran (1.50 g, 6,11 mmol) in ethanol (100 ml) and the resulting mixture was heated under reflux for 3 hours in hydrogen atmosphere. The reaction mixture was cooled and filtered, and the filtrate was concentrated. The remainder of Kristie was turned into a hydrochloric salt, and then recrystallized from ethanol with the formation of the target compound (0,90 g, yield 51,9%), melting point 223-225oC (ethanol).

An NMR spectrum (DMCO-d6) d 0.85 (6H, d, J=6.6 Hz), 1.39 (6H, c.), 1.63-1.84 (1H, m), 2.21 (3H, c.), 2.22 (3H, c.), 2.38 (2H, d, J=7.2 Hz), 2.96 (2H, c. ), 9.54 (2H, broad singlet).

Example 38. 5-Formylamino-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran.

5-Amino-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran (1,00 g, to 4.87 mmol) was dissolved in formic acid (20 ml) and the resulting solution was heated under reflux for 48 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added a saturated solution of sodium bicarbonate, after which the mixture was extracted with chloroform. The extract was washed with saturated saline solution, dried, and then concentrated under reduced pressure. The residue was purified by chromatography on columns of silica gel (a mixture of chloroform and methanol, 97:3) with the formation of the target compound (1.06 g, yield of 83.3%). Part of this compound was recrystallized from a mixture of dichloromethane and simple isopropyl ether, which allowed us to obtain white prisms, melting point 177 - 179oC.

An NMR spectrum (CDCl3) d 1.46 (3H, c.), 1.48 (4H, c.), 2.09-2.16 (9H, m), 2.94 the Teal-2,3-dihydrobenzofuran.

To a solution of 5-amino-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran (1,00 g, to 4.87 mmol) and triethylamine (640 mg, 6,33 mmol) in tetrahydrofuran (20 ml) under ice cooling was added dropwise acetylchloride (460 mg, of 5.84 mmol). After the addition the mixture was stirred for 4 hours. To the reaction mixture was added water, after which it was extracted with chloroform. The extract was washed with saturated sodium bicarbonate solution and saturated saline solution, dried and concentrated. The residue was purified by chromatography on columns of silica gel (a mixture of chloroform and methanol, 97:3) with the formation of the target compound (920 mg, yield of 76.4%). Part of this compound was recrystallized from a mixture of dichloromethane and simple isopropyl ester, melting point 190oC (a mixture of dichloromethane and simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.46 (6H, c.), 1.76 and 2.21 (3H, c.), 2.06 (3H, c.), 2.09 (3H, c.), 2.14 (3H, c.), 2.93 (2H, c.), 6.63 (1H, broad singlet).

Example 40. 2,2,4,6,7-Pentamethyl-5-propionamido-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 99,8%), melting point 146oC (a mixture of dichloromethane and simple izopropilovogo.93 (2H, c.), 6.53 and 6.59 (1H, broad singlet).

Example 41. 5-Butylimino-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 70.8% ), the melting point of 136-138oC (a mixture of dichloromethane and simple isopropyl ether).

An NMR spectrum (CDCl3) d 0.87 and 1.05 (3H, so J=7.4 Hz), 1.46 and 1.51 (6H, c. ), 1.74-1.92 (2H, m), 2.05 and 2.09 (9H, m), 2.10-2.12 (2H, m), 2.39 (2H, so J=7.4 Hz), 2.93 (2H, c.), 6.52 and 6.62 (1H, m), 6.53 and 6.60 (1H, broad singlet).

Example 42. 5-Benzoylamino-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 84.5% ), melting point 263-265oC (a mixture of dichloromethane and simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.46 (6H, c.), 2.12 (6H, c.), 2.16 (3H, c.), 2.96 (2H, c.), 7.45 and 7.57 (3H, m), 7.90-7.96 (2H, m).

Example 43. 5-Isobutylamino-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 90.3% ), melting point 170-172oC (a mixture of dichloromethane and simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.30 (6H, d, J=7.0 Hz), 1.46 (6H the amino-2,2,4,6,7-pentamethyl-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 74,6% ), the melting point of 102-104oC (a mixture of pentane and simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.31 (3H, so J=7.4 Hz), 1.45 and 1.46 (6H, c.), 2.09 (6H, c. ), 2.13 (3H, c.), 2.93 (2H, c.), 4.20 (2H, K. J=7.4 Hz), 5.87 (1H, broad singlet).

Example 45. 5-Methanesulfonamido-2,2,4,6,7-pentamethyl-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 65,7% ), melting point 159-160oC (a mixture of dichloromethane and simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.47 (6H, c.), 2.10 (3H, c.), 2.25 (3H, c.), 2.28 (3H, c.), 2.93 (2H, c.), 3.03 (3H, c.), 5.40 (1H, c.).

Example 46. 2,2,4,6,7-Pentamethyl-5-(paratoluenesulfonyl)-2,3 - dihydrobenzofuran.

5-Amino-2,2,4,6,7-Pentamethyl-2,3-dihydrobenzofuran (2.00 g, 9,74 mmol) and paratoluenesulfonyl (2,04 g of 10.7 mmol) was dissolved in pyridine (30 ml) and was stirred at a temperature of 50oC for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in chloroform. The mixture was washed 1 N. a solution of hydrochloric acid and a saturated saline solution and dried, after ceciliages (a mixture of hexane and ethyl acetate, 97:3). The crude crystals are recrystallized from a mixture of dichloromethane and simple isopropyl ether with the formation of the target compounds (to 2.41 g, yield of 68.8%), melting point 219-220oC (a mixture of dichloromethane and simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.46 (6H, c.), 1.80 (3H, c.), 1.93 (3H, c.), 2.01 (3H, c. ), 2.43 (3H, c.), 2.87 (2H, c.), 5.81 (1H, c.), 7.24 (2H, d J=8.4 Hz), 7.60 (2H, d J=8.4 Hz).

Example 47. 5-Ethylamino-2-[2-(4-forfinal)ethyl]-2,4,6,7-tetramethyl-2,3 - dihydrobenzofuran.

To tetrahydrofuran (20 ml) was added 5-acetylamino-2-[2-(4 - forfinal)ethyl] -2,4,6,7-tetramethyl-2,3-dihydrobenzofuran (1.2 g, 3.4 mmol) and alumoweld lithium. This mixture was heated under reflux for 3 hours. The reaction mixture was poured into a mixture of ice water and the resulting product was extracted with ethyl acetate. The extract was washed with water and dried, and then drove the solvent. The residue was purified by chromatography on columns of silica gel (a mixture of isopropyl ether and ethyl acetate, 2:1) with the formation of the target compound (0,82 g, yield 71.2 percent) in the form of butter.

An NMR spectrum (CDCl3) d 1.21 (3H, so J=7.2 Hz), 1.47 (3H, c.), 1.98 (2H, m ), 2.11 (3H, c.), 2.14 (3H, c.), 2.19 (3H,c.), 2.70 (2H, m), 2.84 (2H, K. J=7.2 Hz), 2.85 (1H, broad singlet), 2.90 (1H, d, J=14,0 Hz), 3.02 (1H, d, J=14.0 Hz), ptx2">

To a solution of 5-amino-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran (9.00 g, and 38.6 mmol) in tetrahydrofuran (150 ml) under ice cooling was added alumoweld lithium (2,93 g, 77.2 mmol). This mixture was heated under reflux for 5 hours. After cooling the reaction mixture were added water (4.8 ml), then the mixture was filtered. The filtrate was concentrated under reduced pressure and the residue was purified by chromatography on columns of silica gel (a mixture of hexane and ethyl acetate, 9:1) the Purified product was converted into the hydrochloric salt, and the salt was recrystallized from a mixture of ethanol and simple ether, resulting in the target connection (a 4.03 g, yield 40.8 percent), melting point 205 - 208oC (a mixture of ethanol and simple ether).

An NMR spectrum (CDCl3) d 1.46 (6H, c.), 2.08 (3H, c.), 2.48 (6H, c.), 2.92 (2H, c.), 2.98-3.02 (3H, m), 10.57 (1H, broad singlet).

Example 49. Hydrochloride 5-ethylamino-2,2,4,6,7-pentamethyl-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield 34,0%).

An NMR spectrum (CDCl3) d 1.45 (6H, c.), 1.48 (3H, so J=8.4 Hz), 2.07 (3H, c. ), 2.47 (3H, c.), 2.48 (3H, c.), 2.91 (2H, c.), 3.35-3.48 (2H, m), 10.53 (1H, broad singlet).

the compound was synthesized in accordance with methods described above (yield 43,2% ), melting point 185-187oC (a mixture of ethanol and simple ether).

An NMR spectrum (CDCl3) d 0.92 (3H, so J=7.4 Hz), 1.45 (6H, c.), 1.93-2.06 (2H, m ), 2.07 (3H, c. ), 2.47 (3H, c.), 2.48 (3H, c.), 2.91 (2H, c.), 3.15-3.29 (2H, m), 10.54 (1H, broad singlet).

Example 51. Hydrochloride 5-Butylimino-2,2,4,6,7-pentamethyl-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 39.7% ), melting point 158-160oC (a mixture of ethanol and simple ether).

An NMR spectrum (CDCl3) d 0.86 (3H, so J=7.4 Hz), 1.23 - 1.38 (2H, m), 1.45 (6H, c. ), 1.91-2.06 (2H, m), 2.07 (3H, c.), 2.47 (3H, c.), 2.49 (2H, c.), 3.17-3.32 (2H, m), 10.57 (1H, broad singlet).

Example 52. Hydrochloride 5-benzylamino-2,2,4,6,7-pentamethyl-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 32,3% ), melting point 155-157oC (a mixture of ethanol and simple ether).

An NMR spectrum (CDCl3) d 1.44 (6H, c.), 2.02 (3H, c.), 2.10 (3H, c.), 2.20 (3H, c. ), 2.82 (2H, c.), 4.56 (2H, broad singlet), 7.19-7.32 (5H, m), at 10.89 (1H, broad singlet).

Example 53. Hydrochloride 2,2,4,6,7-pentamethyl-5-(2-methylpropyl)-amino-2,3 - dihydrobenzofuran.

Specified in the header SUB>) d 1.10 (6H, d, J=6.6 Hz), 1.45 (6H, c.), 2.05 (3H, c. ), 2.44 (3H, c.), 2.48 (3H, c.), 2.54-2.80 (1H, m), 2.90 (2H, c.), 2.93-3.04 (2H, m) 10.39 (1H, broad singlet).

Example 54. 5-Acetylamino-4-dimethylamino-2,2,4,7-tetramethyl-2,3 - dihydrobenzofuran.

Potassium carbonate (4.42 g, 32,0 mmol) and methyliodide (3,99 ml, and 63.9 mmol) was added to a solution of 5-acetylamino-2,2,4,7-tetramethyl-2,3 - dihydrobenzofuran (5.30 g, is 21.3 mmol) in dimethylformamide (100 ml) and the resulting mixture was stirred at room temperature for 3 hours. To the reaction mixture was added water, then this mixture was extracted with ethyl acetate. The extract was washed with water and dried, and then drove away the solvent under reduced pressure. The residue was purified by chromatography on columns of silica gel (a mixture of chloroform and methanol, 97:3) and recrystallized from a mixture of dichloromethane and simple isopropyl ether, which allowed to obtain the target compound (5,52 g, yield 93,6%), melting point 205 - 208oC (output 98,7%), melting point 186oC.

An NMR spectrum (CDCl3) d 1.44 (6H, c.), 2.09 (6H, c.), 2.21 (3H, c.), 2.67 (6H, c.), 3.09 (2H, s), 7.17 (1H, broad singlet).

Example 55. 5-Acetylamino-2,2,4,7-tetramethyl-6-dimethylamino-2,3 - dihydrobenzofuran.

Specified in the title compound was sintezirovany ether).

An NMR spectrum (CDCl3) d 1.46 (6H, c.), 2.04 (3H, c.), 2.10 (3H, c.), 2.20 (3H, c.), 2.78 (6H, c.), 2.90 (2H, s), 7.05 (1H, broad singlet).

Example 56. 5-Amino-2,2,4,7-tetramethyl-2-dimethylaminomethyl-2,3 - dihydrobenzofuran.

50% Aqueous solution of dimethylamine (20 ml) was added to a solution of 2 - methyl bromide-5-formylamino-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran (4.0 g, 12.8 mmol) in methanol (20 ml) and heated in an autoclave at a temperature of 160oC for 15 hours. After cooling, the reaction mixture was diluted with water, and the resulting product was extracted with ethyl acetate. The extract was washed with water and dried, and then drove the solvent. The residue was purified by chromatography on columns of silica gel (a mixture of chloroform and methanol, 95:5), and then recrystallized from simple isopropyl ether, which allowed to obtain the target compound (2.9 g, yield 91,2%), melting point 66-67oC.

An NMR spectrum (CDCl3) d 1.43 (3H, c.), 2.07 (3H, c.), 2.11 (3H, c.), 2.33 (6H, c. ), 2.50 (2H, s), 2.82 (1H, d, J=15.4 Hz), 3.10 (2H, broad singlet), 3.12 (1H, d, J=15.4 Hz).

Example 57. 5-Amino-2,4,6,7-tetramethyl-2-pyridiniomethyl-2,3 - dihydrobenzofuran.

To 2-methyl bromide-5-formylamino-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran (3.0 g, 9.6 mmol) was added pyrrolidine (20 ml) and the TES mixture was diluted with water, and the resulting product was extracted with ethyl acetate. The extract was washed with water and dried, and then drove the solvent. The residue was purified by chromatography on columns of silica gel (a mixture of chloroform and methanol 9: 1) and recrystallized from hexane with the formation of the target compound (2.2 g, yield 83,5%), the melting point of 85-86oC (decomposition).

An NMR spectrum (CDCl3) d 1.44 (3H, c.), 1.72 (4H, m), 2.06 (6H, c.), 2.10 (3H, c. ), 2.45-2.65 (4H, m), 2.68 (2H, s), 2.81 (1H, d, J=15.4 Hz), 3.16 (1H, d, J=15.4 Hz), 3.18 (2H, broad singlet).

Example 58. 5-Amino-2,4,6,7-tetramethyl-2-(4-methylpiperazine)methyl-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 76,2% ), melting point 76-77oC (simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.42 (3H, c.), 2.07 (6H, c.), 2.09 (3H, c.), 2.25 (3H, c. ), 2.40 (4H, m), 2.48 (1H, d, J=14.2 Hz), 2.58 (1H, d, J=14.2 Hz), 2.50-2.80 (4H, m), 2.80 (1H, d, J=14.4 Hz), 3.11 (1H, d, J=15.4 Hz), 3.25 (2H, broad singlet).

Example 59. 5-Amino-2,4,6,7-tetramethyl-2-[N-(2-piperidinoethyl)-aminomethyl] 2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 89.2%), the melting point of 102-104o<, is.), 1.73 (3H, broad singlet), 2.06 (3H, c.), 2.08 (3H, c.), 2.11 (3H, c.), 2.36-2.48 (7H, m), 2.75-2.79 (3H, m), 3.13-3.22 (1H, m).

Example 60. Hydrochloride 5-amino-2,4,6,7-tetramethyl-2-(N-phenyl-aminomethyl)- 2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 35.5%), melting point 162-168oC (a mixture of ethanol and simple ether).

An NMR spectrum (DMCO-d6) d 1.45 (3H, c.), 2.00 (3H, c.), 2.20 (3H, c.), 2.22 (3H, c. ), 2.90 (1H, d, J=16.4 Hz), 3.22 (1H, d, J=16.4 Hz), 3.31 (2H, c.), 6.61 (1H, T. J=7.8 Hz), 6.74 (2H, d J=7.8 Hz), 7.08 (2H, so J=7.8 Hz), 9.78 (3H, broad singlet).

Example 61. The dihydrochloride of 5-amino-2-(N-benzylamino)-2,4,6,7-tetramethyl - 2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 64,7%), melting point 228-232oC (a mixture of ethanol and simple ether).

An NMR spectrum (DMCO-d6) d 1.48 (3H, c.), 2.07 (3H, c.), 2.22 (3H, c.), 2.23 (3H, c. ), 2.93 (1H, d, J=16.2 Hz), 3.10 (2H, c.), 3.41 (1H, d, J=16.2 Hz), 4.19 (2H, c. ), 7,38-7,42 (3H, m), 7.60-7.65 (2H, m), 9.70 (3H, broad singlet).

Example 62. The dihydrochloride of 5-amino-2,4,6,7-tetramethyl-2-(N-phenethylamine)-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with methods,2 (3H, c.), 2.08 (3H, c.), 2.23 (3H, c.), 2.24 (3H, c. ), 2.95-3.50 (8H, c.), 7,22-7.38 (5H, m), 9.19-9.72 (3H, broad singlet).

Example 63. The dihydrochloride of 5-amino-2,4,6,7-tetramethyl-2-[N-(4 - phenylbutyl)aminomethyl]-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 72.6% ), the melting point of 201-202oC (a mixture of ethanol and simple ether).

An NMR spectrum (DMCO-d6) d 1.50 (3H, c.), 1.53-1.74 (4H, m), 2.07 (3H, c.), 2.24 (6H, c.), 2.59 (2H, so J=7.0 Hz), 2.91 - 3.00 (3H, m), 3.22 (2H, c.), 3.43 (1H, d, J=15.8 Hz), 7,16-7,29 (5H, m), 9.09-9.88 (3H, broad singlet).

Example 64. Trihydrochloride 5-amino-2,4,6,7-tetramethyl-2-[N-(3 - pyridylmethyl)aminomethyl]-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 54.6% ), melting point 208-213oC (a mixture of ethanol and simple ether).

An NMR spectrum (DMCO-d6) d 1.51 (3H, c.), 2.09 (3H, c.), 2.23 (6H, c.), 2.95 (1H, d, J=16.0 Hz), 3.28 (2H, c.), 3.50 (1H, d, J=16.0 Hz), 4.43 (2H, c.), of 7.97 (1H, double doublet, J=4.7 Hz, 8.0 Hz), 8.74 (1H, d, J=8.0 Hz), 8.88 (1H, d, J=5.4 Hz), 9.13 (1H, c.), 9.93 (3H, broad singlet).

Example 65. The dihydrochloride of 5-amino-2-(1-imidazolyl)methyl]-2,4,6,7-tetramethyl - 2,3-dihydrobenzofuran.

To a suspension of 2-methyl bromide-5-formylamino-2,4,6,7-tatrai was heated in an autoclave at a temperature of 200oC for 15 hours. The reaction mixture was washed with water, dried and the solvent drove away. The residue was dissolved in methanol (30 ml). To this mixture was added 6 N. aqueous sodium hydroxide solution, after which the resulting mixture was heated under reflux for 1 hour. This mixture was diluted with water and the resulting product was extracted with ethyl acetate. The extract was washed with water, dried and put away the solvent. The residue was purified by chromatography on columns of silica gel (a mixture of chloroform and methanol, 95:5). The purified product was converted into hloristovodorodnykh salt and then recrystallized from a mixture of ethanol and simple isopropyl ether with the formation of the target compound (1.3 g, yield of 37.8%), melting point 278-283oC (decomposition).

An NMR spectrum (DMCO-d6) d 1.41 (3H, c.), 2.08 (3H, c.), 2.24 (6H, c.), 3.09 (1H, d, J=16.2 Hz), 3.23 (1H, d, J=16.2 Hz), 4.54 (2H, c.), 7,66 (1H, d, J= 1.6 Hz), 7.73 (1H, d, J=1.6 Hz), 9.19 (1H, c.), 10.8 (2H, broad singlet).

Example 66. 5-Amino-2,4,6,7-tetramethyl-2-(4-phenylpiperazine)methyl-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 18.3% ), melting point 94-95oC (simple isopropyl ether).

Yo 67. 5-Amino-2,4,6,7-tetramethyl-2-(4-phenylpiperidine)methyl-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 57.5%), melting point 112-113oC (simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.47 (3H, c.), 1.75 (4H, m), 2.09 (6H, c.), 2.13 (3H, c. ), 2.15-2.50 (4H, m), 2.54 (1H, d, J=14.0 Hz), 2.63 (1H, d, J=14.0 Hz), 2.84 (1H, d, J=15.2 Hz), 2.99 (1H, m), 3.15 (1H, d, J=15.2 Hz), 3.19 (2H, broad singlet), 7.27 (5H, m).

Example 68. The dihydrochloride of 5-amino-2,4,6,7-tetramethyl-2-[4- (diphenylmethyl)piperidinomethyl]-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 17.7%), melting point 193-196oC (decomposition) (a mixture of ethanol and easy ethyl ester).

An NMR spectrum (DMCO-d6) d 1.50 (3H, c.), 1.99 (6H, c.), 2.21 (3H, c.), 3.03-3.51 (12H, m ), 5.20 (1H, broad singlet), 7.33-7.45 (6H, m), 7.68 (4H, broad singlet).

Example 69. Hydrochloride 5-amino-2-benzoyloxymethyl-2,4,6,7-tetramethyl-2,3 - dihydrobenzofuran.

Benzyl alcohol (20 ml) and sodium hydride (60% purity, 1.0 g, 25 mmol) was added to 2-methyl bromide-5-formylamino-2,4,6,7-tetramethyl - 2,3-dihydrobenzofuran (2.0 g, 6.4 mmol) and the resulting mixture was heated in the autoclave is vasica the product was extracted with ethyl acetate. The extract was washed with water, dried and put away the solvent. The residue was purified by chromatography on columns of silica gel (simple isopropyl ether). The purified product was converted into hloristovodorodnykh salt and then recrystallized from a mixture of ethanol and simple isopropyl ether with the formation of the target compound (0.68 g, yield of 30.5%), the melting temperature of 195-200oC.

An NMR spectrum (DMCO-d6) d 1.40 (3H, c.), 2.05 (3H, c.), 2.22 (6H, c.), 2.88 (1H, d, J=15.8 Hz), 3.17 (1H, d, J=15.8 Hz), 3.51 (2H, c.), 4.56 (2H, c.), 7.31 (5H, m), 9.71 (2H, broad singlet).

Example 70. Hydrochloride 5-Amino-2-methoxy-2,4,6,7-tetramethyl-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 49.6% ), melting point 180-182oC (a mixture of ethanol and simple isopropyl ether).

An NMR spectrum (DMCO-d6) d 1.37 (3H, c.), 2.04 (3H, c.), 2.22 (6H, c.), 2.85 (1H, d, J=16.0 Hz), 3.14 (1H, d, J=16.0 Hz), 3.31 (3H, c.), 3.43 (2H, c.), 9.77 (2H, broad singlet).

Example 71. 5-Amino-2,4,6,7-tetramethyl-2-[2-(dimethylamino)-ethoxymethyl] -2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in the form of an amorphous product in accordance with the methodology described above (yield 67,8%).

Example 72. 5-Formylamino-2,4,6,7-tetramethyl-2-phenylthiomethyl-2,3 - dihydrobenzofuran.

Sodium hydride (60% purity, 1.0 g, 21.1 mmol) was added to a solution of 2-methyl bromide-5-formylamino-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran (6.0 g, 19.2 mmol) and thiophenol in dimethylformamide (50 ml), after which the mixture was stirred at a temperature of 80oC for 1 hour in argon atmosphere. After cooling the reaction mixture the resulting product was extracted with ethyl acetate. The extract was washed with water, dried and put away the solvent. The residue was purified by chromatography on columns of silica gel (a simple mixture of isopropyl ether and ethyl acetate, 1:1), and then the purified product was recrystallized from a mixture of ethanol and simple isopropyl ether with the formation of the target compound (5,54 g, yield 83,35%), melting point 130-131oC.

An NMR spectrum (CDCl3) d 1.55 (1.5 H, c.), 1.56 (1.5 H, c.), 2.00 (3H, c.), 2.06 (1.5 H, c. ), 2.09 (1.5 H, c.), 2.11 (1.5 H, c.), 2.14 (1.5 H, c.), 2.91 (1H, d, J=15.8 Hz), 3.23 (0.5 H, d, J=15.8 Hz), 3.43 (0.5 H, d, J=15.8 Hz), 3.27 (2H, c. ), 6.74 (0.5 H, broad singlet), 6.84 (0.5 H, d, J=12.0 Hz), 7.15-7.40 (5H, m), 7.97 (0.5 H, d, J=12.0 Hz), 8.40 (0.5 H, 1.4 Hz).

Example 73. 2-(4-Forfinal)-thiomethyl-5-formylamino-2,4,6,7-tetramethyl-2,3 - dihydrobenzofuran.

Specified in the header suedeniam (CDCl3) d 1.53 (1.5 H, c.), 1.55 (1.5 H, c.), 2.05 (3H, c.), 2.06 (1.5 H, c. ), 2.11 (3H, c.), 2.14 (1.5 H, c.), 2.91 (1H, d, J=15.8 Hz), 3.21 (2H, c. ), 3.22 (0.5 H, d, J=15.8 Hz), 3.25 (0.5 H, d, J=15.8 Hz), 6.74 (0.5 H, broad singlet), 6.82 (0.5 H, d, J=12.2 Hz), 6.95 (2H, so J=9.0 Hz), 7.36 (2H, double doublet, J=5.2 Hz and 9.0 Hz), 7.97 (0.5 H, d, J=12.2 Hz), 8.40 (0.5 H, d, J=1.6 Hz).

Example 74. 5-Formylamino-2-(4-hydroxyphenyl)thiomethyl-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield 93.1% of).

An NMR spectrum (CDCl3) d 1.51 (1.5 H, c.), 1.53 (1.5 H, c.), 1.99 (3H, c.), 2.01 (1.5 H, c. ), 2.03 (3H, c.), 2.07 (1.5 H, c.), 2.10 (1.5 H, c.), 2.14 (1.5 H, c. ), 2.84 (0.5 H, d, J=15.4 Hz), 2.87 (0.5 H, d, J=15.4 Hz), 3.10 (0.5 H, d, J=15.8 Hz), 3.20 (0.5 H, d, J=15.8 Hz), 3.21 (0.5 H, d, J=15.8 Hz), 3.22 (0.5 H, d, J=15.4 Hz), 3.23 (0.5 H, d, J=15.8 Hz), 6.01 (0.5 H, broad singlet), 6.70 (0.5 H, broad singlet), 6.81 (0.5 H, broad singlet), 6.85 (0.5 H, broad singlet), 7.25 (2H, m), 7.95 (0.5 H, d, J=11.8 Hz), 8.39 (0.5 H, d, J=1.6 Hz).

Example 75. 5-Formylamino-2,4,6,7-tetramethyl-2-(1-methyl-2-imidazolyl)- thiomethyl-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield of 88.6%).

An NMR spectrum (CDCl3) d 1.53 (1.5 H, m), 1.55 (1.5 H, c.), 1.97 (3H, c.), 2.03 (1.5 H, c.), 2.04 (3H, c.), 2.10 (3H, c.), 2.14 (1.5 H, c.), 2.89 (1H, d, J= 15.6 Hz), 3.18 (0.5 H, d, J=15.6 Hz), 3.24 ( Hz), 8.37 (0.5 H, d, J=1.4 Hz).

Example 76. 2-(2-Benzothiazolyl)thiomethyl-5-formylamino-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 88,2%), melting point 190-192oC (simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.64 (3H, c.), 2.00 (3H, c.), 2.07 (1.5 H, c.), 2.10 (1.5 H, c.), 2.11 (1.5 H, c.), 2.14 (1.5 H, c.), 2.99 (1H, d, J=15.8 Hz), 3.27 (0.5 H, d, J=15.8 Hz), 3.29 (0.5 H, d, J=15.8 Hz), 3.78 (0.5 H, d, J=15.4 Hz), 3.79 (0.5 H, d, J=15.4 Hz), 3.87 (0.5 H, d, J=15.4 Hz), 3.88 (0.5 H, d, J=15.4 Hz), 6.73 (0.5 H, broad singlet), 6.75 (0.5 H, D. J=12.0 Hz), 7.20-7.50 (2H, m ), 7.70-7.85 (2H, m), 7.97 (0.5 H, d, J=12.0 Hz), 8.40 (0.5 H, d, J=1.6 Hz).

Example 77. 5-Formylamino-2,4,6,7-tetramethyl-2-(4-pyridyl)thiomethyl-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield 71.6 per cent).

An NMR spectrum (CDCl3) d 1.59 (1.5 H, c.), 1.61 (1.5 H, c.), 1.97 (3H, c.), 2.08 (1.5 H, c. ), 2.10 (1.5 H, c.), 2.13 (1.5 H, c.), 2.14 (1.5 H, c.), 2.98 (1H, d, J=16.0 Hz), 3.25 (0.5 H, d, J=16.0 Hz), 3.31 (2H, c.), 7.00 (0.5 H, d, J=12.0 Hz), 7.05 (0.5 H, broad singlet), 7.05 (0.5 H, broad singlet), 7.17 (2H, double doublet, J= 1.6 Hz and 6.2 Hz), 7.98 (0.5 H, d, J=12.0 Hz), 8.36 (2H, double doublet, J=1.6 Hz and 6.2 Hz), 8.37 (0.5 H, d, J=1.6 Hz).

Example 78. 2-Benzyldimethyl-5-formylamino-2,4,6,7-tetramethyl-2,3 - accordance with the methodology described above (yield 83.5 per cent).

An NMR spectrum (CDCl3) d 1.49 (3H, c.), 1.50 (1.5 H, c.), 2.08 (1.5 H, c.), 2.12 (6H, c.), 2.16 (1.5 H, c.), 2.71 (1H, d, J=13.4 Hz), 2.77 (1H, d, J=13.4 Hz), 2.86 (1H, d, J=15.0 Hz), 3.18 (1H, d, J=15.0 Hz), 3.74 (1H, d, J=13.2 Hz), 3.18 (1H, d, J=13.2 Hz), 6.76 (0.5 H, broad singlet), 6.87 (0.5 H, d, J= 12.0 Hz), 7.30 (5H, m), 7.98 (0.5 H, D. J=12.0 Hz), 8.40 (0.5 H, d, J=1.4 Hz).

Example 79. 5-Formylamino-2,4,6,7-tetramethyl-2-propylthiouracil-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield 93,0%).

An NMR spectrum (CDCl3) d 0.96 (3H, so J=7.4 Hz), 1.52 (1.5 H, c.), 1.54 (1.5 H, c.), 1.60 (2H, m), 2.08 (3H, c.), 2.10 (1.5 H, c.), 2.12 (1.5 H, c.), 2.13 (1.5 H, c.), 2.16 (1.5 H, c.), 2.58 (2H, double triplet, J=1.2 Hz and 7.2 Hz), 2.82 (1H, c.), 2.84 (1H, c.), 2.89 (1H, d, J=15.8 Hz), 3.22 (0.5 H, d, J= 15.8 Hz), 3.24 (0.5 H, d, J=15.8 Hz), 6.77 (0.5 H, broad singlet), 6.85 (0.5 H, d, J=12.0 Hz), 7.97 (0.5 H, d, J=12.0 Hz), 8.40 (0.5 H, d, J=1.6 Hz).

Example 80. 5-Formylamino-2-(2-hydroxyethyl)thiomethyl-2,4,6,7-tetramethyl - 2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield 57,2%).

An NMR spectrum (CDCl3) d 1.52 (1.5 H, c.), 1.54 (1.5 H, c.), 2.09 (3H, c.), 2.11 (1.5 H, c. ), 2.12 (1.5 H, c.), 2.13 (1.5 H, c.), 2.16 (1.5 H, c.), 2.29 (0.5 H, so J=6.4 Hz), 2.35 (0.5 H, so J=6.4 Hz), 2.80 (2H, double triplet, J= 7.2 Hz and J=1.2 Hz), 2.87 kg), 7.97 (0.5 H, d, J=12.0 Hz), 8.38 (0.5 H, d, J=1.4 Hz).

Example 81. 3-[(5-Formylamino-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran-2 - yl)methylthio] propionic acid.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield 94.7 percent).

An NMR spectrum (CDCl3) d 1.52 (1.5 H, c.), 1.54 (1.5 H, c.), 2.08 (3H, c.), 2.09 (3H, c. ), 2.12 (1.5 H, c.), 2.14 (1.5 H, c.), 2.64 (2H, so J=7.0 Hz), 2.86 (2H, so J=7.0 Hz), 2.87 (2H, c.), 2.90 (1H, d, J=15.4 Hz), 3.22 (1H, d, J=15.4 Hz), 6.50 (0.5 H, broad singlet), 6.95 (0.5 H, broad singlet), 7.96 (0.5 H, broad singlet), 8.38 (0.5 H, d, J=1.6 Hz).

Example 82. 5-Formylamino-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran-2-yl - phenylsulfanyl.

5-Formylamino-2,4,6,7-tetramethyl-2-phenylthiomethyl-2,3 - dihydrobenzofuran (2.3 g, 6.7 mmol) was dissolved in methanol (20 ml). To this solution was added 1 M aqueous solution of metaperiodate sodium (20 ml) and the resulting mixture was stirred for 3 hours. The reaction mixture was diluted with water, and the resulting product was extracted with ethyl acetate. The extract was washed with water, dried and put away the solvent. The residue was led from a mixture of ethyl acetate and simple isopropyl ether with the formation of the target compound (1.54 g, yield 64,0% ), melting point 112-115oC (decomposition).

The .96 (0.25 H, D. J=12.0 Hz), 7.99 (0.25 H, d, J=12.0 Hz), 8.40 (0.25 H, d, J=1.4 Hz), 8.42 (0.25 H, d, J=1.4 Hz).

Example 83. 5-Formylamino-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran-2-yl - phenylsulfonyl.

5-Formylamino-2,4,6,7-tetramethyl-2-phenylthiomethyl-2,3-dihydrobenzofuran (2.1 g, 6.2 mmol) was dissolved in methanol (20 ml). To this solution was added 2 M aqueous solution of metaperiodate sodium and the resulting mixture was heated under reflux for 3 hours. The reaction mixture was diluted with water, and the resulting product was extracted with ethyl acetate. The extract was washed with water, dried and put away the solvent. The residue was led from a mixture of ethyl acetate and simple isopropyl ether with the formation of the target compound (1.40 g, yield 65,9%), melting point 154-155oC.

An NMR spectrum (CDCl3) d 1.70 (1.5 H, c.), 1.71 (1.5 H, c.), 1.81 (1.5 H, c.), 1.84 (1.5 H, c. ), 2.05 (1.5 H, c.), 2.07 (1.5 H, c.), 2.12 (1.5 H, c.), 2.14 (1.5 H, c. ), 3.01 (1H, d, J=15.6 Hz), 3.58 (1H, c.), 3.62 (0.5 H, d, J=15.6 Hz), 3.76 (0.5 H, d, J=15.6 Hz), 6.71 (0.5 H, broad singlet), 6.74 (0.5 H, d, J= 12.0 Hz), 7.15-7.70 (3H, m), 7,89 (2H, m), 7.96 (0.5 H, d, J=12.0 Hz), 8.40 (0.5 H, d, J=1.6 Hz).

Example 84. 5-Amino-2,4,6,7-tetramethyl-2-(2-phenylethyl)-2,3 - dihydrobenzofuran.

6 N. Aqueous sodium hydroxide solution (3 ml) was added to a solution of 5-acetylamino-2,4,6,7-tetramethyl-2-(2-phenylethyl)-2,3-dihydroindole cooling the reaction mixture was diluted with water, and the resulting product was extracted with ethyl acetate. The extract was washed with water, dried and concentrated. The residue was purified by chromatography on columns of silica gel (a simple mixture of isopropyl ether and ethyl acetate, 2: 1). The crude crystals are recrystallized from hexane with the formation of the target compound (0.32 g, yield of 54.4%), melting point 45-46oC (decomposition).

An NMR spectrum (CDCl3) d 1.47 (3H, c.), 2.03 (2H, m), 2.07 (3H, c.), 2.09 (3H, c. ), 2.14 (3H, c.), 2.76 (2H, m), 2.92 (1H, d, J=15.4 Hz), 3.00 (2H, broad singlet), 3.07 (1H, d, J=15.4 Hz), 7.01-7.30 (5H, m).

Example 85. 5-Amino-2,4,6,7-tetramethyl-2-[2-(4-forfinal)ethyl]-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 54.6% ) melting point 62-63oC (hexane).

An NMR spectrum (CDCl3) d 1.47 (3H, c.), 1.98 (2H, m), 2.10 (3H, c.), 2.14 (3H, c. ), 2.19 (3H, c.), 2.72 (2H, m), 2.90 (1H, d, J=14.0 Hz), 3.00 (2H, broad singlet), 3.05 (1H, d, J=14.0 Hz), 6.95 (2H, m), 7.13 (2H, m).

Example 86. Hydrochloride methyl-3 [5-amino-2,4,6,7-tetramethyl-2,3 - dihydrobenzofuran-2-yl]acrylate.

Complex ethyl ester of 3-[5-acetylamino-2,4,6,7-tetramethyl-2,3 - dihydrobenzofuran-2-yl] acrylic acid (0.5 g, was 1.58 mmol) was dissolved in methanol (5 ml). Tim refrigerator for 1 hour. The reaction mixture was cooled and filtered the precipitated crystals. The crude crystals are recrystallized from a mixture of ethanol and simple isopropyl ether with the formation of the target compound (0.35 g, yield 74,7%), melting point 225-234oC.

An NMR spectrum (DMCO-d6) d 1.58 (3H, c.), 2.11 (3H, c.), 2.19 (3H, c.), 2.21 (3H, c. ), 3.12 (1H, d, J=15.0 Hz), 3.24 (1H, d, J=15.0 Hz), 3.65 (3H, c.), 5.93 (1H, d, J=16.0 Hz), 7.04 (1H, d, J=16.0 Hz), 9.50 (2H, broad singlet).

Example 87. Hydrochloride 5-amino-2-methyl bromide-2,4,6,7-tetramethyl-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 90.2 per cent ), melting point 235-245oC (a mixture of ethanol and isopropyl ether).

An NMR spectrum (DMCO-d6) d 1.53 (3H, c.), 2.04 (3H, c.), 2.23 (3H, c.), 2.24 (3H, c. ), 3.03 (1H, d, J=16.0 Hz), 3.27 (1H, d, J=16.0 Hz), 3.77 (2H, c.), 9.85 (2H, broad singlet).

Example 88. Hydrochloride 5-amino-2-phenylthiomethyl-2,4,6,7-tetramethyl-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 94.5%) melting point 130-131oC (a mixture of ethanol and simple isopropyl ether).

An NMR spectrum (DMCO-d6) d 1.51 (3H, c.), 1.87 (3H, c.), 2.19 (3H, c.), 2.20 (3H, c. ), 2.99 but-2-(4-forfinal)thiomethyl-2,4,6,7-tetramethyl - 2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 80.9%), melting point 204-210oC (a mixture of ethanol and simple isopropyl ether).

An NMR spectrum (DMCO-d6) d 1.49 (3H, c.), 1.84 (3H, c.), 2.19 (3H, c.), 2.20 (3H, c.), 2.98 (1H, d, J=15.8 Hz), 3.21 (1H, d, J=15.8 Hz), 3.31 (1H, d, J= 14.0 Hz), 3.39 (1H, d, J=14.0 Hz), 7.13 (2H, d J=9.0 Hz), 7.38 (2H, double doublet, J=9.0 Hz and J=5.4 Hz), 9.67 (2H, broad singlet).

Example 90. Hydrochloride 5-amino-2-(4-hydroxyphenyl)thiomethyl-2,4,6,7 - tetramethyl-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 96.2%), melting point 230-236oC (decomposition) (a mixture of ethanol and simple isopropyl ether).

An NMR spectrum (DMCO-d6) d 1.46 (3H, c.), 1.91 (3H, c.), 2.18 (6H, c.), 2.94 (1H, d, J=15.8 Hz), 3.20 (1H, d, J=15.8 Hz), 3.20 (1H, d, J=15.8 Hz), 3.20 (2H, c.), 6.70 (2H, d J=8.6 Hz), 7.19 (2H, d J=8.6 Hz), 9.45 (2H, broad singlet), 9.56 (2H, c.).

Example 91. The dihydrochloride of 5-amino-2-(1-Mei-2-yl)thiomethyl-2,4,6,7 - tetramethyl-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 65,3%), melting point 220-225oC (decomposition) (a mixture of ethanol and posts), 3.29 (1H, d, J=16.2 Hz), 3.50 (3H, c.), 3.56 (1H, d, J=14.6 Hz), 7.71 (1H, d, J=1.8 Hz), 7.75 (1H, d, J=1.8 Hz), 10.2 (2H, broad singlet).

Example 92. Hydrochloride 5-amino-2-(2-benzothiazolyl)thiomethyl-2,4,6,7 - tetramethyl-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 89.1%), melting point 204-208oC (decomposition) (a mixture of ethanol and simple isopropyl ether).

An NMR spectrum (DMCO-d6) d 1.58 (3H, c.), 1.76 (3H, c.), 2.16 (3H, c.), 2.21 (3H, c.), 3.08 (1H, d, J=15.8 Hz), 3.28 (1H, d, J=15.8 Hz), 3.79 (1H, d, J= 14.6 Hz), 3.88 (1H, d, J=14.6 Hz), 7.37 (1H, T. J=7.6 Hz), 7.47 (2H, so J= 7.6 Hz), 7.78 (1H, d, J=7.6 Hz), 8.01 (1H, d, J=7.6 Hz), 9.65 (2H, broad singlet).

Example 93. Hydrochloride 5-amino-2-benzyldimethyl-2,4,6,7-tetramethyl-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 74,1%), melting point 170-172oC (a mixture of ethanol and simple isopropyl ether).

An NMR spectrum (DMCO-d6) d 1.44 (3H, c.), 2.07 (3H, c.), 2.23 (6H, c.), 2.80 (2H, c.), 2.93 (1H, d, J=16.0 Hz), 3.13 (1H, d, J=16.0 Hz), 3.77 (1H, d, J= 13.8 Hz), 3.87 (1H, d, J=13.8 Hz), 7.29 (5H, m), 9.77 (2H, broad singlet).

Example 94. 5-Amino-2,4,6,7-tetramethyl-2-(4-pyridyl)thiomethyl]-2,3 - dihydrobenzofuran.

The specified melting point of 96-97oC (a mixture of ethyl acetate and simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.58 (3H, c.), 2.00 (3H, c.), 2.06 (3H, c.), 2.06 (3H, c.), 2.85 (2H, broad singlet), 2.98 (1H, d, J=15.6 Hz), 3.21 (1H, d, J= 15.6 Hz), 3.25 (1H, d, J=14.0 Hz), 3.32 (1H, d, J=14.0 Hz), 7.14 (2H, double doublet, J=4.8 Hz and J=2.0 Hz), 8.33 (2H, double doublet, J=4.8 Hz, J= 2.0 Hz).

Example 95. Hydrochloride 5-amino-2,4,6,7-tetramethyl-2-propylthiouracil-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 74,6%), the melting point of 186-188oC (a mixture of ethanol and simple isopropyl ether).

An NMR spectrum (DMCO-d6) d 0.97 (3H, so J=7.4 Hz), 1.40 - 1.70 (2H, m), 1.53 (3H, c.), 2.09 (3H, c.), 2.50 (6H, c.), 2.45 - 2.60 (2H, m), 2.82 (2H, c.), 2.88 (1H, d, J=15.4 Hz), 3.28 (1H, d, J=15.4 Hz), 10.10 (2H, broad singlet).

Example 96. 5-Amino-2-(2-hydroxyethyl)thiomethyl-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 32.3%) and the melting point of 108-109oC (a mixture of ethyl acetate and simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.51 (3H, c.), 2.07 (3H, c.), 2.08 (3H, c.), 2.11 (3H, c. ), 2.80 (1H, broad singlet), 2.81 (2H, so J=5.4 Hz), 2.90 (1H, d, J=15.0 Hz), 2.92 (1H, d, J=15.4 Hz), 3.19 (1H, d, J=15.4 Hz), 3.20 (2 is ylthio] propionic acid.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 77.5%), melting point 139-140oC (a mixture of ethyl acetate and simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.51 (3H, c.), 2.07 (6H, c.), 2.09 (3H, c.), 2.64 (2H, so J=6.9 Hz), 2.80 (1H, d, J=14.0 Hz), 2.87 (1H, d, J=14.0 Hz), 2.88 (2H, so J=6.8 Hz), 2.91 (1H, d, J=15.4 Hz), 3.20 (1H, d, J=15.4 Hz), 4.90 (2H, broad singlet).

Example 98. 5-Amino-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran-2-yl - phenylsulfanyl.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield 21,0%).

An NMR spectrum (CDCl3) d 1.60 (1.5 H, c.), 1.84 (1.5 H, c.), 2.04 (1.5 H, c.), 2.09 (4.5 H, c.), 2.11 (3H, c.), 2.90-3.45 (5.5 H, m), 3.69 (5.5 H, d, J=15.8 Hz), 7.48 (2H, m), 7.63 (2H, m).

Example 99. 5-Amino-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran-2-yl - phenylsulfonyl.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield of 91.7%), melting point 150-151oC (a mixture of ethyl acetate and simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.69 (3H, c.), 1.81 (3H, c.), 2.02 (3H, c.), 2.05 (3H, c.), 2.99 (1H, d, J=15.6 Hz), 3.30 (2H, broad singlet), 3.54 (3H, c. ), 3.60 (1H, d, J=15.6 Hz), 7.40-7.70 (3H, m), 7.85 (2H, m).

Example 100. Hydra is lo synthesized in accordance with methods described above (yield of 79.6% ), melting point 119-121oC (a mixture of ethanol and simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.48 (6H, c.), 2.20 (3H, c.), 2.54 (3H, c.), 3.42 (2H, c.), 8.61 (2H, broad singlet).

Example 101. The dihydrochloride of 5-amino-2,2,6,7-tetramethyl-4-dimethylamino-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 64.5% ), melting point 240-244oC (ethanol).

An NMR spectrum (DMCO-d6) d 1.42 (6H, c.), 2.02 (3H, c.), 2.18 (3H, c.), 2.63 (6H, c.), 3.17 (2H, c.), 4.94 (2H, broad singlet).

Example 102. Hydrochloride 5-amino-2,2,4,7-tetramethyl-6-dimethylamino-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 63.2% ), melting point 236-238oC (ethanol).

An NMR spectrum (DMCO-d6) d 1.41 (6H, c.), 2.10 (3H, c.), 2.19 (3H, c.), 2.72 (6H, c.), 2.96 (2H, c.), 9.66 (2H, broad singlet).

Example 103. 5-Amino-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran.

Sulfuric acid (2.0 ml) was added to a solution of 4-amino-2,3,5-trimethylphenol (2.0 g, 13,2 mmol) and 2-methyl-2-propanol (1,15 g, 15.8 mmol) in dichloromethane (20 ml) and the resulting mixture was heated under reflux in carbonate sodium and separated the organic layer. The organic layer was washed with water, dried and concentrated. The residue was purified by chromatography on columns of silica gel (simple isopropyl ether). The resulting product was recrystallized from hexane with the formation of the target compound in the form of crystals (460 mg, 16.9%), melting point 110-111oC.

An NMR spectrum (CDCl3) d 1.45 (3H, c.), 2.06 (3H, c.), 2.09 (3H, c.), 2.13 (3H, c.), 2.94 (2H, c.), 3.26 (2H, broad singlet).

Example 104. 2,2,4,6,7-Pentamethyl-5-phenylamino-2,3-dihydrobenzofuran.

To a solution of 3,5,6-trimethyl-2-(2-methyl-2-propenyl)-4-phenylalaninol (1.40 g, to 4.98 mmol) in methanol (30 ml) was added concentrated hydrochloric acid (10 ml) under ice cooling, after which the mixture was heated under reflux in an argon atmosphere. The reaction mixture was cooled, neutralize aqueous solution of sodium bicarbonate and was extracted with ethyl acetate. The extract was washed with saturated saline and concentrated. The residue was recrystallized from simple isopropyl ether with the formation of the target compound in the form of crystals (0.97 g, yield of 69.3%), melting point 148 - 150oC.

An NMR spectrum (CDCl3) d 1.49 (6H, c.), 2.04 (3H, c.), 2.10 (3H, c.), 2.12 (3H, c. ), 2.95 (2H, c.), 5.03 (1 is l-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized according to the procedure described in example 104 (exit 60,0%), melting point 106-107oC (a mixture of pentane and simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.49 (6H, c.), 2.02 (3H, c.), 2.07 (3H, c.), 2.12 (3H, c.), 2.95 (2H, c.), 5.04 (1H, broad singlet), 6.36 (2H, d, J=8.8 Hz), 7.06 (2H, d, J=8.8 Hz).

Example 106. 5-(4-Methoxybenzylamine)-2,2,4,6,7-pentamethyl-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized according to the procedure described in example 104 (exit 61,2%), melting point 117-119oC (a mixture of pentane and simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.49 (6H, c.), 2.04 (3H, c.), 2.09 (3H, c.), 2.12 (3H, c. ), 2.95 (2H, c.), 3.73 (3H, c.), 4.86 (1H, broad singlet), 6.41 (2H, d J=9.0 Hz), 6.73 (2H, d J=9.0 Hz).

Reference example 1. 4-Amino-2,3,5-trimethylphenol.

Solid Na2CO3(13,7 g, 129 mmol) slowly added under stirring at room temperature to a solution of sulfanilic acid (49,4 g, 258 mmol) in water (250 ml). After the conversion of the reaction mixture in a homogeneous solution (if the mixture did not dissolve at room temperature, it was a little heated this mixture was cooled with ice and the solution was added NaNO2(19,4 g, 280 mm what the solution was added dropwise to a mixture of concentrated hydrochloric acid (46 ml), and ice (100 g) for 10 minutes under stirring with ice cooling and maintaining the internal temperature dropping funnel below 10oC. After the addition, the reaction mixture was stirred for 30 minutes under ice cooling. Then in another reactor equipped with a mechanical stirrer, was injected water (250 ml), NaOH (56,8 g, 142 mmol) and 2,3,5-trimethylphenol (35,3 g, 259 mmol) and this mixture was added dropwise into the reaction mixture, producing a stirring in a stream of nitrogen at a temperature of from -10oC to 5oC for 15 minutes. At this time the ice bath was added the desired amount of ice to cool the reaction system and maintain the temperature of the contents in the drip funnel below 10oC. After the addition the reaction mixture was heated to 50oC and added Na2S2O4(11.9 g, 68,3 mmol). Then this mixture was heated up to 80oC and added another 5 equal parts Na2S2O4(214,2 g of 1.23 mol) at 5 minute intervals. The reaction mixture was stirred for 30 minutes at the same temperature, and then cooled. Precipitated crystals were filtered. The obtained crystals were washed with water, dried, and then recrystallized from a mixture of ethyl acetate simple isopropyl is UP>o
C.

An NMR spectrum (CDCl3) d 2.11 (6H, c.), 2.16 (3H, c.), 3.55 (3H, broad singlet), 6.42 (2H, c.).

Reference example 2. 4-Amino-2,5-dimethylphenol.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 59,7%), melting point 216-220oC (water).

An NMR spectrum (DMCO-d6d 1.94 (3H, c.), 1.97 (3H, c.), 4.06 (2H, broad singlet), 6.33 (1H, c.), 6.38 (1H, c.), 8.04 (1H, c.).

Reference example 3. 4-Amino-3,5-dimethylphenol.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 52.2%), melting point 190-191oC (water).

An NMR spectrum (DMCO-d6) d 2.01 (6H, c.), 3.90 (2H, broad singlet), 6.28 (2H, c.), 8.19 (1H, c.).

Reference example 4. 4 Formylamino-2,3,5-trimethylphenol.

4-Amino-2,3,5-trimethylphenol (100 g, 662 mmol) was dissolved in formic acid (500 ml). This mixture was heated under reflux for 36 hours. The reaction mixture was poured into water, cooled with ice. Precipitated crystals were filtered, washed with water and dried. The crude crystals are recrystallized from ethanol with the formation of the target compound in the form of crystals (85,9 g, yield of 72.5%), melting point 219-220o

Reference example 5. 4 Formylamino-3,5-dimethylphenol.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 70,3%), melting point 239oC (a mixture of dichloromethane and simple isopropyl ether).

An NMR spectrum (DMCO-d6) d 2.0 (6H, c.), 6.46 (2H, c.), 8.19 (1H, c.), 9.13 (1H, broad singlet), 9.16 (1H, c.).

Reference example 6. 1-Acetoxy-4-acetylamino-2,3,5-trimethylbenzene.

4-Amino-2,3,5-trimethylphenol (26.5 g, 17.5 mmol) was dissolved in pyridine (80 ml). To this solution under stirring was added acetic anhydride (53 ml, 56.2 mmol). After stirring the reaction mixture for 1 hour, it was poured into water, cooled with ice. Precipitated crystals were filtered, washed with water and dried. Recrystallized from ethyl acetate with the formation of the target compound (36.5 g, yield 88.5 percent ), melting point 174 - 175oC.

An NMR spectrum (CDCl3) d 2.00-2.25 (12H, m), 2.31 (3H, c.), 6.60-6.90 (2H, m).

Reference example 7. 1-Acetoxy-4-acetylamino-2,3-xylene.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 88.3%), melting point 155-156oC (a mixture of dichloromethane and simple souroti singlet), 7.37 (1H, d J=8.5 Hz).

Reference example 8. 1-Acetoxy-4-acetylamino-2,5-xylene.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 54,9%), melting point 177oC (a mixture of dichloromethane and simple isopropyl ether).

An NMR spectrum (CDCl3) d 2.12 (3H, c.), 2.16 (3H, c.), 2.30 (3H, c.), 6.81 (1H, c.), 7.02 (1H, broad singlet), 7.57 (1H, c.).

Reference example 9. 4-Acetylamino-2,3,5-trimethylbenzene.

A solution of potassium carbonate (27 g, 195 mmol) in water (150 ml) was added to a solution of 1-acetoxy-4-acetylamino-2,3,5-trimethylbenzene (66,0 g, 324 mmol) in methanol (300 ml) and the resulting mixture was stirred for 1 hour in argon atmosphere. To the reaction mixture were added 1 N. aqueous solution of hydrochloric acid with the aim of weak acidification of the mixture, after which it was diluted with water. Precipitated crystals were filtered, washed with water and dried. Recrystallized from a mixture of ethyl acetate and simple isopropyl ether with the formation of the target compounds (to 36.8 g, yield 67,9%), melting point 189-190oC (a mixture of ethyl acetate and simple isopropyl ether).

An NMR spectrum (DMCO-d6) d 1.98 (3H, c.), 1.99 (6H, c), 2.01 (3H, c.), 6.50 (1H, c.), 8.95 (1H, c.), 9.00 (1H, c.).

An NMR spectrum (CDCl3d 2.13 (3H, c.), 2.16 (3H, c.), 2.18 (3H, c.), 6.66 (1H, d J=8.5 Hz), 7.0! (1H, d J=8.5 Hz), 7.22 (1H, broad singlet), 7.29 (1H, c.).

Reference example 11. 4-Acetylamino-3,5-dimethylphenol.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 92.1%), melting point 183oC (a mixture of dichloromethane and simple isopropyl ether).

An NMR spectrum (DMCO-d6) d 1.97 (3H, c.), 2.04 (6H, c), 6.58 (1H, c.), 6.91 (1H, c.), 9.03 (2H, c.).

Reference example 12. 4 Formylamino-2,3,5-trimethyl-1-(2-methyl-2-propenyloxy)benzene.

Potassium carbonate (74,0 g, 0.54 mol) was added to a solution of 4-formylamino-2,3,5-trimethylphenol (85,5 g, 0.48 mol) and metalloid (45,3 g, 0.5 mol) in dimethylformamide (300 ml) and the resulting mixture was stirred at a temperature of 80oC for 3 hours. The reaction mixture was poured into water, cooled with ice. Precipitated crystals were filtered, washed with water and dried. The crude crystals are recrystallized from simple isopropyl ether with the formation of the target compound in the form of crystals (80,0 g, yield 71.6 per cent), the temperature has been melted down), 4.49 (1H, m), 4.11 (1H, broad singlet), 6.60 (1H, c.), 6.75 (1H, m), 7.98 (0.5 H, d, J=12.0 Hz), 8.41 (0.5 H, c.).

Reference example 13. 4-Acetylamino-2,3,5-trimethyl-1-(2-methyl-2-propenyloxy)benzene.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 92.6%), melting point 149-150oC (simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.84 and 1.86 (3H, c.), 2.14 (3H, c.), 2.16 (3H, c.), 2.19 (3 c.), 2.20 (3H, c.), 4.32 and 4.38 (2H, c.), 4.98 (1H, m), 5.11 (1H, broad singlet), 6.58 and 6.50 (1H, c.), 6.60 and 6.72 (1H, broad singlet).

Reference example 14. 2,3,5-Trimethyl-1-(2-methyl-2-propenyloxy)benzene.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 98,9%), boiling point 108-112oC (10 mm Hg).

An NMR spectrum (CDCl3) d 1.87 (3H, c.), 2.17 (3H, c.), 2.26 (3H, c.), 2.30 (3 c.), 2.42 (2H, c.), 5.00 (1H, broad singlet), 5.15 (1H, broad singlet), 6.55 (1H, broad singlet), 6.64 (1H, broad singlet).

Reference example 15. 4-Acetylamino-2,3-dimethyl-1-(2-methyl-2-propenyloxy)benzene.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 86,2%), melting point 154-156oC (a mixture of dichloromethane and simple isopr is), 6.70 (1H, d, J=8.8 Hz), 6.89 (1H, broad singlet), 7.20 (1H, d, J=8.8 Hz).

Reference example 16. 4-Acetylamino-2,5-dimethyl-1-(2-methyl-2-propenyloxy)benzene.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 84.3%), melting point 128-132oC (a mixture of dichloromethane and simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.60 (3H, c.), 1.84 (3H, c.), 2.17 (3H, c.), 2.20 (6H, c. ), 4.40 (2H, c.), 4.98 (1H, c.), 5.11 (1H, c.), 6.63 (1H, c.), 6.80 (1H, broad singlet), 7.28 (1H, c.).

Reference example 17. 4 Formylamino-3,5-dimethyl-1-(2-methyl-2-propenyloxy)benzene.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 98,4% ), melting point 128-129oC (simple isopropyl ether).

An NMR spectrum (DMCO-d6) d 1.77 (3H, c.), 2.1 (6H, c.), 4.43 (2H, c.), 4.95 (1H, c.), 5.05 (1H, c.), 6.68 (2H, c.), 8.22 (1H, c.), 9.26 (1H, c.).

Reference example 18. 4 Formylamino-3,5-dimethyl-2-(2-methyl-2-propenyl)-1-(2-methyl-2-propenyloxy)benzene.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 98,4%), melting point 109oC (a mixture of dichloromethane and simple isopropyl ether).

An NMR spectrum (DMCO-d

Reference example 19. 4 Formylamino-2,3,5-trimethyl-6-(2-methyl-2-propenyloxy)phenol.

4 Formylamino-2,3,5-trimethyl-1-(2-methyl-2-propenyloxy)benzene (80 g, 0.34 mol) was dissolved in N,N-diethylaniline (500 ml). This solution was heated at a temperature of 200oC for 3 hours. Then the solution was cooled. After deposition of crystals was added hexane. Precipitated crystals were filtered with the formation of the target compound in the form of crystals (75.2 g, yield 94,0%), the Crude crystals are recrystallized from a mixture of etelaat and simple isopropyl ester, melting point 163-164oC.

An NMR spectrum (CDCl3) d 1.80 (3H, c.), 2.16 (3H, c.), 2.17 (1.5 H, c.), 2.19 (1.5, c. ), 2.20 (1.5 H, c.), 2.21 (1.5 H, c.), 3.38 (2H, broad singlet), 4.65 (1H, m), 4.88 (1H, m), 5.16 (0.5 H, (c.), 5.19 (0.5 H, (c.), 6.70 (1H, m ), 7.95 (0.5 H, d, J=12.0 Hz), 8.42 (0.5 H, d, J=1.8 Hz).

Reference example 20. 4-Acetylamino-2,3,5-trimethyl-6-(2-methyl-2-propenyloxy)phenol.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 97.7%), melting point 209-210oC (a mixture of ethyl acetate and simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.73 (3H, c.), 1.94 (3H, c.), 1.99 (6H, c.), 2.09 (3H, c.), 3.33 (2H, m), 4.28 (1H, broad singlet), 4.64 (1H, broad singlet), 7.86 P> Specified in the title compound was synthesized in accordance with the methodology described above (yield of 80.6%), boiling point 124-126oC (10 mm Hg).

An NMR spectrum (CDCl3) d 1.79 (3H, c.), 2.14 (3H, c.), 2.24 (6H, c.), 3.37 (2H, c.), 4.74 (1H, m), 4.88 (1H, m), 5.08 (1H, c.), 6.63 (1H, c.).

Reference example 22. 4-Acetylamino-2,3-dimethyl-6-(2-methyl-2-propenyl)phenol.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 91.8%), melting point 149-151oC (a mixture of dichloromethane and simple isopropyl ether).

An NMR spectrum (CDCl3d 1.72 (3H, c.), 2.12 (3H, c.), 2.16 (3H, c.), 2.17 (3H, c.), 3.32 (2H, c.), 4.89-4.94 (2H, m), 5.39 (1H, c.), 6.92 (1H, broad singlet), 7.00 (1H, c.).

Reference example 23. 4-Acetylamino-2,5-dimethyl-6-(2-methyl-2-propenyl)phenol.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 98.7 per cent), melting point 183-185oC (a mixture of dichloromethane and simple isopropyl ether).

An NMR spectrum (CDCl3) d 1.79 (3H, c.), 2.11-2.22 (9H, m), 3.38 (2H, c.), 4.60 (1H, c.), 4.83 (1H, c.), 7.11 (1H, c.).

Reference example 24. 4 Formylamino-3,5-dimethyl-2-(2-methyl-2-propenyl)phenol.

Specified in the title compound was synthesized in embedded ether).

An NMR spectrum (DMCO-d6) d 1.71 (3H, c.), 1.97 (3H, c.), 2.04 (3H, c.), 3.25 (2H, c. ), 4.33 (1H, c.), 4.65 (1H, c.), 6.55 (1H, c.), 8.19 (1H, c.), 9.09 (1H, c.).

Reference example 25. 2,6-Bis-(2-methyl-2-propenyl)-4-formylamino-3,5-dimethylphenol.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 84,2%), melting point 169-170oC (simple isopropyl ether).

An NMR spectrum (DMCO-d6d 1.72 (6H, c.), 1.98 (6H, c.), 3.33 (4H, c.), 4.28 (2H, c.), 4.65 (2H, c.), 7.86 (1H, c.), 8.20 (1H, c.), 9.19 (1H, c.).

Reference example 26. 2-Bromo-3,5,6-trimethylamino.

A solution of tert-butylamine (73 g, 1.0 mol) in toluene (1 l) was cooled to a temperature of from -20oC to 30oC for 10 minutes was added dropwise bromine (79,9 g, 0.5 mol). The reaction mixture was cooled to a temperature of from -70oC to -75oC and to this mixture was added dropwise 2,3,5-trimethylphenol (68 g, 0.5 mol), which was pre-dissolved in minimum amount of dichloromethane. The reaction mixture was stirred at the same temperature for 30 minutes and then at room temperature for 3 hours. Then the mixture was washed with water, dried and concentrated. Sodium hydride (60% content, 22 g, 0.55 mol) were placed in another reactor, and 2 or 3 times washed with hexane, n is asanoha product in dimethylformamide (50 ml). The reaction mixture was stirred for 30 minutes and was added dropwise logmean (34,2 ml, 0.55 mol). The resulting mixture was diluted with water and the resulting product was extracted with simple isopropyl ether. The extract was washed with water, dried, and then concentrated. The concentrated residue was distilled under reduced pressure. Collected fraction with a boiling point of from 130 to 130oC, resulting in the target connection (32,3 g, yield of 28.6%).

An NMR spectrum (CDCl3d 2.220(3H, c.), 2.21 (3H, c.), 2.34 (3H, c.), 3.76 (3H, c.), 6.83 (1H, c.).

Reference example 27. 1-(2-Methoxy-3,4,6-trimetilfenil)-1-phenyl-2-methylpropanol.

A solution of 2-bromo-3,5,6-trimethylamine (3.0 g, of 13.1 mmol) in tetrahydrofuran (20 ml) was cooled to -78oC and was added dropwise n-utility (1.6 M solution in hexane, 8.2 ml of 13.1 mmol). The reaction mixture was stirred at the same temperature for 15 minutes. Then was added dropwise a solution of isobutylbenzene (1,94 g of 13.1 mmol) in tetrahydrofuran (5 ml) and the resulting mixture was stirred at room temperature for 30 minutes. The reaction mixture was diluted with water and the resulting product was extracted with simple isopropyl ether. The extract was washed with water, dried, and then the oxygen is and melting 80-81oC.

An NMR spectrum (CDCl3) d 0.88 (3H, d, J=6.6 Hz), 1.05 (3H, d, J=6.4 Hz), 2.07 (3H, c.), 2.18 (3H, c.), 2.58 (3H, c.), 2.82 (1H, four-Quartet, J= 6.6 Hz and J=6.4 Hz), 2.90 (3H, c.), 6.18 (1H, broad singlet), 6.75 (1H, c. ), 7.10-7.30 (3H, m), 7.40 - 7.50 (2H, m).

Reference example 28. 1-(4-Forfinal)-1-(2-methoxy)-3,4,6-trimetilfenil)-2-methylpropanol.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 97,9%), melting point 102-103oC (hexane).

An NMR spectrum (CDCl3) d 0.88 (3H, d, J=6.6 Hz), 1.02 (3H, d, J=6.4 Hz), 2.08 (3H, c.), 2.19 (3H, c.), 2.53 (3H, c.), 2.80 (1H, four-Quartet, J= 6.6 Hz and J=6.4 Hz), 6.23 (1H, broad singlet), 6.75 (1H, c.), 6.95 (2H, so J=8.8 Hz), 7.40 (2H, double doublet, J=8.8 Hz and J=5.4 Hz).

Reference example 29. 1-(2-Methoxy-3,4,6-trimetilfenil)-1-(4-were)-2 - methylpropanol.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 80.6%), melting point 103-104oC (hexane).

An NMR spectrum (CDCl3) d 0.89 (3H, d, J=6.6 Hz), 1.03 (3H, d, J=6.4 Hz), 2.09 (3H, c.), 2.19 (3H, c.), 2.30 (3H, c.), 2.56 (3H, c.), 2.82 (1H, four-Quartet, J=6.6 Hz and J=6.4 Hz), 2.95 (3H, c.), 6.18 (1H, broad singlet), 6.75 (1H, c.), 7.07 (2H, d J=8.2 Hz), 7.32 (2H, d J=8.2 Hz).

Reference example 30. 1-(2-Methoxy-3,4,6-trimetilfenil)-1-(4-propertyKey, described above (yield 74,6% ), the melting point of 59-60oC (hexane).

An NMR spectrum (CDCl3) d 0.87 (3H, so J=6.4 Hz), 0.90 (3H, d, J=6.6 Hz), 1.03 (3H, d, J=6.4 Hz), 1.60 (2H, sextet, 6.4 Hz), 2.08 (3H, c.), 2.18 (3H, c. ), 2.54 (2H, so J=6.4 Hz), 2.56 (3H, c.), 2.84 (1H, four-Quartet, J= 6.6 Hz and J=6.4 Hz), 2.93 (3H, c.), 6.15 (1H, broad singlet), 7.06 (2H, d J=8.4 Hz), 7.33 (2H, d J=8.4 Hz).

Reference example 31. 1-(2-Methoxy-3,4,6-trimetilfenil)-1-(4-pentylphenol)-2 - methylpropanol.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 75,4% ), melting point 55-56oC (hexane).

An NMR spectrum (CDCl3) d 0.85 (3H, so J=6.2 Hz), 0.90 (3H, d, J=6.6 Hz), 1.03 (3H, d, J=6.6 Hz), 1.28 (4H, m), 1.56 (2H, quintet, 6.8 Hz), 2.08 (3H, c.), 2.18 (3H, c.), 2.54 (2H, so J=6.8 Hz), 2.55 (3H, c.), 2.84 (1H, septet, J= 6.6 Hz), 6.6 Hz), 2.92 (3H, c.), 6.15 (1H, broad singlet), 6.75 (1H, c. ), 7.07 (2H, d J=8.0 Hz), 7.34 (2H, d J=8.0 Hz).

Reference example 32. 1-(4-Isopropylphenyl)-1-(2-methoxy-3,4,6-trimetilfenil)-2-methylpropanol.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (the output of 65.1%).

An NMR spectrum (CDCl3) d 0.91 (3H, d, J=6.6 Hz), 1.02 (3H, d, J=6.6 Hz), 1.20 (6H, d, J=7.0 Hz), 2.08 (3H, c.), 2.08 (3H, c.), 2.17 (3H, c.), 2.54 (3H, c. ), 2.84 (1H, septet, J=6.6 Hz), 2.93 (3H, c.), 2.96 (1H, septet, J= 6.63,4,6-trimetilfenil)-1-(3-pyridyl)-2-methylpropanol.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield 68,9%).

An NMR spectrum (CDCl3) d 0.93 (3H, d, J=6.6 Hz), 1.03 (3H, d, J=6.6 Hz), 2.09 (3H, c.), 2.09 (3H, c.), 2.19 (3H, c.), 2.51 (3H, c.), 2.90 (1H, septet, J= 6.6 Hz), 3.05 (3H, c.), 6.29 (1H, broad singlet), 6.76 (1H, c.), 7.22 (1H, double doublet, J=4.8 Hz and J=8.0 Hz), 7.79 (1H, double triplet, J= 2.0 Hz and J=8.0 Hz), 8.43 (1H, double doublet, J=2.0 Hz and J=4.8 Hz), 8.70 (1H, d, J=2.0 Hz).

Reference example 34. 1-(2-Methoxy-3,4,6-trimethyl)-1-(4-dimethylaminophenyl)-2-methylpropanol.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 59,1% ), melting point 95-97oC (hexane).

An NMR spectrum (CDCl3) d 0.93 (3H, d, J=6.6 Hz), 1.00 (3H, d, J=6.4 Hz), 2.08 (3H, c.), 2.18 (3H, c.), 2.53 (3H, c.), 2.82 (1H, four-Quartet, J= 6.6 Hz and J=6.4 Hz), 2.90 (6H, c.), 2.99 (3H, c.), 6.12 (1H, broad singlet), 6.66 (2H, d J=9.0 Hz), 7.28 (2H, d J=9.0 Hz).

Reference example 35. 3-(2-Methoxy-3,4,6-trimetilfenil)-2,4-dimethylpentan-3-ol.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield of 11.6%).

An NMR spectrum (CDCl3) d 0.78 (6H, d, J=6.6 Hz), 1.03 (6H, d, J=6.6 Hz), 2.15 (3H, c. ), 2.19 (3H, c.), 2.42 (3H, c.), 2.45 (2H, septet, J=6.6 Hz), 3.73 (3H, c.), 6.75 (Specified in the title compound was synthesized in accordance with methods described in example 3 (yield 71,9%), melting point 203oC (ethanol).

An NMR spectrum (CDCl3) d 1.45 (6H, c.), 2.10 (3H, c.), 2.11 (3H, c.), 2.17 (3H, c.), 2.98 (2H, c.), 7.00 (1H, c.), 7.33 (1H, broad singlet).

Reference example 37. 5-Acetylamino-2,2,4,7-tetramethyl-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 67,3%), melting point 161-162oC (simple isopropyl ether). An NMR spectrum (CDCl3) d 1.47 (6H, c.), 2.06 (3H, c. ), 2.13 (3H, c.), 2.14 (3H, c.), 2.93 (2H, c.), 6.81 (1H, broad singlet), 6.95 (1H, c.).

Reference example 38. Hydrochloride 5-amino-2,2,4,7-tetramethyl-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 43,0%), melting point 215-217oC (ISO-propanol).

An NMR spectrum (DMCO-d6) d 1.40 (6H, c.), 2.22 (3H, c.), 2.29 (3H, c.), 2.94 (2H, c.), 6.49 (1H, c.), 9.58 (2H, broad singlet).

Reference example 39. Hydrochloride 5-amino-2,2,6,7-tetramethyl-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield of 38.7%), melting point 235-238oC (ethanol).

An NMR spectrum (CDCl3) d 1.45 is l-3-phenyl-2,3-dihydrobenzofuran.

1-(2-Methoxy-3,4,6-trimetilfenil)-1-phenyl-2-methylpropanol (3.1 g, 10.4 mmol) suspended in 48% Hydrobromic acid (20 ml). This suspension was heated under reflux for 18 hours. The resulting product was extracted with simple isopropyl ether, washed with water, dried, and then concentrated. The residue was led from ethanol with the formation of the target compound (2,43 g, yield of 87.8%), melting point 86-87oC.

An NMR spectrum (CDCl3) d 1.02 (3H, c.), 1.51 (3H, c.), 1.84 (3H, c.), 2.15 (3H, c.), 2.24 (3H, c.), 4.13 (1H, c.), 6.49 (1H, c.), 6.70-7.40 (5H, m).

Reference example 41. 3-(4-Forfinal)-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 83,5%), melting point 109-110oC (methanol).

An NMR spectrum (CDCl3) d 1.02 (3H, c.), 1.49 (3H, c.), 1.83 (3H, c.), 2.14 (3H, c.), 2.24 (3H, c.), 4.10 (1H, c.), 6.49 (1H, c.), 6.60-7.20 (4H, m).

Reference example 42. 2,2,4,6,7-Pentamethyl-3-(4-were)-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 87,7%), melting point 117-118oC (methanol).

An NMR spectrum (CDCl3) d 1.02 (3H, c.), 1.50 (3H, c.), 1.85 (3H-propylphenyl)-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 84,9% ), melting point 69-70oC (methanol).

An NMR spectrum (CDCl3) d 0.90 (3H, so J=7.2 Hz), 1.02 (3H, c.), 1.50 (3H, c. ), 1.61 (2H, sextet, J=8.0 Hz), 1.84 (3H, c.), 2.15 (3H, c.), 2.24 (3H, c. ), 2.55 (2H, so J=8.0 Hz), 4.10 (1H, c.), 6.49 (1H, c.), 6.60-7.20 (4H, m).

Reference example 44. 2,2,4,6,7-Pentamethyl-3-(4-pentylphenol)-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield 70.7 percent).

An NMR spectrum (CDCl3) d 0.88 (3H, so J=4.6 Hz), 1.03 (3H, c.), 1.30 (4H, m ), 1.50 (3H, c.), 1.56 (2H, m), 1.85 (3H, c.), 2.15 (3H, c.), 2.24 (3H, c. ), 2.56 (2H, so J=8.0 Hz), 4.10 (1H, c.), 6.45 (1H, c.), 6.60-7.20 (4H, m).

Reference example 45. 3-(4-Isopropylphenyl)-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (the output of 65.1%).

An NMR spectrum (CDCl3) d 1.02 (3H, c.), 1.21 (6H, d, J=7.0 Hz), 1.49 (4H, m ), 1.84 (3H, c.), 2.14 (3H, c.), 2.24 (3H, c.), 2.95 (1H, septet, J=7.0 Hz), 4.09 (1H, c.), 6.48 (1H, c.), 6.70-7.20 (4H, m).

Reference example 46. 2,2,4,6,7-Pentamethyl-3-(3-pyridyl)-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in the form of c.), 2.14 (3H, c.), 2.24 (3H, c. ), 4.14 (1H, c.), 6.50 (1H, c.), 7.18 (1H, m), 8.35 (1H, m), 8.48 (1H, T. J=3.2 Hz).

Reference example 47. 2,2,4,6,7-Pentamethyl-3-(4-dimethylaminophenyl)-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 88.1 percent ), melting point 124-125oC (methanol).

An NMR spectrum (CDCl3) d 1.03 (3H, c.), 1.48 (3H, c.), 1.85 (3H, c.), 2.14 (3H, c. ), 2.23 (3H, c. ), 2.91 (6H, c.), 4.04 (1H, c.), 6.47 (1H, c.), 6.55-7.00 (4H, m).

Reference example 48. 3-(4-Isopropyl)-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield 88.1 per cent).

An NMR spectrum (CDCl3) d 0.73 (3H, d, J=6.8 Hz), 0.98 (3H, d, J=7.2 Hz), 1.21 (3H, c.), 1.57 (3H, c.), 2.06 (3H, c.), 2.10 (1H, m), 2.22 (3H, c.), 2.73 (1H, d, J=2.8 Hz), 6.49 (1H, c.).

Reference example 49. 2,2,4,6,7-Pentamethyl-7-nitro-2,3-dihydrobenzofuran.

Cooled mixed solution of acetic anhydride (5 ml) and acetic acid (5 ml) and stirring was carefully added nitric acid (5 ml). Then was added dropwise a solution of 2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran (2.9 g, a 13.9 mmol) in acetic anhydride (5 ml), after which the mixture was stirred for 30 minutes. The reaction mixture is in the saturated solution of sodium bicarbonate, was dried and concentrated. The residue was purified by chromatography on columns of silica gel (a mixture of hexane and simple isopropyl ether, 9:1) and was led from methanol with the formation of the target compound (0.35 g, yield 9.8%), melting point 100 - 101oC.

An NMR spectrum (CDCl3) d 1.51 (6H, c.), 2.14 (3H, c.), 2.17 (3H, c.), 2.24 (3H, c.), 2.99 (2H, c.).

Reference example 50. 2,2,4,6,7-Pentamethyl-5-nitro-3-phenyl-2,3-dihydrobenzofuran.

Cooled mixed solution of acetic anhydride (3 ml) and acetic acid (3 ml) and stirring was carefully added nitric acid (3 ml). Then was added dropwise a solution of 2,2,4,6,7-pentamethyl-3-phenyl-2,3 - dihydrobenzofuran (3.7 g, a 13.9 mmol) in acetic anhydride (3 ml), after which the mixture was stirred for 30 minutes. The reaction mixture was poured into water, cooled with ice, and the resulting product was extracted with ethyl acetate. The extract was washed with saturated sodium bicarbonate solution, dried and concentrated. The residue was purified by chromatography on columns of silica gel (a mixture of hexane and simple isopropyl ether, 9:1) and was led from methanol with the formation of the target compound (2,08 g, yield 48,1%), melting point 155-156oC.

the hydrated example 51. 3-(4-Forfinal)-2,2,4,6,7-pentamethyl-5-nitro-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 66,3% ), melting point 94-95oC (methanol).

An NMR spectrum (CDCl3) d 1.04 (3H, c.), 1.50 (3H, c.), 1.84 (3H, c.), 2.18 (3H, c.), 2.20 (3H, c.), 4.14 (1H, c.), 6.85 - 7.20 (4H, m).

Reference example 52. 2,2,4,6,7-Pentamethyl-3-(4-were)-5-nitro-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield 56%).

An NMR spectrum (CDCl3) d 1.05 (3H, c.), 1.50 (3H, c.), 1.84 (3H, c.), 2.18 (3H, c.), 2.20 (3H, c.), 2.32 (3H, c.), 4.11 (1H, c.), 6.50-7.20 (4H, m).

Reference example 53. 2,2,4,6,7-Pentamethyl-3-(4-propylphenyl)-5-nitro-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield 65.8 per cent).

An NMR spectrum (CDCl3) d 0.91 (3H, so J=7.4 Hz), 1.04 (3H, c.), 1.50 (3H, c. ), 1.61 (2H, sextet, J=7.4 Hz), 1.84 (3H, c.), 2.18 (3H, c.), 2.20 (3H, c. ), 2.55 (2H, so J=7.4 Hz), 4.12 (1H, c.), 6.50-7.20 (4H, m).

Reference example 54. 2,2,4,6,7-Pentamethyl-3-(4-pentylphenol)-5-nitro-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in the form of oil.30 (4H, m ), 1.50 (3H, c.), 1.59 (2H, m), 1.84 (3H, c.), 2.18 (3H, c.), 2.20 (3H, c. ), 2.56 (2H, so J=7.8 Hz), 4.11 (1H, c.), 5.50-7.20 (4H, m).

Reference example 55. 3-(4-Isopropylphenyl)-2,2,4,6,7-pentamethyl-5-nitro-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in accordance with the methodology described above (yield 48% ), melting point 109-110oC (methanol).

An NMR spectrum (CDCl3) d 1.04 (3H, c.), 1.22 (6H, d, J=6.8 Hz), 1.50 (3H, c. ), 1.84 (3H, c.), 2.18 (3H, c.), 2.20 (3H, c.), 2.87 (1H, septet, J=6.8 Hz), 4.12 (1H, c.), 6.60-7.20 (4H, m).

Reference example 56. 2,2,4,6,7-Pentamethyl-3-(3-pyridyl)-5-nitro-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield 60.7 per cent).

An NMR spectrum (CDCl3) d 1.07 (3H, c.), 1.54 (3H, c.), 1.84 (3H, c.), 2.19 (3H, c.), 2.21 (3H, c.), 4.18 (1H, c.), 7.05 - 7.35 (4H, m), 8.25-8.60 (2H, m).

Reference example 57. 2,2,4,6,7-Pentamethyl-3-(4-dimethylamino-3-nitrophenyl)-5-nitro - 2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield 24,2%).

An NMR spectrum (CDCl3) d 1.13 (3H, c.), 1.51 (3H, c.), 1.91 (3H, c.), 2.19 (3H, c.), 2.21 (3H, c.), 2.81 (6H, c.), 4.12 (1H, c.), 7.00-7.80 (4H, m).

Reference example 58. 3-Isopropyl-2,2,4,6,7-p is e oil in accordance with the methodology described above (yield 62%).

An NMR spectrum (CDCl3) d 0.72 (3H, d, J=7.0 Hz), 0.98 (3H, d, J=7.2 Hz), 1.23 (3H, c. ), 1.59 (3H, c.), 2.09 (1H, m), 2.10 (3H, c.), 2.16 (3H, c.), 2.21 (3H, c.), 2.78 (1H, d, J=2.8 Hz).

Reference example 59. 2,4,6,7-Tetramethyl-2-piperidinomethyl-5-nitro-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield of 62.8%).

An NMR spectrum (CDCl3) d 1.30-1.60 (6H, m), 1.42 (3H, c.), 2.08 (3H, c.), 2.14 (6H, c.), 2.50 (6H, m), 2.78 (1H, d, J=15.6 Hz), 3.18 (1H, d, J=15.6 Hz).

Reference example 60. 2,4,6,7-Tetramethyl-2-morpholinomethyl-5-nitro-2,3 - dihydrobenzofuran.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield 59%).

An NMR spectrum (CDCl3) d 1.44 (3H, c.), 2.07 (3H, c.), 2.15 (6H, c.), 2.57 (6H, m), 2.80 (1H, d, J=15.6 Hz), 3.21 (1H, d, J=15.6 Hz), 3.66 (4H, so J= 4.4 Hz).

Reference example 61. 2,4,6,7-Tetramethyl-2-[2-(dimethylamino)ethyl]-5-nitro-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield 53%).

An NMR spectrum (CDCl3) d 1.44 (3H, c.), 1.62 (2H, m), 2.10 (3H, c.), 2.13 (3H, c. ), 2.15 (3H, c.), 2.24 (6H, c.), 2.40 (2H, m), 2.87 (1H, d, J=15.6 Hz), 3.06 (1H, d, J=15.6 Hz).

the title compound was synthesized in accordance with methods described above (yield 46,3%), melting point 247-250oC.

An NMR spectrum (CDCl3) d 1.50 (3H, c.), 1.90 (2H, m), 2.08 (3H, c.), 2.13 (3H, c. ), 2.14 (3H, c.), 2.18 (4H, m), 2.40 (2H, m), 2.64 (2H, m), 2.97 (1H, d, J=15.6 Hz), 3.07 (2H, m), 3.17 (1H, d, J=15.6 Hz), 3.55 (2H, m).

Reference example 63. 2,2,4,6,7-Pentamethyl-2,3-dihydrobenzofuran.

3,4,5-Trimethylphenol (5.0 g, to 36.7 mmol) and 2-methyl-2-propanol (3.2 g, 44 mmol) was added to formic acid (50 ml). This mixture was heated under reflux for 3 hours. The reaction mixture was diluted simple isopropyl ether, washed with water and saturated sodium bicarbonate solution, dried and concentrated. The residue was purified by chromatography on columns of silica gel (a mixture of hexane and simple isopropyl ether 97:3) with the formation of the target compound (2.9 g, yield of 41.5%), in the form of butter.

An NMR spectrum (CDCl3) d 1.45 (3H, c.), 2.09 (3H, c.), 2.14 (3H, c.), 2.23 (3H, c.), 2.93 (2H, c.), 6.44 (1H, c.).

Reference example 64. 5-Bromo-2-methyl bromide-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized according to the procedure described in example 29 (exit 67,7%), melting point 60-61oC (methanol).

An NMR spectrum (CDCl3) d 1.61 (3H, c.), 2.15 (3H, c.), 2.27 (3H, c.), 2.35 hydrobenzoin.

Trimethylamine (5.0 ml, about 35.6 mmol) was added to a solution of 5-bromo-2-methyl bromide-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran (12.4 g, a 35.6 mmol) in ethanol (100 ml). The reaction of the decomposition-based catalytic hydrogenolysis was carried out in the presence of 5% palladium charcoal in an atmosphere of hydrogen. After the reaction the catalyst was filtered, and the filtrate was concentrated. The residue was dissolved in simple isopropyl ether, washed with water, dried and put away the solvent. The residue was led from methanol with the formation of the target compound (8,84 g, yield of 92.2%), melting point 39-40oC.

An NMR spectrum (CDCl3) d 1.63 (3H, c.), 2.08 (3H, c.), 2.17 (3H, c.), 2.21 (3H, c.), 2.92 (1H, d, J=15.8 Hz), 3.26 (1H, d, J=15.8 Hz), 2.48 (1H, d, J= 15.6 Hz), 3.58 (1H, d, J=15.6 Hz), 6.53 (1H, c.).

Reference example 66. 2,4,6,7-Tetramethyl-2-piperidinomethyl-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in the form of oil in accordance with the procedure described in example 57 (exit 81,6%).

An NMR spectrum (CDCl3) d 1.30-1.60 (6H, m), 1.44 (3H, c.), 2.05 (3H, c.), 2.15 (3H, c.), 2.19 (3H, c.), 2.40-2.65 (6H, m), 2.76 (1H, d, J=15.2 Hz), 3.06 (1H, d, J=15.2 Hz), 6.47 (1H, c.).

Reference example 67. 2,4,6,7-Tetramethyl-2-morpholinomethyl-2,3-dihydrobenzofuran.

Specified in the header connect the NMR (CDCl3) d 1.44 (3H, c.), 2.04 (3H, c.), 2.15 (3H, c.), 2.19 (3H, c. ), 2.40-2.70 (6H, m), 2.79 (1H, d, J=15.4 Hz), 3.08 (1H, d, J=15.4 Hz), 3.67 (1H, T. J=4.6 Hz), 6.48 (1H, c.).

Reference example 68. 2-Cyanomethyl-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran.

2-methyl bromide-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran (6.5 g, to 18.6 mmol) was dissolved in dimethyl sulfoxide (30 ml). Was added sodium cyanide (1,43 g, 88 mmol) and the resulting mixture was stirred at a temperature of 80oC for 18 hours. The reaction mixture was diluted with water and the resulting product was extracted with ethyl acetate. The extract was washed with water, dried and concentrated. The residue was purified by chromatography on columns of silica gel (a mixture of hexane and simple isopropyl ether, 2:1) with the formation of the target compound (4.1 g, yield 79,7%), melting point 58 - 59oC.

An NMR spectrum (CDCl3d 1.66 (3H, c.), 2.07 (3H, c.), 2.16 (3H, c.), 2.20 (3H, c.), 2.68 (1H, d, J=10.8 Hz), 2.75 (1H, d, J=10.8 Hz), 3.01 (1H, d, J= 15.8 Hz), 3.12 (1H, d, J=15.8 Hz), 6.54 (1H, c.).

Reference example 69. 2,4,6,7-Tetramethyl-2,3-dihydrobenzofuran-2-yl-acetic acid.

A solution of sodium hydroxide (12.0 g, 300 mmol) in water (30 ml) was added to a solution of 2-cyanomethyl-2,4,6,7-tetramethyl-2,3 - dihydrobenzofuran (6,9 g, 32.1 mmol) in methanol (30 ml) and the resulting mixture was heated with Obi acid and the resulting product was extracted with ethyl acetate. The extract was washed with water, dried and concentrated. The residue was led from a mixture of ethylacetate and hexane with the formation of the target compound (6.0 g, yield 79,9%), melting point 139-140oC.

An NMR spectrum (CDCl3) d 1.61 (3H, c.), 2.07 (3H, c.), 2.16 (3H, c.), 2.21 (3H, c.), 2.78 (1H, d, J=10.8 Hz), 2.85 (1H, d, J=10.8 Hz), 2.97 (1H, d, J= 15.4 Hz), 3.21 (1H, d, J=15.4 Hz), 6.52 (1H, c.), 8.50 (1H, broad singlet).

Reference example 70. N,N-Dimethyl-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran-2-yl-ndimethylacetamide.

To a solution of 2,4,6,7-tetramethyl-2,3-dihydrobenzofuran-2-yl-acetic acid (3.0 g, 12.8 mmol) in dimethylformamide (30 ml) was added monohydrate, 1-hydroxy-1H-benzotriazole (HOBt) (2.1 g, 14.1 mmol) and the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (WSC) (3.7 g, 19.2 mmol). This mixture was stirred at room temperature for 1 hour. Then was added a 50% aqueous solution of dimethylamine (3 ml) and the resulting mixture was stirred for another 30 minutes. The reaction mixture was diluted with water and the resulting product was extracted with ethyl acetate. The extract was washed with water, dried and concentrated. The residue was purified by chromatography on columns of silica gel (simple isopropyl ether) with the formation of the target compound (3.1 g, yield of 92.6%) as oil.

Reference example 71. (2,4,6,7-Tetramethyl-2,3-dihydrobenzofuran-2-yl)-acetyl-1-piperidine.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (yield 90.7 percent).

An NMR spectrum (CDCl3) d 1.55 (3H, c.), 1.60 (6H, m), 2.06 (3H, c.), 2.13 (3H, c. ), 2.19 (3H, c.), 2.78 (1H, d, J=14.8 Hz), 2.97 (1H, d, J=15.8 Hz), 2.94 (1H, d, J=14.8 Hz), 2.97 (1H, d, J=15.8 Hz), 3.24 (1H, d, J=15.8 Hz), 3.40-3.60 (4H, m), 6.50 (1H, c.).

Reference example 72. 2,4,6,7-Tetramethyl-2-[2-(dimethylamino)-ethyl]-2,3 - dihydrobenzofuran.

N,N-Dimethyl-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran-2-yl-ndimethylacetamide (3.1 g, to 11.9 mmol) was dissolved in tetrahydrofuran (50 ml), and then cooling slowly added alumoweld lithium (0.45 g). The reaction mixture was stirred at room temperature for 30 minutes and then poured into water, cooled with ice. The resulting product was extracted with ethyl acetate. The extract was washed with water, dried and concentrated. The residue was purified by chromatography on columns of silica gel (a mixture of chloroform and methanol, 95:5) with the formation of the target compound (2.2 g, yield of 81.6%) as oil.

An NMR spectrum (CDCl3) d 1.42 (3H, c.), 1.90 (2H, m), 2.06 (3H, c.), 2.12 (3H, c. ), 2.19 (3H, c.), 2.23 (6H, c.), 2.40 who yl)-2,3-dihydrobenzofuran.

Specified in the title compound was synthesized in the form of oil in accordance with the methodology described above (the output of 74.9%).

An NMR spectrum (CDCl3) d 1.42 (3H, c.), 1.30-1.60 (6H, m), 1.90 (2H, m), 2.05 (3H, c.), 2.12 (3H, c.), 2.21 (3H, c.), 2.40-2.60 (6H, m), 2.82 (1H, d, J=15.8 Hz), 3.00 (1H, d, J=15.8 Hz), 6.47 (1H, c.).

Reference example 74. 4-(4-Chlorpheniramine)-3,5,6-trimethyl-2-(2-methyl-2-propenyl)-2,5 - cyclohexadiene-1-it.

The titanium tetrachloride (2,42 ml, 22,1 mmol) was added dropwise to a solution of pyridine (7,13 ml, 88,2 mmol) in 1,2-dichloroethane 3 (40 ml) and after adding the reaction mixture was heated under reflux for 20 minutes in an argon atmosphere. After cooling the reaction mixture to it was added a solution of 3,5,6-trimethyl - 2-(2-methyl-2-propenyl)-1,4-benzoquinone (3.0 g, 14.7 mmol) and PERCHLORYL (5,62 g of 44.1 mmol) in 1,2-dichloroethane (20 ml), after which this mixture was stirred in argon atmosphere at a temperature of 90oC for 45 minutes. The reaction mixture was cooled and filtered through zerit, and the filtrate was washed with saturated saline solution, dried and concentrated. The residue was purified by chromatography on columns of silica gel (a mixture of hexane and ethyl acetate 93:7) with the formation of the target compound (4,43 g, yield 96,0%) as oil.

Specified in the title compound was synthesized in the form of oil in accordance with the method described in reference example 74, (output of 19.1%).

An NMR spectrum d 1.50-1.60 (3H, m), 1.77 (3H, broad singlet), 1.95-2.03 (3H, m ), 2.25 (3H, broad singlet), 3.16-3.25 (2H, m), 3.82 (3H, c.), 4.46-4.58 (1H, m), 4.74 (1H, broad singlet), 6.72 (2H, d J=9.0 Hz), 6.88 (2H, d J=9.0 Hz).

Reference example 76. 4-(4-Chlorpheniramine)-3,5,6-trimethyl-2-(2-methyl-2-propenyl)phenol.

To a solution of 4-(4-chlorpheniramine)-3,5,6-trimethyl-2-(2-methyl-2-propenyl)-2,5-cyclohexadiene-1-she (and 4.40 g, 14.0 mmol) in tetrahydrofuran (20 ml) was added Hydrosulphite solution of sodium (24.4 g, 0.14 mol) in water (50 ml) and the resulting mixture was stirred at room temperature for 30 minutes. After separation of the organic phase the aqueous phase was extracted with ethyl acetate and the extract was combined with the organic phase. This mixture was washed with water, dried and concentrated. The residue was purified by chromatography on columns of silica gel (a mixture of hexane and ethyl acetate, 95:5) with the formation of the target compound (4,30 g, yield 97,2%) as oil.

An NMR spectrum (CDCl3) d 1.80 (3H, c.), 2.11 (3H, c.), 2.12 (3H, c.), 2.19 (3H, c. ), 3.40 (2H, c.), 4.68 (1H, c.), Difenilamina)-3,5,6-trimethyl-2-(2-methyl-2-propenyl)phenol.

Specified in the title compound was synthesized in the form of oil in accordance with the method described in reference example 74, (yield of 98.2%).

An NMR spectrum (CDCl3) d 1.80 (3H, c.), 2.14 (6H, c.), 2.19 (3H, c.), 3.40 (2H, c.), 3.73 (3H, c.), 4.69 (1H, c.), 4.85 - 5.05 (3H, m), 6.38 (2H, d, J= 8.8 Hz), 6.73 (2H, d, J=8.8 Hz).

Reference example 78. 4 Phenylamino-3,5,6-trimethyl-2-(2-methyl-2-propenyl)phenol.

The titanium tetrachloride (2,58 ml of 23.4 mmol) was added dropwise to a solution of pyridine (7,60 ml, 93,6 mmol) in 1,2-dichloroethane (40 ml) and after adding the reaction mixture was heated under reflux for 30 minutes in an argon atmosphere. After cooling the reaction mixture to it was added a solution of 3,5,6-trimethyl - 2-(2-methyl-2-propenyl)-1,4-benzoquinone (2,40 g, 11.7 mmol) and aniline (3,35 ml of 35.1 mmol) in 1,2-dichloroethane (5 ml), after which this mixture was stirred in argon atmosphere at a temperature of 90oC for 2 hours. The reaction mixture was cooled and filtered through zerit, and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on columns of silica gel (a mixture of hexane and ethyl acetate, 98:2). The compound obtained was dissolved in tetrahydrofuran (10 ml) and to this solution was added Hydrosulphite solution n the population of the organic phase the aqueous phase was extracted with ethyl acetate and the extract was combined with the organic phase. This mixture was washed with water, dried and the solvent is kept at reduced pressure. The residue was purified by chromatography on columns of silica gel (a mixture of hexane and ethyl acetate, 95: 5) with the formation of the target compound (1,41 g, yield of 42.8%) in the form of butter.

An NMR spectrum (CDCl3) d 1.80 (3H, c.), 2.14 (6H, c.), 2.19 (3H, c.), 3.41 (2H, c. ), 3.41 (2H, c.), 4.69 (1H, c.), 4.87 (1H, c.), 5.03 (1H, s), 5.11 (1H, broad singlet), 6.42 (2H, d, J=7.4 Hz), 6.68 (1H, T. J=7.4 Hz), 7.13 (2H, so J=7.4 Hz).

Experiment 1. The influence of drugs on behavior change caused by the introduction into the sheath of the spinal cord FeCl2in mice.

Used male mice S1c:ICR (age 5 weeks) (10 mice per group). Saline (5 μl/mouse) containing 50 mmol FeCl2, was injected into the subarachnoid space between the 6th lumbar vertebra and the 1st sacral vertebra, and the results were determined in the form of a ball estimates as follows.

The scoring of Behavioral reaction

0 normal

1 strong biting hind legs and lower abdomen, and intense biting the lower body rotation, (b) increased activity and aggressiveness to external stimuli, (C) jitter

Was observed, at least one of AI or both limbs

5 death

Based on the above estimates was calculated the percentage of inhibition. Compound is administered orally 30 minutes before the injection of chloride of iron.

The table shows the average scores and percentages of inhibition obtained by oral administration of 100 mg/kg of compound (I).

The results clearly show that the compounds according to the invention have a high suppressive activity against disorders of the Central nervous system, caused by the formation of lipoperoxide under the action of chloride of iron.

As described above, compound (I) according to the invention possess inhibitory (anti-oxidation) action in respect of education lipoperoxide, inhibitory or suppressive activity against the formation of lipoxygenase and NNT and are useful as drugs for the prevention and treatment of diseases of the cardiovascular system, as well as inflammatory and allergic diseases.

Example 107. 2,2,4,6,7-Pentamethyl-5-phenylamino-2,3-dihydrobenzofuran.

To a solution of 3,5,6-trimethyl-2-(2-methyl-2-propenyl)-4-phenylalaninol (1.40 g, to 4.98 mmol) in methanol (30 ml) was added concentrationcamp in an argon atmosphere for 30 minutes The reaction mixture was cooled, neutralized with an aqueous solution of sodium bicarbonate and was extracted with ethyl acetate. The extract was washed with saturated saline solution and dried with anhydrous sodium sulfate. The solvent was evaporated in vacuo, the residue was recrystallized from isopropyl ether with the formation of the target compound (0.97 g, yield of 69.3%), so pl. 148-151oC.

An NMR spectrum (CDCl3) d 1.49 (6H, c), 2.04 (3H, c), 2.10 (3H, c), 2.12 (3H, c), 2.95 (2H, c), 5.03 (1H, ush. c), 6.42 - 6.48 (2H, m), 6.64-6.72 (1H, m), 7.08-7.17 (2H, m).

Example 108. 2,2,4,6,7-Pentamethyl-5-phenylamino-2,3-dihydrobenzofuran.

Illogical to that described in example 107, obtained a named connection (output 55,8%), so pl. 145-146oC (isopropyl ether - pentane).

An NMR spectrum (CDCl3) d 1.50 (6H, c), 2.01 (3H, c), 2.07 (3H, c), 2.13 (3H, c), 2.31 (3H, c), 2.95 (2H, c), 4.84 (1H, ush. c), 6.09 (1H, DD, J=1.2 and 8.0 Hz), 6.63 (1H, dt, J=1.2 and 8.0 Hz), 6.90-7.00 (1H, m), 7.10 (1H, d, J=7.2 Hz).

Example 109. 2,2,4,6,7-Pentamethyl-5-(2,6-dimethylphenylimino)-2,3 - dihydrobenzofuran.

In the same way as described in example 107, the received titled compound (yield of 58.9%), so pl. 112-113oC (hexane).

An NMR spectrum (CDCl3) d 1.47 (6H, c), 1.88 (3H, c), 1.95 (3H, c), 2.03 (3H, c), 2.11 (3H, c), 2.91 (2H, c), 4.71 (1H, ush. c), 6.67 (1H, t, J=7.6 Hz), 6.92 (1H, d, J=7.6 Hz).

Example 110. 07, received titled compound (yield 60%), so pl. 106-107oC (isopropyl ether pentane).

An NMR spectrum (CDCl3) d 1.49 (6H, c), 2.02 (3H, c), 2.07 (3H, c), 2.12 (3H, c), 2.95 (2H, c), 5.04 (1H, ush. c), 6.36 (2H, d, J=8.8 Hz), 7.06 (2H, d, J= 8.8 Hz).

Example 111. 5-(4-Methoxybenzylamine)-2,2,4,6,7-pentamethyl-2,3 - dihydrobenzofuran.

In the same way as described in example 107, obtained a named connection (output 61,2%), so pl. 117-119oC (isopropyl ether pentane).

An NMR spectrum (CDCl3) d 1.49 (6H, c), 2.04 (3H, c), 2.09 (3H, c), 2.12 (3H, c), 2.95 (2H, c), 3.73 (3H, c), 4.86 (1H, ush. c), 6.41 (2H, d, J=9.0 Hz), 6.73 (2H, d, J=9.0 Hz).

Example 112. 5-Amino-7-methoxy-2,2,4,6-tetramethyl-2,3-dihydrobenzofuran.

To a solution of 7-methoxy-2,2,4,6-tetramethyl-5-nitro-2,3 - dihydrobenzofuran (8,20, a 32.6 mmol) in ethanol (150 ml) was added 10% palladium on coal (8,2 g, purity 50%) and the mixture was stirred for 3 hours in hydrogen atmosphere. The reaction mixture was filtered, and the filtrate was concentrated in vacuum. To the residue was added an excess of aqueous sodium bicarbonate and was extracted with chloroform. The extract was washed with saturated salt solution and dried with anhydrous magnesium sulfate. The solvent was evaporated in vacuum. The residue was led from hexane, had been named connection (6,48 g, o>/P>Example 113. 5-Amino-2-(4-(3,4-acid)piperidino)methyl-2,4,6,7 - tetramethyl-2,3-dihydrobenzofuran.

A mixture of 5-amino-2-methyl bromide-2,4,6,7-tetramethyl-2,3 - dihydrobenzofuran (1.5 g, at 5.27 mmol), 4-(3,4 - acid)piperidine (1.40 g, 6,32 mmol) and triethylamine (2.20 ml, 15.8 mmol) was stirred at 180oC in a sealed vial in an argon atmosphere for 3 hours. The reaction mixture was cooled, neutralized with an aqueous solution of sodium bicarbonate and was extracted with chloroform. The extract was washed with saturated salt solution and dried with anhydrous magnesium sulfate. The solvent was evaporated in vacuum. The residue was purified quick column chromatography (eluent chloroform-methanol, 98: 2), recrystallize from a mixture of ethyl acetate-hexane and received the named compound (1.75 g, yield of 78.2% ). so pl. 129-131oC.

An NMR spectrum (CDCl3) d 1.46 (3H, c), 1.65-1.82 (4H, m), 2.08 (6H, c), 2.11 (3H, c), 2.14-2.43 (3H, m), 2.52 (1H, d, J=15.0 Hz), 2.60 (1H, d, J=15.0 Hz), 2.83 (1H, d, J=15.6 Hz), 2.96 - 3.25 (5H, m), 3.85 (3H, c), 6.73-6.82 (3H, m).

Example 114. 5-Amino-2-/4-(2,4-acid)piperidino/methyl-2,4,6,7 - tetramethyl-2,3-dihydrobenzofuran.

In the same way as described in example 113, obtained a named connection (output 68,4%), so pl. 163-165oC (isopropyl ether ethyl acetate).

Spec is, ), 6.40-6.48 (2H, m), 7.09 (1H, d, J=9.2 Hz).

Example 115. 5-Amino-2-/4-(4-methoxyphenyl)piperidino/methyl-2,4,6,7 - tetramethyl-2,3-dihydrobenzofuran.

In the same way as described in example 113, the received titled compound (yield of 76.8%), so pl. 108-109oC (hexane).

An NMR spectrum (CDCl3) d 1.47 (3H, c), 1.67-1.83 (4H, m), 2.09 (6H, c), 2.11 (3H, c), 2.20-2.48 (3H, m), 2.51-2.68 (2H, m), 2.84 (1H, d, J=15.6 Hz), 2.96-3.08 (1H, m), 3.15 (1H, d, J=15.6 Hz), 3.16 (2H, ush. c), 3.28 (2H, ush. c), 3.79 (d, c), 6.85 (2H, d, J=8.8 Hz), 7.15 (2H, d, J=8.8 Hz).

Example 116. 5-Amino-2-/4-(3-methoxyphenyl)piperidino/methyl-2,4,6,7 - tetramethyl-2,3-dihydrobenzofuran.

In the same way as described in example 113, obtained a named connection (output 75,7%), so pl. 94-95oC (hexane).

An NMR spectrum (CDCl3) d 1.47 (3H, c), 1.76 (4H, ush. c), 2.08 (6H, c), 2.11 (3H, c), 2.18-2.68 (5H, m), 2.84 (1H, d, J=15.4 Hz), 2.95-3.30 (5H, m), 3.80 (3H, c), 6.71-6.85 (3H, m), 7.22 (1H, t, J=8.2 Hz).

Reference example 79. 4-(4-Chlorpheniramine)-3,5,6-trimethyl-2-(2-methyl-2-propenyl)-2,5 - cyclohexadiene-1-it.

To a solution of pyridine (7,13 ml, 88,2 mmol) in 1,2-dichloroethane (40 ml) was added dropwise a titanium tetrachloride (2,42 ml, 22,1 mmol), and after completion of addition the reaction mixture was heated under reflux for 20 minutes in an argon atmosphere. After cooling, to the reaction mixture DOB,2-dichloroethane (20 ml), then this mixture was stirred in argon atmosphere at a temperature of 90oC for 45 minutes. The reaction mixture was cooled and filtered through celite. The filtrate was washed with saturated saline solution, dried and concentrated. The residue was purified by chromatographytandem on silica gel (eluent hexane-ethyl acetate 93:7) with the formation of the target compound (4,43 g, yield 96,0%) as oil.

An NMR spectrum(CDCl3), d: 1.53-2.20 (12H, m), 3.21 (2H, c), 4.51 (1H, c.), 4.74 (1H, c), 6.68 (2H, d, J=8.8 Hz), 7.30 (2H, d, J=8.8 Hz).

Reference example 80. 4-(4-Methoxybenzylidene)-3,5,6-trimethyl-2-(2-methyl-2-propenyl)-2,5-cyclohexadiene-1-it.

In the same way as described in reference example 79, received the named compound as oil (yield of 19.1%).

An NMR spectrum(CDCl3), d: 1.50-1.60 (3H, m), 1.77 (3H, ush. c), 1.95-2.03 (3H, m), 2.25 (3H, ush. c), 3.16-3.25 (2H, m), 3.82 (3, c), 4.46-4.58 (1H, m), 4.74 (1H, ush. c), 6.72 (2H, d J=9.0 Hz), 6.88 (2H, d, J=9.0 Hz).

Reference example 81. 3,5,6-Trimethyl-4-(2-methylphenylimino)-2-(2-methyl-2-propenyl)-2,5-cyclohexadiene-1-it.

In the same way as described in reference example 79, received the named compound as oil (yield 88.1 per cent).

An NMR spectrum(CDCl3) d 1.77 (3H, ush. c), 2.03 (9H, m), 2.18 (3H, c), 3.21 (2H, c), 4.53 (1H, c), 4.74 (1H, c), 6.39 (1H, d, J=7.8 Hz), 7.01 (1H, t, J= 7.8 Hz), 7.10 (1 the enol.

To a solution of 4-(4-chlorpheniramine)-3,5,6-trimethyl-2-(2-methyl-2 - propenyl)-2,5-cyclohexadiene-1-she (and 4.40 g, 14.0 mmol) in tetrahydrofuran (20 ml) was added Hydrosulphite solution of sodium (24.4 g, 0.14 mol) in water (50 ml) and the resulting mixture was stirred at room temperature for 30 minutes. After separation of the organic phase the aqueous phase was extracted with ethyl acetate and the extract was combined with the organic phase. This mixture was washed with water, dried and the solvent was removed in vacuum. The residue was purified by chromatography on columns of silica gel (a mixture of hexane and ethyl acetate, 95:5) with the formation of the target compound (yield 97.2%) in the form of butter.

An NMR spectrum (CDCl3) d 1.80 (3H, c), 2.11 (3H, c), 2.12 (3H, c), 2.19 (3H, c), 3.40 (2H, c), 4.68 (1H, c), 4.87 (1H, c), 5.04 (1H, c), 5.14 (1H, broad singlet), 6.34 (2H, d, J=8.8 Hz), 7.06 (2H, d, J=8.8 Hz).

Reference example 83. 4-(4-Methoxybenzylamine-3,5,6-trimethyl-2-(2-methyl-2-propenyl)phenol.

In the same way as described in reference example 82, received the named compound as oil (yield of 98.2%).

An NMR spectrum (CDCl3) d 1.00 (3H, c), 2.14 (6H, c), 2.19 (3H, c), 3.40 (2H, c), 3.73 (3H, c), 4.69 (1H, c), 4.85-5.05 (3H, m), 6.38 (2H, d, J=8.8 Hz), 6.73 (2H, d, J=8.8 Hz).

Reference example 84. 3,5,6-Trimethyl-4-(2-methylphenylimino-2-(2-methyl-2-propenyl)phenol.

An NMR spectrum (CDCl3) d 1.81 (3H, c), 2.11 (6H, c), 2.20 (3H, c), 3.32 (3H, c), 4.70 (1H, c), 4.85-5.05 (3H, c), 6.03 (1H, d, J=8.0 Hz), 6.65 (1H, t, J= 7.0 Hz), 9.65 (1H, t, J=8.0 Hz), 7.11 (1H, d, J=7.0 Hz).

Reference example 85. 3,5,6-Trimethyl-4-(2,6 - dimethylphenylimino-2-(2-methyl-2 - propenyl)phenol.

To a solution of pyridine (2.38 ml, 29.4 mmol) in 1,2-dichloroethane (20 ml) was added dropwise a titanium tetrachloride (0,81 ml of 7.35 mmol) and the reaction mixture was stirred at 90oC for 20 minutes in an argon atmosphere. After cooling the reaction mixture to it was added a solution of 3,5,6-trimethyl-2-(2-methyl-2-propenyl)-1,4-benzoquinone (1,00 g of 4.90 mmol) in 1,2-dichloroethane (5 ml) and a solution of 2,6-xylidine (1,81 ml, 14.7 mmol) in 1,2-dichloroethane (5 ml), and the mixture was stirred in argon atmosphere at a temperature of 90oC for 30 minutes. The reaction mixture was cooled, was added chloroform and filtered through celite. To the filtrate was added a saturated solution of salt, shook and again filtered through celite. The filtrate was washed with saturated salt solution, dried with anhydrous magnesium sulfate and concentrated in vacuum. The residue was purified by chromatography on columns of silica gel (a mixture of hexane and ethyl acetate, 98:2) and obtained crude product (1,15 g). The compound obtained was dissolved in tetrahydrofuran is stirred at room temperature for 30 minutes. After separation of the organic phase the aqueous phase was extracted with ethyl acetate and the extract was combined with the organic phase. This mixture was washed with saturated salt solution, dried with anhydrous magnesium sulfate, and the solvent is kept at reduced pressure. The residue was purified by chromatographytandem on a column of silica gel (a mixture of hexane and ethyl acetate, 9:1) and received the above compound (0.87 g, yield 57,4%) as oil.

An NMR spectrum (CDCl3) d 1.79 (3H, c), 1.93 (6H, c), 2.05 (6H, c), 2.17 (3H, c), 3.38 (2H, c), 4.67 (1H, c), 4.78 (1H, ush.c), 4.86 (1H, s), 4.90 (1H, s), 6.67 (1H, t, J=7.4 Hz), 6.92 (1H, d, J=7.4 Hz).

Reference example 86. 3,5,6-Trimethyl-2-(2-methyl-2-propenyl)-4-phenylalaninol.

In the same way as described in reference example 85, received the named compound as oil (yield 42.8 per cent).

An NMR spectrum (CDCl3) d 1.79 (3H, c), 2.14 (6H, c), 2.19 (3H, c), 3.41 (2H, c), 4.69 (1H, c), 4.87 (1H, c), 5.03 (1H, s), 5.11 (1H, ush.c), 6.42 (1H, d, J=7.4 Hz), 6.92 (1H, t, J=7.4 Hz).

Preparation 1.

(1) 5-Amino-2,4,6,7-tetramethyl-2-(4-phenylpiperidine)-2,3 - dihydrobenzofuran (example 67) 50 g

(2) Lactose 100 g

(3) Corn starch 15 g

(4) Calcium carboxymethylcellulose 44 g

(5) magnesium Stearate 1 g

1000 tablets 210 g

Components(1), (2), (3) and 30 g of the component (4) was mixed with omponent (5) and the mixture was loaded into tabletiruemuju machine. Received 1000 tablets containing 50 mg of the component (1) each tablet.

The drug 2.

(1) 5-Amino-2,4,6,7-tetramethyl-2-(4-phenylpiperidine)-2,3 - dihydrobenzofuran (example 67) 10 g

(2) Lactose 4.5 g

(3) Corn starch 4.5 g

(4) magnesium Stearate 1 g

100 capsules (20 g

All components are thoroughly mixed, and the mixture was filled gelatin capsules. Received 100 capsules containing 100 mg of the component (1) in each capsule.

The drug 3.

The preparation for injection vials were prepared by mixing and dissolving the following components per ampoule:

5-Amino-2,4,6,7-tetramethyl-2-(4-phenylpiperidine)-2,3 - dihydrobenzofuran (example 67) 50 mg

Sodium chloride 18 mg

Distilled water for injection in the required amount

The total number of 2 million

1. Derivatives aminocoumarin General formula I

< / BR>
where R1and R2may be the same or different and represent a hydrogen atom, benzoyl,1-C6- acyl residue of carboxylic acid; C1-C3- alkylsulfonyl; toluensulfonyl; C1-C5- alkoxycarbonyl; C1-C6-alkyl, possibly substituted by phenyl; phenyl, possibly substituted by a halo atom and or different and are selected from among nitro; amino group, possibly substituted lower alkyl; WITH1-C6-alkoxygroup; C2-C6- alkenyl or1-C6-alkyl, possibly substituted piperidine, morpholine or di(lower)alkyl amino(lower)alkyl; the substituents R6and R7may be the same or different and represents formyl; or (C2-C6alkenyl or1-C6-alkyl, possibly substituted by a hydroxy-group; a halogen atom; C2-C3-acyl group; amino group, possibly mono - or disubstituted by lower alkyl, phenyl, phenyl(lower)alkyl, piperidino(lower)alkyl, pyridine or imidazole; lower alkoxycarbonyl group; phenylthiourea, possibly substituted by a halogen atom or hydroxy-group; phenyl(lower alkyl)diography; C1-C3-alkylthiophene; C1-C3- alkylsulfanyl group; C1-C3-alkylsulfonyl; phenylsulfonyl group; phenylsulfonyl; C1-C3-alkoxygroup, possibly substituted by phenyl or C1-C3-dialkylamino; C5-C6cyclic amino group may optionally having a ring oxygen atom or nitrogen and substituted lower alkyl, phenyl, diphenyl is iridine, the benzothiazole, hydroxy-C1-C6- alkyl or carboxy-C1-C6- alkyl; or imidazolium, provided that at least one of the substituents R6and R7has a methylene fragment in position, and the substituents R8and R9are the same or different and are selected from among a hydrogen atom; C1-C6-alkyl; phenyl, possibly substituted by a halogen atom, a C1-C5- alkylaminocarbonyl or1-C3-dialkylamino; or pyridyl, or their salts.

2. Connection on p. 1, where the group NR1R2are in the position of the 5-th atom kumaranatunga rings.

3. Connection on p. 1, where R1and R2represent hydrogen.

4. Connection on p. 1, where R1represents hydrogen, and R2hydrogen, C1-C6-alkyl or phenyl.

5. Connection on p. 1, where R3, R4and R5are1-C6-alkyl.

6. Connection on p. 1, where R6and R7are1-C6- alkyl.

7. Connection on p. 1, where R6is1-C6-alkyl, and R7WITH1-C6-alkyl, substituted C5-C6- cyclic amino the unity in p. 1, where R6is1-C6-alkyl, and R7phenyl-C1-C6-alkyl.

9. Connection on p. 1, where R8is1-C6-alkyl, and R9the hydrogen.

10. Connection on p. 1, where R8represents hydrogen, and R9- phenyl, optional zameshannyj halogen or1-C6-alkyl.

11. Connection on p. 1 is a hydrochloride 5-amino-2,2,4,6,7-pentamethyl 2, 3-dihydrobenzofuran, 5-amino-2,2,4,6,7-pentamethyl-3-phenyl-2, 3-dihydrobenzofuran, 5-amino - 3-(4-forfinal)-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran, 5-amino-2,2,4,6,7-pentamethyl 3-(3-pyridyl)- 2,3-dihydrobenzofuran, 5-amino-2,2,6,7-tetramethyl-2 - piperidinomethyl-2,3-dihydrobenzofuran, 5-amino-2,4,6,7-tetramethyl-2-morpholinomethyl-2, 3-dihydrobenzofuran, the dihydrochloride of 5-amino-2,4,6,7-tetramethyl-2-[2-(dimethylamino)ethyl] - 2,3-dihydrobenzofuran, the dihydrochloride of 5-amino-2,4,6,7-tetramethyl-2-(2 - piperidinoethyl)-2, 3-dihydrobenzofuran, hydrochloride 5-methylamino-2,2,4,6,7 - pentamethyl-2,3-dihydrobenzofuran,

5-amino-2,4,6,7 - tetramethyl-2-dimethylaminomethyl-2,3-dihydrobenzofuran,

5-amino-2,4,6,7-tetramethyl-2-pyrrolidinone-2,3-dihydrobenzofuran;

5-amino-2,4,6,7-tetramethyl-2-[4-methylpiperazine] methyl-2,3 - dihydrobenzo the reed 5-amino-2-(N-benzylamino)- 2,4,6,7-tetramethyl-2,3-dihydrobenzofuran,

the dihydrochloride of 5-amino-2,4,6,7-tetramethyl-2-(N-phenethylamine)- 2,3-dihydrobenzofuran,

the dihydrochloride of 5-amino-2- (1-imidazolyl)methyl-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran,

5-amino-2,4,6,7-tetramethyl-2-(4-phenylpiperazine)methyl-2,3-dihydrobenzofuran,

5-amino-2,4,6,7-tetramethyl-2- (4-phenylpiperidine)methyl-2,3-dihydrobenzofuran,

the dihydrochloride of 5-Mino-2,4,6,7-tetramethyl-2-/4-/diphenylmethyl/piperidinomethyl/2/- 3-dihydrobenzofuran,

5-amino-2-benzoyloxymethyl-2,4,6,7-tetramethyl-2,3 - dihydrobenzofuran,

5-amino-2-methoxymethyl-2,4,6,7-tetramethyl-2,3 - dihydrobenzofuran,

5-amino-2,4,6,7-tetramethyl-2-/2-/4 forfinal/ethyl/ 2,3-dihydrobenzofuran,

5-amino-2-methyl bromide-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran, hydrochloride 5-amino-2-phenylthiomethyl-2,4,6,7-tetramethyl-2, 3-dihydrobenzofuran,

hydrochloride 5-amino-2-/4-forfinal/thiomethyl-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran,

hydrochloride 5-amino-2/1-Mei-2-yl/thiomethyl-2,4,6,7 - tetramethyl-2,3-dihydrobenzofuran,

hydrochloride 5-amino-2-/2-benzothiazolyl/thiomethyl-2,4,6,7-tetramethyl-2, 3-dihydrobenzofuran,

hydrochloride 5-amino-2-benzyldimethyl-2,4,6,7 - tetramethyl-2,3-dihydrobenzofuran,

5-amino-2,4,6,7 - tetramethyl-2-/4-pyridyl/thiomethyl-2,3-dihydrobenzofuran and is in p. 11, representing hydrochloride 5-amino-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran.

13. Composition for inhibiting the formation of lipoperoxide, characterized in that it comprises an effective amount of the compounds of formula I on p. 1 or its salt, and a carrier, diluent or excipient.

14. The method of obtaining derivatives aminocoumarin General formula I on p. 1, characterized in that the compound of General formula

< / BR>
where R1, R2, R3, R4, R5and R6have the values listed in paragraph 1,

or its salt is subjected to reaction ring closure, and the product resulting from the reaction, ring closure, optional subjected to reaction unprotect, acylation reaction, hydrogenation reaction, oxidation reaction, the reaction lengthening the carbon chain or exchange reactions of substituents, and these reactions may be carried out individually or in combination of two or more reactions.

15. The method of obtaining derivatives aminocoumarin General formula I on p. 1, characterized in that the compound of General formula

< / BR>
where R1, R2, R3, R4and R5have the values listed in paragraph 1,

or its salt is subjected to reaction; the figures for R6in p. 1;

R7matter specified in paragraph 1,

and the reaction product of the condensation is not necessarily subjected to reaction unprotect, reactions, acylation or alkylation reaction, and these reactions may be carried out individually or in combination of two or more of these reactions.

16. The method of obtaining derivatives aminocoumarin General formula I on p. 1, characterized in that the compound of General formula

< / BR>
where R3, R4, R5, R6, R7, R8and R9have the values listed in paragraph 1,

or its salt is subjected to reaction recovery, and the reaction product recovery does not necessarily subjected to reaction unprotect, reactions, acylation or alkylation reaction, and these reactions may be carried out individually or in combination of two or more of these reactions.

 

Same patents:

The invention relates to new chemical substances, which have valuable pharmacological properties, more particularly to a nitrogen-containing heterocyclic compounds of General formula I

< / BR>
where X is oxygen or sulfur;

Y is carbon or nitrogen;

Z is carbon or nitrogen, and Y and Z are not simultaneously mean nitrogen;

R1and R2independent from each other and denote hydrogen, alkyl with 1 to 6 carbon atoms, halogen, trifluoromethyl, nitrile, alkoxy with 1 to 6 carbon atoms, a group of CO2R7where R7means hydrogen or alkyl with 1 to 6 carbon atoms, group-C(O)NR8R9where R8and R9not dependent from each other and denote hydrogen, alkyl with 1 to 3 carbon atoms, methoxy or together with the nitrogen form a morpholine, pyrrolidine or piperidine-NR10R11where R10and R11denote hydrogen or alkyl with 1 to 6 carbon atoms, group-C(O)R12where R12means alkyl with 1 to 6 carbon atoms, group-SO2R12where R12has the specified value, -NHC(O)R12where R12has the specified value, -NHSO2R12where R12has a specified value, and-SO2NR13R14where R13and R142R12where R12has the specified value, -NHC(O)R12where R12has the specified value, -NHSO2R12where R12has the specified value, -SO2NR13R14where R13and R14have a specified value, a nitrogroup, 1-piperidinyl, 2-, 3 - or 4-pyridine, morpholine, thiomorpholine, pyrrolidine, imidazole, unsubstituted or substituted at the nitrogen by alkyl with 1 to 4 carbon atoms, 2-thiazole, 2-methyl-4-thiazole, dialkylamino with 1 to 4 carbon atoms in each alkyl group, or alkilany ether with 1 to 4 carbon atoms;

R4an ester of formula-CO2R16where R16means alkyl with 1 to 4 carbon atoms, the amide of formula C(O)NR17R18where R17and R18independent from each other and denote hydrogen, alkyl with 1 to 2 carbon atoms, methoxy or together with the nitrogen form a morpholine, piperidine or pyrrolidine, phenyl, unsubstituted or substituted by residues from the group comprising halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 to 4 carbon atoms, 3-methyl-1,2,4-oxadiazol-5-yl, 2 - or 3-thienyl, 2-, 3 - or 4-pyridyl, 4-pyrazolylborate 4 stands, the ketone of the formula C(O)R19'where R19means alkyl with 1 to 3 carbon atoms, phenyl or 1-Mei-2-yl, a simple ester of the formula-CH2OR20where R20means alkyl with 1 to 3 carbon atoms, thioether formula-CH2SR20where R20has the specified value, the group CH2SO2CH3amines of the formula-CH2N(R20)2where R20has the specified value, the remainder of the formula-CH2NHC(O)R21where R21means methyl, amino or methylamino - group-CH2NHSO2Me2where Me denotes methyl carbamate of the formula CH2OC(O)NHCH3;

R5and R6independent from each other and denote hydrogen or methyl;

n is 0,1 or 2,

Provided that the substituents are not simultaneously have the following meanings: Y and Z is carbon, R1or R2hydrogen, halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 to 4 carbon atoms, cyano, nitro, trifluoromethyl, R3unsubstituted phenyl and R4group-C(O)OR16'where R16'means hydrogen, alkyl, alkenyl or quinil, group-C(O)N(R18')(R19'), where R18'and R19'denote hydrogen, alkyl with 1 to 6 carbon atoms, phenyl, alkoxy or together with the nitrogen form pyrrolidine, piperidine or morpholine, cyanotic, unsubstituted phenyl and 4-imidazole,

in the form of a racemate or an individual enantiomers and their salts, are inhibitors of leukotriene biosynthesis

The invention relates to new 2-sharonlee heterocyclic carboxylates, inhibiting the enzymatic activity of proteolytic enzymes, containing compositions, to a method of their use for the treatment of diseases associated with degeneration of the tissues, and to a method of production thereof

The invention relates to new benzanilide derivatives, processes for their preparation and the pharmaceutical compositions

The invention relates to organic chemistry, and more specifically to new connections - hydrochloridum 2-aminoimidazole and 2-aminothiazole General formula (1),

< / BR>
aryl, the substituent in position 4 and a disulfide bridge in the position 5, where X is alkylamino, for example, methylamino, and R1-R2is hydrogen; X-methylaminopropyl, and R1-alkyl, for example methyl and R2is hydrogen; X-methylaminopropyl, and R1-alkoxygroup, for example, methoxy and R2is hydrogen; X-methylaminopropyl, and R1-ethoxypropan and R2is hydrogen; X-methylaminopropyl, and R1halogen, for example chlorine and RF2is hydrogen; X-methylaminopropyl, and R1-R2-alkoxygroup, for example, methoxy; X-atramentaria, and R1-alkoxygroup, for example, methoxy and R2is hydrogen; X is sulfur, and R1-alkoxygroup, for example, methoxy and R2is hydrogen; X is sulfur, and R1-R2-alkoxygroup, for example, methoxy; X is sulfur, and R1halogen, for example fluorine and R2-hydrogen

The invention relates to new heterocyclic derivatives of substituted 2-acylamino-5-thiazolo exhibiting affinity to the receptor cholecystokinin and gastrin to a method for producing such compounds and to pharmaceutical compositions based on

The invention relates to new derivatives of 3(2H)-pyridazinone and to their pharmaceutically acceptable salts, possessing inhibitory activity against the aggregation of platelets, cardiotonic activity, vasodilating activity, anti-SRS-A activity, to processes for their preparation and to pharmaceutical compositions containing them as active ingredient

The invention relates to new derivatives of 3(2H)-pyridazinone and to their pharmaceutically acceptable salts, possessing inhibitory activity against the aggregation of platelets, cardiotonic activity, vasodilating activity, anti-SRS-A activity, to processes for their preparation and to pharmaceutical compositions containing them as active ingredient
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