Novel coumarin derivatives with anti-tumour activity

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (11) given below and pharmaceutically acceptable salts thereof: chemical formula 1

in which: each of G1, G2, G3 and G8 independently denotes -N=, -CR1= or -C(-G9-X)=; one of G1, G2, G3 and G8 is-C(-G9-X)=; X is C1-6 alkyl (where C1-6 can be optionally substituted with a group selected from a halogen atom, hydroxy, cyano and -NR56R57), aryl, heterocycle (where the heterocycle denotes a 5-9-member saturated or unsaturated cyclic group containing one or more heteroatoms selected from nitrogen, oxygen and sulphur atoms, and can be a monocycle or condensed ring, and can be optionally substituted with a halogen atom, C1-6 alkyl; C1-6 alkoxy, R33R34NCS-, R3R4NCO-); G9 denotes a single bond, an oxygen atom, a sulphur atom, ring G6 denotes a divalent aryl group or divalent pyridyl group (where the divalent pyridyl group can be optionally substituted with a halogen atom); A is a group of formula (2) given below, or a group of formula (3) given below. Chemical formula 2

, chemical formula 3 , G4 is an oxygen atom or sulphur atom; G5 is an oxygen atom or sulphur atom; G7 is an oxygen atom, -CR42R43-, -CONR44-, -NR44CO, -NR45-, CR42R43NR45-, -S-, -NR44S(=O)2-; R1 is a hydrogen atom, a halogen atom, cyano, C1-6 alkyl (where C1-6 alkyl can be optionally substituted with a halogen atom), carbamoyl or C2-7 alkynyl (where C2-7 alkynyl can be optionally substituted with C1-4 acyl); when G2 or G3 denotes -CR1=, then G8 is -C(-G9-X)=, and X is R3R4NCO-, R33R34NCS-; when G8 is -CR1=, then G3 denotes -C(-G9-X)=, and X is R3R4NCO, or R33R34NCS-; when G1 or G8 denotes -CR4 then G2 is -C(-G9-X)=, and X denotes R3R4NCO-, or R33R34NCS-; or when G2 is -CR1=, then G1 denotes -C(-G9-X)=, and X denotes R3R4NCO-, or R33R34NCS-; R1 can form a single bond or -CH2- with R4 or R34; R2 denotes hydroxy or C1-6 alkyl (where C1-6 alkyl can be optionally substituted with a group selected from a halogen atom, hydroxy, C1-6 alkoxy, formyl and -CO2R50); R3, R4, R9 and R10 each independently denotes a hydrogen atom, C3-8 cycloalkyl or C1-6 alkyl (where C1-6 alkyl can be optionally substituted with a group selected from cyano, a halogen atom, hydroxy, C1-6 alkoxy, -NR13R14, and CONR28R29); R6 and R7 each independently denotes a hydrogen atom, C1-6 alkoxy, C3-8 cycloalkyl or C1-6 alkyl (where C1-6 alkyl can be optionally substituted with a group selected from cyano, halogen atom, hydroxy, C1-6 alkoxy, -NR13R14, and CONR28R29); R33 and R34 each independently denotes a hydrogen atom, C1-6 alkyl, the combination of R3 and R4 together with a nitrogen atom to which they are bonded can form a 5-6-member heterocyclic group containing at least one nitrogen atom (where the 5-6-member heterocyclic group which contains at least one nitrogen atom is a saturated or unsaturated heterocyclic group containing 5-6 atoms in the ring and which, in addition to one or more nitrogen atoms, can contain one or more heteroatoms selected from oxygen and sulphur atoms (where the 5-6-member heterocyclic group can be optionally condensed with a benzene ring); and which can be optionally substituted with a halogen atom or C1-6 alkyl; the combination of R6 and R7 together with the nitrogen atom to which they are bonded can form a 5-6-member heterocyclic group containing at least one nitrogen atom (where the 5-6-member heterocyclic group which contains at least one nitrogen atom is a saturated or unsaturated heterocyclic group containing 5-6 atoms in the ring and which, in addition to one or more nitrogen atoms, can contain one or more heteroatoms selected from oxygen and sulphur atoms (where the 5-6-member heterocyclic group can be optionally condensed with a benzene ring); and which can be optionally substituted with a halogen atom, C1-6 alkyl or an oxo group; R45 is a hydrogen atom, R13 and R14 each independently denotes a hydrogen atom, C1-6 alkyl or COR32; R56 and R57 each independently denotes a hydrogen atom or C1-6 alkyl, and R5, R8, R28, R29, R32, R42, R43, R44, and R50 each independently denotes a hydrogen atom or C1-6 alkyl. The invention also relates to a pharmaceutical composition, as well as to a medicinal agent for treating cell proliferative disorder.

EFFECT: obtaining novel biologically active compounds having inhibitory effect on cell proliferation.

15 cl, 2 tbl

 

The technical field to which the invention relates

The present invention relates to a new coumarin derivative having antitumor activity, and to pharmaceutical compositions containing it as active ingredient, in particular a drug for the treatment of cellular proliferative disorders.

The level of technology

It was found that coumarin derivatives, i.e. compounds which have a skeleton of coumarin as the core and in which the skeleton derivation in different positions, have different pharmacological effects depending on the situation, which is chemical modification (non-patent document 31). For example, warfarin, has anti-platelet activity, is a well-known medicinal product with the coumarin skeleton (non-patent document 1). In addition, as a result of chemical modifications at various positions of the cores obtained coumarin derivatives exhibiting anti-tumor activity mediated effects on different proteins target, or coumarin derivatives inhibiting proteins associated with antitumor activity.

It was reported a derivative of coumarin, which exhibits antitumor activity through inhibition of steroid sulfatase (repatent the e documents 2-6). Currently it is undergoing clinical trials. This compound forms cycloalkyl group in positions 3 and 4 of the coumarin skeleton and has a sulphamate group in position 7. From the point of view of its pharmacological actions envisaged its use for the treatment of breast cancer.

In addition, it was reported about a group of compounds related to the derivatives of coumarin, with a characteristic substituent in position 4, showing antitumor activity by binding with receptor for estrogen. In particular, there are reports of a group of compounds with arylalkyl group in position 4 and substituents in positions 3 and 7 (patent document 1) and a group of compounds in which the phenyl group is directly linked to the skeleton in position 4 and which are fenoxaprop in position 3 (patent document 2).

It was also reported derivative of coumarin with Raf inhibitory activity and antitumor activity in the cells, the compound having a 6-personalantispy in position 7 (patent document 5).

In addition, there are several coumarin derivatives, which remain unknown to the target proteins and reported that they exhibit antitumor activity. They include a group of compounds from natural sources (non-patent documents 7-12) and the new group is connected to the th, obtained by chemical synthesis (non-patent documents 13-23, 32-34). It was reported about the new compounds obtained by chemical synthesis, e.g., about connection alkoxygroup in positions 5, 6 and 7 of the coumarin skeleton (non-patent document 13); connection alkoxygroup only in position 7 of the coumarin skeleton (non-patent document 14); the connection with aronovoy functional group in position 6 or 7 of the coumarin skeleton (non-patent document 15); the connection with the methyl group in position 4 of the coumarin skeleton and substituents in positions 7 and 8 (non-patent document 16); the connection with the substituents in all positions 4, 5, 6, 7 and 8 skeleton coumarin derivatives (non-patent document 17); the connection in which the amide group, ether group or sulfonamidnuyu group directly linked to the coumarin skeleton in position 3 and which has a substituent in position 6 or 8 (non-patent documents 18 and 19); the connection in which the amide group is directly connected with the coumarin skeleton in position 3 and which has a substituent at position 7 (patent document 3 and non-patent document 20); the connection with substituents in positions 6 and 7 of the coumarin skeleton (non-patent document 21); the compound having a hydroxyl group in position 7 the coumarin skeleton and the nitro-group in the relevant provisions of 3, 6 and 8 (non-patent documents 22 and 23); and the connection with metox is - or hydroxy-group in position 7 of the coumarin skeleton, the phenyl group in position 3, and the substituent in position 4.

It was also reported: the connection with the Deputy to the nitrogen atom (diphenylamino etc) in regulation 7, the cyano in position 4 and heteroaryl group in position 3 (without optional substituent in position 4) (non-patent document 32); and the connection of the heteroaryl group in position 3 and a methyl group, a halogen atom, a nitro-group, etc. in position 6, 7 or 8 (non-patent document 33). It was also reported examples of the application of compounds with the structure of coumarin derivatives as a ligand Pd compounds with antitumor activity in cells (non-patent document 34).

There are reports of the compounds exhibiting inhibitory activity against protein targets and probably with antitumor activity despite the lack of evidence of antitumor activity related coumarin derivatives exhibiting inhibitory activity for TNFα (patent document 4 and non-patent document 24-28); inhibitory activity for aromatase (non-patent document 29), inhibitory activity for MEK (non-patent document 30) or the like. In the compounds mentioned in these messages, the substituents are in positions 3, 4, 6, or 7 of the coumarin skeleton.

As mentioned above, despite the fact that we know the number of the coumarin derivatives with antitumor activity, few compounds have a sufficiently high antitumor activity in order that they can be used in practice as an anticancer drug. Therefore, carried out an intensive search of more suitable for the practice of compounds with high anti-tumor activity.

Patent document 1: International Publication WO 2000/039120.

Patent document 2: International Publication WO 2004/069820.

Patent document 3: International Publication WO 2003/024950.

Patent document 4: International Publication WO 2002/008217.

Patent document 5: International Publication WO 2006/067466.

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Non-patent document 3: Lloyd M.D., Pederick R.L., Natesh, R., Woo L.W.L., Purohit, A., Reed M.J., K.R. Acharya, B.V.L. Potter, Biochem. J., 2005, 385, 715-720.

Non-patent document 4: Purohit, A., Woo L.W.L., B.V.L. Potter, M.J. Reed, Cancer Research 2000, 60, 3394-3396.

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Non-patent document 17: Kimura s, Ito C, Jyoko N., Segawa H., Kuroda, J., Okada, M., Adachi, S., Nakahata, T., Yuasa, T., Filho V.C., H. Furukawa, out by Maekawa I., Int. J. Cancer 2005, 113, 158-165 (in Russian).

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The invention

The purpose of this invention is the provision of a compound that has a sufficiently high antitumor activity is updated and which is suitable as pharmaceuticals for the treatment of cell proliferative disorders, in particular cancer, and pharmaceutical compositions containing the compound as an active ingredient.

The applicants of the present invention conducted intensive studies in order to obtain new compounds effective for the treatment of cell proliferative disorders, in particular cancer, and found that coumarin derivative having substituents at the 3, 4 and 7 of the coumarin skeleton, which may have a substituent in the 6 position and which contains sulfa group or α-aminomethanesulfonic group, is a compound which has high antitumor activity or which has a high antitumor activity and has a high system availability. The present invention is carried out on the basis of this established fact.

The present invention relates to a compound of General formula (11)below, or its pharmaceutically acceptable salt:

Chemical formula 1

in which:

G1, G2, G3or G8each independently represents-N=, -CR1= or-C(-G9-X)=;

one of the G1, G2, G3or G8is-C(-G9-X)=;

X represents C1-6alkyl (where C1-6the alkyl may be optionally substituted by a group selected from halogen atom, hydroxy, cyano and NR 56R57), aryl, heterocycle, R31CS-, R31CO-, R33R34NCS-, R33R34NC=NH-, R3R4NCO or R33R34NCO2-;

G9represents a simple bond, oxygen atom, sulfur atom, -(CR35R36)1(where 1 is an integer from 1 to 3) or-NR37-;

cycle G6represents a divalent aryl group or divalent heterocyclic group;

A represents a group of General formula (2)below, or a group of the General formula (3)below:

Chemical formula 2

Chemical formula 3

G4represents an oxygen atom, a sulfur atom, -NR38or CR40R41-;

G5represents two hydrogen atoms or an oxygen atom, a sulfur atom or =CH2;

G7represents an oxygen atom, -CR42R43-, -CR42R43-O-, -O-CR42R43-, -CONR44-, -NR44CO-, -NR45-, -NR45CR42R43-, -CR42R43NR45-, -S(=O)n-, -NR44S(=O)n-, -S(=O)nNR44- (where n is an integer from 0 to 2), -N=CR42-, -CR42=N-, -CR42=CR43-, -C≡C-, -NR44-O-, -O-NR44-, -C(=O)-O - or-O-C(=O)-;

R1represents a hydrogen atom, halogen atom, cyano, C1-6alkyl (where C1-6the alkyl may be optionally is amesen group, selected from halogen atom, hydroxy, and-NR46R47)2-7alkenyl, carbarnoyl or2-7quinil (where C2-7quinil may be optionally substituted C1-4the acyl);

when G2or G3represents-CR1=, G8is-C(-G9X)=, and X represents R3R4NCO-, R33R34NC=NH - or R33R34NCS-; when G8is- (CR1=, G3represents-C(-G9-X)=, and X represents R3R4NCO-, R33R34NC=NH - or R33R34NCS-; when G1or G8is- (CR1=, G2is-C(-G9-X)=, and X represents R3R4NCO-, R33R34NC=NH - or R33R34NCS-; or when G2is-CR1=, G1represents-C(-G9-X)=, and X represents R3R4NCO-, R33R34NC=NH - or R33R34NCS-; R1can form a simple bond or-CH2- R4or R34;

R2represents hydroxy, C1-6alkoxy, -NR48R49or1-6alkyl (where C1-6the alkyl may be optionally substituted by a group selected from halogen atom, hydroxy, C1-6alkoxy, formyl, CO2R50and-CO2NR51R52);

R3, R4, R6, R7, R9, R10, R31, R46and R47each independently depict the place of a hydrogen atom, With1-6alkoxy, C3-8cycloalkyl or1-6alkyl (where C1-6the alkyl may be optionally substituted by a group selected from cyano, halogen atom, hydroxy, C1-6alkoxy, -NR13R14, -CONR28R29and aryl);

R33and R34each independently represents a hydrogen atom, a C1-6alkyl or aryl;

the combination of R3and R4the combination of R6and R7the combination of R9and R10the combination of R33and R34and the combination of R46and R47may form together with the nitrogen atom to which they relate, 4-6-membered heterocyclic group containing at least one nitrogen atom (where the heterocyclic group may be optionally condensed with benzene ring);

one group R35and one group R36each independently represents a hydrogen atom, a halogen atom or With1-6alkyl;

R45represents a hydrogen atom, a C1-6alkyl or-S(=O)mNR54R55(where m is an integer from 0 to 2);

R13, R14, R56and R57each independently represents a hydrogen atom, a C1-6alkyl,

-COR32or-CO2R32; and

R5, R8, R28, R29, R32, R37, R38, R40, R41, R42, R43, R44, R48, R49, R50, R51, R52, R4 and R55each independently represents a hydrogen atom or a C1-6alkyl.

G1, G2and G3each independently preferably represents-CR1=and G1and G3more preferable are-CH=.

G8preferably is-C(-G9-X)=. As examples of-X-G9"I can bring the following groups:

When G2or G3represents-CR1=, G8is-C(G9-X)=, and X represents R3R4NCO-, R33R34NC=NH or R33R34NCS-; when G8represents-CR1=, G3is-C(G9-X)=, and X represents R3R4NCO-, R33R34NC=NH or R33R34NCS-; when G1or G8represents-CR1=, G2is-C(G9-X)=, and X represents R3R4NCO-, R33R34NC=NH or R33R34NCS-; or when G2represents-CR1=, G1is-C(G9-X)=, and X represents R3R4NCO-, R33R34NC=NH - or R33R34NCS-; R1can form a simple bond or-CH2together with R4or R34.

As examples of incomplete structures formed when tie is the so called R 1and R4we can note the following partial structure:

Specifically, you can include the following incomplete patterns:

where combinations of G9, Z4, R3, G1and G3have the meanings given in the table below.

where combinations of G9, Z3, R3, G1and G2have the meanings given in the table below.

When G9is -(CR35R36)1(where 1 is an integer from 1 to 3), X preferably represents R33R34NCO2-.

When X represents C1-6alkyl (where C1-6the alkyl may be optionally substituted by a group selected from halogen atom, hydroxy, cyano, and-NR56R57), and G9is a simple bond, R1preferably represents a hydrogen atom, halogen atom, cyano, C2-7alkenyl, carbarnoyl or2-7quinil (where C2-7quinil may be optionally substituted C1-4the acyl).

The compound of General formula (11) is preferably a compound of General formula (1)below.

Chemical formula 1

in which X represents heteroaryl or R3R4NCO-;

Y1and Y2each independently represents-N= or-CR11=;

Y3and Y4may be the same or different and each represents-CR12=;

And is a group of the General formula (2)below, or a group of the General formula (3)below:

Chemical formula 2

Chemical formula 3

R1represents a hydrogen atom, halogen atom, cyano, C1-6alkyl, C2-7alkenyl, carbarnoyl or2-7quinil (where C2-7quinil may be optionally substituted C1-4the acyl);

R2is1-6alkyl, optionally substituted by a halogen atom;

R3, R4, R6, R7, R9and R10each independently represents a hydrogen atom, a C1-6alkoxy, C3-8cycloalkyl or1-6alkyl (where C1-6the alkyl may be optionally substituted by a group selected from cyano, halogen atom, hydroxy, C1-6alkoxy,

-NR13R14);

the combination of R3and R4the combination of R6and R7and the combination of R9and R10may form together with the nitrogen atom to which they relate, 4-6-membered heterocyclic group containing at least one nitrogen atom;

5, R8, R13and R14each independently represents a hydrogen atom or a C1-6alkyl;

R11represents a hydrogen atom, a halogen atom, a C1-6alkyl, C1-4acyl, C1-4acyloxy or-NR15R16;

R12represents a hydrogen atom, a halogen atom or With1-6alkyl;

R15and R16each independently represents a hydrogen atom or a C1-4acyl.

The above compound or its pharmaceutically acceptable salt has a more improved properties as an anticancer drug in comparison with the normal derivative of coumarin, because it has a significantly higher antitumor activity compared with the usual derivative or because it has a higher antitumor activity, which is similar to that of the normal derivative, and has a higher system availability compared to the normal derivative of coumarin.

The above compound or its pharmaceutically acceptable salt, having such properties can be used as an active ingredient of the pharmaceutical composition. Therefore, the present invention relates to pharmaceutical compositions containing a compound of General formula (11), preferably the General formula (1)or its pharmaceutical the ski acceptable salt as an active ingredient.

In addition, the above compound or its pharmaceutically acceptable salt can be used as an active ingredient of a medicinal product for the treatment of cell proliferative disorders, in particular cancer. Therefore, the present invention also relates to a medicinal product for the treatment of cell proliferative disorders, in particular cancer, containing the compound of General formula (11), preferably the General formula (1), or its pharmaceutically acceptable salt as an active ingredient.

The present invention provides a compound which has a sufficiently high antitumor activity and which is suitable as pharmaceuticals for the treatment of cell proliferative disorders, in particular cancer, and pharmaceutical compositions containing the compound as an active ingredient.

Description of the preferred embodiments of the invention

Below will be described the preferred embodiments of the present invention.

The compound of the present invention represented by the General formula (11)above, preferably the General formula (1)above.

In the General formulas (11) and (1) heteroaryl means 5-10-membered aromatic heterocyclic group containing ar is n or more heteroatoms, selected from atoms of oxygen, nitrogen and sulfur. As specific examples are furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolin, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, benzofuranyl, benzothiazol, benzothiadiazoles, benzothiazolyl, benzoxazolyl, benzoxadiazole, benzimidazolyl, indolyl, isoindolyl, indazoles, hinely, ethanolic, cinnoline, hintline, honokalani, indolizinyl and imidazopyridine, among which thiazolyl, pyrimidinyl, pyridyl and the like are preferred, and thiazol-2-yl, pyrimidine-2-yl, 2-pyridyl and the like are particularly preferred.

Heteroaryl may be optionally substituted by a halogen atom, a C1-6the alkyl, C1-6alkoxy, cyano, amino, carbamoyl, nitro, carboxy, C2-7alkenyl,2-7the quinil or the like on the atom cycle, but preferably it is unsubstituted.

Aryl means an aromatic hydrocarbon group containing 6 to 10 carbon atoms. As specific examples are phenyl, 1-naphthyl and 2-naphthyl. The aryl may be optionally substituted by a halogen atom, a C1-6the alkyl, C1-6alkoxy, cyano, amino, carbamoyl, nitro, carboxy, C2-7alkenyl,2-7alkenylamine the like on the carbon atom.

Divalent aryl group means a group obtained by removing any one of hydrogen atoms in the atoms of the above aryl group. Divalent aryl group can be substituted by G7and As in any manner, and when the divalent aryl group is phenylene, it may be, for example, 1,2-substituted, 1,3-substituted or 1,4-substituted.

The halogen atom means a fluorine atom, chlorine, bromine or iodine.

With1-6alkyl means an alkyl group with straight or branched chain containing 1-6 carbon atoms. As specific examples are methyl, ethyl, n-propyl, isopropyl, n-butyl, secondary butyl, tert-butyl, 1-methylpropyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl, 1,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl and 2-ethylbutyl.

With2-7alkenyl means alkenylphenol group with a straight or branched chain containing 2 to 7 carbon atoms. As specific examples are vinyl, allyl, 1-butenyl, 2-butenyl, 3-butenyl, pentenyl, pentadienyl, hexenyl, hexadienyl, heptenyl, heptadienyl and heptatriene.

With2-7quinil means alkylamino group with the nternet or branched chain, containing 2-7 carbon atoms. As specific examples ethinyl, 1-PROPYNYL, 2-PROPYNYL, 1-butynyl, 2-butynyl, 3-butynyl, pentenyl, pentadienyl, hexenyl, hexadienyl, heptenyl, heptadienyl and heptatriene.

With1-4acyl means an acyl group containing 1-4 carbon atoms. As specific examples are formyl, acetyl, n-propionyl, Isopropenyl, butyryl and secondary butyryl (isobutyryl).

With1-6alkoxy means CNS group containing as alkyl alkyl group with straight or branched chain having 1-6 carbon atoms. As specific examples are methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, pentox, hexose.

With3-8cycloalkyl means 3-8-membered cyclic alkyl group, which in General contains 3-8 carbon atoms (where the cyclic alkyl group may be optionally substituted by alkyl straight or branched group containing 1-3 carbon atoms). As specific examples are: unsubstituted cycloalkyl groups, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl; and substituted cycloalkyl groups, such as methylcyclopropyl, ethylcyclopropane, dimethylcyclopropene, trimethylpropyl, dietetica the filing, atelecyclidae, dimethylaminopropyl, diethylethylenediamine, methylcyclobutane, ethylcinnamate, dimethylcyclobutyl, trimethylcyclohexyl, tetramethylcyclobutane, diethylcarbamoyl, ethylmethylthiambutene, dimethylcyclobutyl, methylcyclopentene, ethylcyclopentane, dimethylcyclobutyl, trimethylcyclohexanol, ethylmethylamine, methylcyclohexyl, ethylcyclohexyl, dimethylcyclohexyl and methylheptan, among which are unsubstituted cycloalkyl group are preferred, and cyclopropyl is especially preferred.

4-6-membered heterocyclic group containing at least one nitrogen atom, means a saturated or unsaturated heterocyclic group containing 4-6 atoms in the ring, and optionally one or more nitrogen atoms may contain one or more heteroatoms selected from oxygen atom and sulfur, where the heterocyclic group may be optionally condensed with a benzene ring). As specific examples azetidinol, pyrrolidinyl, piperidinyl, piperazinil, pyrrolyl, dihydropyrrole, imidazolyl, imidazolyl, imidazolidinyl, pyrazolyl, pyrazolyl, pyridazinyl, oxazolyl, oxalidales, morpholinyl, thiomorpholine, pyridinyl, dihydropyridines, pyrazinyl, pyrimidinyl and pyridazinyl.

4-6-membered heterocycle which economic group, containing at least one nitrogen atom may be optionally substituted by a halogen atom, a C1-6the alkyl, C1-6alkoxy, cyano, amino, carbamoyl, nitro, carboxy, C2-7alkenyl,2-7the quinil or the like on the atom cycle.

Heterocyclic group means 4-12-membered, preferably 5 to 7-membered, saturated or unsaturated cyclic group containing one or more heteroatoms selected from nitrogen atoms, oxygen and sulfur. A heterocycle may be a monocycle or a condensed cycle, and its examples include the above heteroaryl group, and the above 4-6-membered heterocyclic group containing one or more nitrogen atoms.

As specific examples of the heterocyclic groups can be lead: furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolin, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, benzofuranyl, benzothiazol, benzothiadiazoles, benzothiazolyl, benzoxazolyl, benzoxadiazole, benzimidazolyl, indolyl, isoindolyl, indazoles, hinely, ethanolic, cinnoline, hintline, honokalani, indolizinyl, imidazopyridine, azetidine, pyrrolidine, piperidinyl, piperazinil, pyrrolyl, dihydropyrrole, imidazolyl, imide oliner, imidazolidinyl, pyrazolyl, pyrazolyl, pyridazinyl, oxazolyl, oxazolidinyl, morpholinyl, thiomorpholine, pyridinyl, dihydropyridines, pyrimidinyl, pyridazinyl, tetrahydrofuryl, tetrahydrothieno, DIOXOLANYL, oxathiolane, dioxane, isobenzofuranyl, bromanil, indolizinyl, indolyl, isoindolyl, indazoles, peril, hinolinol, ethenolysis, chinoline, phthalazine, naphthylidine, honokalani, hintline, cinnoline, pteridine, isopropanol, bromanil, hinokitiol, oxocyclohexyl, dioxocyclohexa, tallowate and disallowable.

Heterocyclic group may be optionally substituted by a halogen atom, a C1-6the alkyl, C1-6alkoxy, cyano, amino, carbamoyl, nitro, carboxy, C2-7alkenyl,2-7the quinil or the like on the atom cycle.

The divalent heterocyclic group means a group obtained by removing any one of hydrogen atoms in the atoms of the above heterocyclic group. The divalent heterocyclic group may be substituted by G7and As in any manner, and when the divalent heterocyclic group is pyridinyl, it may be, for example, 2,3-substituted, 2,4-substituted, 2,5-substituted, 2,6-substituted, 3,4-substituted, 3,5-substituted, 3,6-substituted, 4,5-substituted, 4,6-substituted or 5,6-substituted.

With1-4acyl is XI means acyloxy, containing as the acyl group, acyl group having 1-4 carbon atoms. As specific examples of formyloxy, atomic charges, n-propionyloxy, isopropionate, butyryloxy and secondary butyryloxy (isobutyryloxy).

As concrete examples of C1-6of alkyl, substituted by a halogen atom, it may be permitil, deformity, trifluoromethyl, foradil, defloratin, triptorelin, pentafluoroethyl, forproper, direcror, cryptochromes, heptafluoropropyl, terbutyl, deformaty, tripcomputer, terpencil, divecenter, triterpenes, tetraterpenes, forgather, deftarget, triptorelin, tetraphthalate, pentaverate, chloromethyl, dichloromethyl, trichloromethyl, chloroethyl, dichloroethyl, trichloroethyl, pentachloride, chloropropyl, dichloropropyl, trichlorpropane, heptafluoropropyl, chlorbutol, dichloroethyl, trichloroethyl, chloropentyl, dichlobenil, trichlorophenyl, tetrachlorophenyl, chlorethyl, dichlorethyl, trichlorethyl, tetrachloroethyl, pentachlorphenol, methyl bromide, dibromomethyl, tribromoethyl, bromacil, dibromoethyl, tripometer, pentabromide, bromopropyl, dibromopropyl, dibromopropyl, heptabromo, bromobutyl, dibromoethyl, tribromoethyl, bromopentyl, dibromophenyl, tribromophenyl, tetrabromphenol, bragatel, dibromoethyl, tripometer, tetrabromphenol, pentabromophenyl, IODM the Tyl, diameter, triacetyl, iodates, diodati, tridecyl, pentadecyl, jumpropes, ditropis, ThreadPool, getidprepod, edbutil, diodati, tributyl, iopentol, deadpencil, treatmentil, tetraiodide, yozgatli, diodati, treadwater, tetrahydrate and pentahydrate.

In relation to R1, a hydrogen atom, halogen atom, cyano, C1-6alkyl, carbarnoyl and C2-7quinil (where C2-7quinil may be optionally substituted C1-4the acyl) are preferable; a hydrogen atom, halogen atom, cyano, methyl, ethynyl and acetylator are especially preferable; a hydrogen atom, a halogen atom and methyl are more preferable; and a hydrogen atom, a fluorine atom, a chlorine atom and methyl are even more preferred.

In relation to R2then With1-6alkyl, optionally substituted by a fluorine atom is preferred; methyl, ethyl, n-propyl, vermeil, 1-foretel, 2-foretel, 2,2-dottorati, 1-fluoro-n-propyl, 2-fluoro-n-propyl and 2,2-debtor-n-propyl are particularly preferred; and CH3, -CH2F or-CH2CH3are even more preferred.

R3, R4, R6, R7, R9and R10each preferably represents a hydrogen atom or a C1-6alkyl. In regard With the1-6of alkyl, methyl, ethyl, n-propyl and the propyl are preferred, and methyl, ethyl and isopropyl are particularly preferred.

R3and R4each preferably represents C1-6alkyl. More preferred is when both R3and R4are the same With1-6alkyl groups, particularly methyl groups.

R6and R7each preferably represents a hydrogen atom, a C1-6alkoxy, C3-8cycloalkyl or1-6alkyl (where C1-6the alkyl may be optionally substituted by a group selected from cyano, halogen atom, hydroxy, C1-6alkoxy, -NR13R14). In regard With the1-6alkoxy, representing R6or R7, methoxy, ethoxy are preferred, and methoxy is particularly preferred. In regard With the3-8cycloalkyl representing R6or R7then the unsubstituted cycloalkyl is preferred, and cyclopropyl is especially preferred. In regard With the1-6of alkyl, representing R6or R7, methyl, ethyl and n-propyl are preferred, while ethyl is particularly preferred when1-6alkyl is substituted, and methyl is particularly preferred when1-6unsubstituted. Halogen atom, selected as Deputy1-6the alkyl preferably represents the volume of fluorine. With1-6alkoxy, selected as Deputy1-6the alkyl, preferably is methoxy.

In relation to R6and R7each more preferably represents a hydrogen atom, an unsubstituted cycloalkyl or unsubstituted With1-6alkyl. Regarding the combination of R6and R7, preferred are combinations of: hydrogen atoms; a hydrogen atom and methyl; hydrogen atom and cyclopropyl; a methyl group; a hydrogen atom and cyanoethyl; the hydrogen atom and methoxyethyl; the hydrogen atom and aminoacyl; the hydrogen atom and triptorelin; a hydrogen atom and methoxy; a hydrogen atom and hydroxyethyl; and a hydrogen atom and methylaminomethyl; and especially preferred are combinations of: hydrogen atoms; the hydrogen atom and cyclopropyl; and a hydrogen atom and methyl.

R9and R10each preferably represents a hydrogen atom, a C1-6alkyl or C1-6alkoxy. In regard With the1-6of alkyl, methyl, ethyl, n-propyl and isopropyl are preferred, and methyl, ethyl and isopropyl are particularly preferred. In regard With the1-6alkoxy, methoxy, ethoxy, n-propoxy, isopropoxy are preferred, and methoxy is particularly preferred.

Regarding the combination of R9and R10, preferred are combinations of: hydrogen atoms; a hydrogen atom and methyl; METI the performance communications group; the atom of hydrogen and ethyl; ethyl group; a hydrogen atom and isopropyl; methyl and isopropyl; ethyl and isopropyl; ISO-propyl group; a hydrogen atom and methoxy; methyl and methoxy; ethyl and methoxy; and isopropyl and methoxy, and especially preferred are combinations of: hydrogen atoms; a hydrogen atom and methyl; methyl group; a hydrogen atom and ethyl; a hydrogen atom and isopropyl; and a hydrogen atom and methoxy.

R5and R8preferably represent a hydrogen atom.

In regard With the1-4acyl, representing R15or R16, formyl, acetyl and propionyl are preferred, and acetyl is particularly preferred. Regarding the combination of R15and R16, preferred are combinations of: hydrogen atoms; and atoms of hydrogen and acetyl; and a combination of hydrogen and acetyl is particularly preferred.

In regard With the1-6of alkyl, representing R11, methyl, ethyl and n-propyl are preferred, and methyl is particularly preferred. In regard With the1-4acyl, representing R11, formyl, acetyl and n-propyl are preferred, and acetyl is particularly preferred. In regard With the1-4acyloxy representing R11then formyloxy, atomic charges and n-propionyloxy are preferred, and the atomic charges is W is preferred. In relation to R11, preferred are a hydrogen atom and halogen atom and a hydrogen atom and a fluorine atom are particularly preferred.

In relation to the Y1then-N=, -CH=, -CF=- CCl= are preferred; -N=, -CH= and-CF= are particularly preferred; and N= and-CH= are even more preferred.

In relation to R11in-CR11representing the Y2then a hydrogen atom, a halogen atom, a C1-4acyl, and-NR15R16are preferred, and hydrogen atom, fluorine atom and chlorine, acetyl and-NH3are particularly preferred. In relation to the Y2then-N=, -CH= and-CF= are preferred, and-CH= and-CF= are particularly preferred.

In relation to R12then a hydrogen atom, a fluorine atom and methyl are preferred; a hydrogen atom and a fluorine atom are particularly preferable; and a hydrogen atom is more preferred.

R13and R14each preferably represents a hydrogen atom, methyl or ethyl, and more preferably a hydrogen atom or methyl. Regarding the combination of R13and R14, preferred are combinations of: hydrogen atoms; and a hydrogen atom and methyl.

In relation to the X thiazol-2-yl, pyrimidine-2-yl, 2-pyridyl and R3R4JI- (where R3and R4have the same meanings as defined above) are the Xia preferred. Particularly preferably, when both R3and R4represent methyl.

And preferably is a group of the General formula (2).

When X is thiazol-2-yl, preferably, Y1was-N= or-CH=; Y2was-CH=, -CF= or-CCl=; R3represented a hydrogen atom, a chlorine atom or methyl; and R2was represented by methyl, ethyl or vermeil. Then, if a represents a group of General formula (2), the combination of R6and R7preferably represents a combination of: hydrogen atoms; or a hydrogen atom and methyl, and if a is a group of the General formula (3), the combination of R9and R10preferably represents a combination of: a hydrogen atom and methyl; or a hydrogen atom or cyclopropyl.

When X represents pyrimidine-2-yl, preferably, Y1was-N= or-CH=; Y2was-N=, -CH= or-CF=; R1represented a hydrogen atom, fluorine atom, chlorine atom or methyl; R2was represented by methyl, ethyl or vermeil; And a represents a group of General formula (2); and the combination of R6and R7preferably represents a combination of hydrogen atoms, methyl groups, a combination of a hydrogen atom and methyl, or a combination of a hydrogen atom and cyclopropyl.

When X is (H3C)2NCO-, it is preferable that: Y1was-N= or-CH=; Y2was-CH=, -CF= or-CCl=; R1made what was a hydrogen atom, fluorine atom, chlorine atom, iodine atom, cyano or methyl; and R2was represented by methyl or vermeil. Then, if a represents a group of General formula (2), the combination of R6and R7preferably represents a combination of: hydrogen atoms, the hydrogen atom and methyl; or a methyl group, and if a represents a group of General formula (3), the combination of R9and R10preferably represents a combination of: a hydrogen atom and methyl; hydrogen atom and methoxyethyl; or a hydrogen atom and cyanoethyl.

When Y1is-N=, then it is preferable that: X was thiazol-2-yl, pyrimidine-2-yl or (H3C)2NCO-; Y2was represented by-CH=, -CF= or-CCl=; R1represented a hydrogen atom, fluorine atom, chlorine atom, cyano or methyl; R2was represented by methyl or ethyl; a represents a group of General formula (2), and the combination of R6and R7preferably represents a combination of hydrogen atoms, methyl groups, a combination of a hydrogen atom and methyl, or a combination of a hydrogen atom and cyclopropyl.

When Y1is-CH=, then it is preferable that: X was thiazol-2-yl, pyrimidine-2-yl or (H3C)2NCO-; Y2was-N=, -CH= or-CF=; R1represented a hydrogen atom, fluorine atom, chlorine atom, iodine atom, methyl or cyano; and R2was represented by methyl or vermeil. Then, if And submitted the group of the General formula (2), the combination of R6and R7preferably represents a combination of: a hydrogen atom; a methyl group or a hydrogen atom and methyl, and if a represents a group of General formula (3), the combination of R9and R10preferably represents a combination of: a hydrogen atom and methyl; hydrogen atom and methoxyethyl; or a hydrogen atom and cyanoethyl.

When Y2is-CH=, then it is preferable that: X was thiazol-2-yl, pyrimidine-2-yl or (H3C)2NCO-; Y1was-N= or-CH=; R1represented a hydrogen atom, fluorine atom, chlorine atom, iodine atom, methyl or cyano; and R2was represented by methyl, ethyl or vermeil. Then, if a represents a group of General formula (2), the combination of R6and R7preferably represents a combination of: a hydrogen atom; a methyl group; or a hydrogen atom and methyl, and if a represents a group of General formula (3), the combination of R9and R10preferably represents a combination of: a hydrogen atom and methyl; hydrogen atom and methoxyethyl; or a hydrogen atom and cyanoethyl.

When Y2is-CF=, then it is preferable that: X was thiazol-2-yl, pyrimidine-2-yl or (H3C)2NCO-; Y1was-N= or-CH=; R1represented a hydrogen atom, a fluorine atom, a chlorine atom, or methyl; R2was represented by methyl, ethyl or vermeil; And represents what the Republican General formula (2), and the combination of R6and R7it represents a combination of hydrogen atoms; a combination of a hydrogen atom and a methyl or a hydrogen atom or cyclopropyl.

When R1represents a hydrogen atom, it is preferable that: X was thiazol-2-yl, pyrimidine-2-yl or (H3C)2NCO-; Y1was-N= or-CH=; Y2was-N=, -CH= or-CF=; and R2was represented by methyl or vermeil. Then, if a represents a group of General formula (2), the combination of R6and R7preferably represents a combination of: hydrogen atoms; or a hydrogen atom and methyl, and if a represents a group of General formula (3), the combination of R9and R10preferably represents a combination of a hydrogen atom and methyl.

When R1represents a fluorine atom, it is preferable that: X was thiazol-2-yl, pyrimidine-2-yl or (H3C)2NCO-; Y1was-N= or-CH=; Y2was-N=, -CH= or-CF=; R2presented methyl; a represents a group of General formula (2), and the combination of R6and R7it represents a combination of hydrogen atoms, methyl groups, a combination of a hydrogen atom and methyl, the combination of a hydrogen atom and cyclopropyl, the combination of a hydrogen atom and methoxyethyl or a combination of a hydrogen atom and cyanoethyl.

When R1represents a chlorine atom, it is preferable that: X who was b a thiazol-2-yl, pyrimidine-2-yl or (H3C)2NCO-; Y1was-N= or-CH=; Y2was represented by-CH= or-CF=; and R2was represented by methyl or trifluoromethyl. Then, if a represents a group of General formula (2), the combination of R6and R7preferably represents a combination of: a methyl group or a hydrogen atom and methyl, and if a represents a group of General formula (3), the combination of R9and R10preferably represents a combination of: a hydrogen atom and methyl; hydrogen atom and methoxyethyl; or a hydrogen atom and cyanoethyl.

When R1represents methyl, preferably: X was thiazol-2-yl, pyrimidine-2-yl or (H3C)2NCO-; Y1was-N= or-CH=; Y2was represented by-CH=, -CF= or-CCl=; R2was represented by methyl, ethyl or trifluoromethyl; a represents a group of General formula (2), and the combination of R6and R7it represents a combination of a hydrogen atom and methyl.

When R2represents methyl, preferably: X was thiazol-2-yl, pyrimidine-2-yl or (H3C)2NCO-; Y1was-N= or-CH=; Y2was-N=, -CH=, -CF= or-CCl=; and R1represented a hydrogen atom, fluorine atom, chlorine atom, iodine atom, methyl or cyano. Then, if a represents a group of General formula (2), the combination of R6and R7preferably represents a combination of the atoms of water the ode; methyl group; a hydrogen atom and methyl; or a hydrogen atom and cyclopropyl, and if a represents a group of General formula (3), the combination of R9and R10preferably represents a combination of: a hydrogen atom and methyl; hydrogen atom and methoxyethyl; or a hydrogen atom and cyanoethyl.

When R2represents ethyl, preferably: X was thiazol-2-yl or pyrimidine-2-yl; Y1was-N=; Y2was-CF=; R1presented methyl; a represents a group of General formula (2); and the combination of R6and R7it represents a combination of a hydrogen atom and methyl.

When R2is vermeil, it is preferable that: X was thiazol-2-yl, pyrimidine-2-yl or (H3C)2NCO-; Y1was-N= or-CH=; Y2was-N=, -CH= or-CF=; R1represented a hydrogen atom, a fluorine atom, a chlorine atom, or methyl; a represents a group of General formula (2); and the combination of R6and R7it represents a combination of a hydrogen atom and methyl.

When the combination of R6and R7it represents a combination of hydrogen atoms, it is preferable that: X was thiazol-2-yl, pyrimidine-2-yl or (H3C)2NCO-; Y1was-N= or-CH=; Y2was-N=, -CH= or-CF=; R1represented a hydrogen atom, fluorine atom, chlorine atom or iodine atom; and R2was represented by methyl, fluorine is ethyl or ethyl.

When the combination of R6and R7it represents a combination of methyl groups, preferably: X was thiazol-2-yl, pyrimidine-2-yl or (H3C)2NCO-; Y1was-N= or-CH=; Y2was-N=, -CH=, -CF= or-CCl=; R1represented a hydrogen atom, fluorine atom, chlorine atom or methyl; and R2was represented by methyl, vermeil or ethyl.

When the combination of R6and R7it represents a combination of a hydrogen atom and methyl, preferably: X was thiazol-2-yl, pyrimidine-2-yl or (H3C)2NCO-; Y1was-N= or-CH=; Y2was-N=, -CH=, -CF= or-CCl=; R1represented a hydrogen atom, fluorine atom, chlorine atom, iodine atom, methyl or cyano; and R2was represented by methyl, ethyl or vermeil.

When the combination of R9and R10it represents a combination of a hydrogen atom and methyl, preferably: X was thiazol-2-yl, pyrimidine-2-yl or (H3C)2NCO-; Y1was-N= or-CH=; Y2was represented by-CH= or-CF=; R1represented a hydrogen atom or a chlorine atom; and R2was represented by methyl.

As preferred examples of compounds of General formula (11), preferably the General formula (1), or its pharmaceutically acceptable salt, can lead, for example:

3-{3-(aminosulfonyl)aminobenzyl}-4-methyl-2-oxo-2H-1-benzopyran-7-silt EF the R dimethylcarbinol acid,

3-{3-(aminosulfonyl)aminobenzyl}-6-fluoro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-{3-(aminosulfonyl)aminobenzyl}-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-(3-aminosulfonyl-2-terbisil)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-{2-fluoro-3-(aminosulfonyl)aminobenzyl}-6-fluoro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-{3-(aminosulfonyl)aminobenzyl}-6-iodine-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-{3-(aminosulfonyl)aminobenzyl}-6-methyl-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-{3-(aminosulfonyl)aminobenzyl}-6-cyano-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-{3-(aminosulfonyl)aminobenzyl}-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-{3-(aminosulfonyl)aminobenzyl}-6-fluoro-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-{3-(aminosulfonyl)aminobenzyl}-6-chloro-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-(3-aminosulfonyl-2-terbisil)-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-{2-fluoro-3-(aminosulfonyl)aminobenzyl}-4-IU the Il-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-6-chloro-2-oxo-2H-1-benzopyran,

3-{2-fluoro-3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-6-methyl-2-oxo-2H-1-benzopyran,

3-{2-chloro-3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

4-methyl-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

6-fluoro-4-methyl-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-(3-(N-methylsulfonyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-(3-methylmonoethanolamine-2-terbisil)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

6-fluoro-4-methyl-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

6-iodine-4-methyl-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

6-methyl-4-methyl-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

6-cyano-4-methyl-3-{3-(methylaminomethyl)aminoven the yl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

4-methyl-3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

4-methyl-3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-6-fluoro-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

4-methyl-3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-6-chloro-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

4-methyl-3-{6-(methylaminomethyl)aminopyridine-2-ylmethyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

4-methyl-3-{6-(methylaminomethyl)aminopyridine-2-ylmethyl}-6-fluoro-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

4-methyl-3-{6-(methylaminomethyl)aminopyridine-2-ylmethyl}-6-chloro-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-(3-methylmonoethanolamine-2-terbisil)-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-(3-methylaminoanthraquinone)-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-(3-methylaminoanthraquinone)-6-fluoro-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

6-chloro-4-vermeil-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-(3-methylmonoethanolamine-2-terbisil)-4-vermeil-2-ox is-2N-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-6-fluoro-2-oxo-2H-1-benzopyran,

3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-vermeil-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-6-chloro-2-oxo-2H-1-benzopyran,

3-{3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-6-chloro-2-oxo-2H-1-benzopyran,

3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-6-methyl-2-oxo-2H-1-benzopyran,

6-chloro-4-methyl-3-{3-(dimethylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-{2-fluoro-3-(dimethylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-(3-(N-(2-cyanoethyl)sulfamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-(3-(N-(2-hydroxyethyl)sulfamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-ILO is first aired dimethylcarbinol acid,

3-(3-(N-(2-methoxyethyl)sulfamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-(3-(N-(2-amino-ethyl)sulfamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-(3-(N-(N'-methyl-2-amino-ethyl)methylcarbamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid hydrochloride

3-(3-(N-2,2,2-triftormetilfullerenov)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-(3-(N-methoxymethanol)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-(3-carbamoyltransferase)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-(3-methylcarbamoylmethyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

2-{2-fluoro-3-[4-methyl-2-oxo-7-(pyrimidine-2-yloxy)-2H-1-benzopyran-3-ylmethyl]phenylsulfanyl}-N-methylacetamide,

3-(3-dimethylallyltranstransferase)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

2-{2-fluoro-3-[4-methyl-2-oxo-7-(thiazol-2-yloxy)-2H-1-benzopyran-3-ylmethyl]phenylsulfanyl}-N-methylacetamide,

3-{2-methyl-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(ethylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(isopropylaminocarbonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-fluoro-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(cyclopropanesulfonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-fluoro-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-chloro-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-ethyl-6-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(cyclopropanesulfonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(cyclopropanesulfonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-chloropyridin-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-4-methyl-6-chloro-7-(eazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(cyclopropanesulfonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-4-methyl-6-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-chloropyridin-4-ylmethyl}-4-methyl-6-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(5-ftorpirimidinu-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(4-chloropyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(2,4-dimethoxypyrimidine-6-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(benzothiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(5-bromothiazole-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(5-ftorpirimidinu-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(4-chloropyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(2,4-dimethoxypyrimidine-6-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(benzothiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(5-bromothiazole-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyrazin-2-yloxy)-2-oxo-2H-1-benzopyran and

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyridine-2-yloxy)-2-oxo-2H-1-benzopyran.

Preferred from the point of view of manifestation antitumor activity are compounds of General formula (1)in which: X is thiazol-2-yl, pyrimidine-2-yl or (H3C)2NCO-; Y1represents-CH= or-N=; Y2is-CH=, -CF= or-CCl=; Y3and Y4represent-CH=; And is-NHSO2NR60R70or-NHSO2CH2CONCH3R90(where R60and R90each independently represents a hydrogen atom or methyl, and R70is a hydrogen atom, stands or ethyl (where ethyl may be optionally substituted by a Deputy selected from methoxy and cyano); R1represents a hydrogen atom, fluorine atom, chlorine atom, iodine atom, methyl or cyano; and R2is-CH3, -CH2F or-CH2CH3.

As examples of compounds which is preferred from the point of view of manifestation of antitumor activity, one can cite, for example:

3-(3-aminosulfonyl-2-terbisil)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimitile benovoy acid,

3-{2-fluoro-3-(aminosulfonyl)aminobenzyl}-6-fluoro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-{3-(aminosulfonyl)aminobenzyl}-6-iodine-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-{2-fluoro-3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

6-fluoro-4-methyl-3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-(3-(N-methylsulfonyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-(3-methylmonoethanolamine-2-terbisil)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

6-iodine-4-methyl-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

6-methyl-4-methyl-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

6-cyano-4-methyl-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

4-methyl-3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

4-methyl-3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-6-fluoro-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

4-methyl-3-{2-(methyl who isosulfan)aminopyridine-4-ylmethyl}-6-chloro-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-(3-methylmonoethanolamine-2-terbisil)-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

6-chloro-4-vermeil-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-fluoro-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-chloro-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-ethyl-6-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-4-methyl-6-chloro-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-4-methyl-6-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-chloropyridin-4-ylmethyl}-4-methyl-6-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

6-chloro-4-methyl-3-{3-(dimethylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt the ether dimethylcarbinol acid,

3-(3-(N-(2-cyanoethyl)sulfamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-(3-(N-(2-methoxyethyl)sulfamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,

3-(3-methylcarbamoylmethyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid and

3-(3-dimethylallyltranstransferase)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid.

Preferable from the viewpoint of system availability are compounds of General formula (1)in which: X is thiazol-2-yl or pyrimidine-2-yl; Y1represents-CH= or-N=; Y2represents-CH= or-CF=; Y3and Y4represent-CH=; And is-NHSO2NR60or-NHSO2CH2CONCH3(where R60represents a hydrogen atom or methyl); R1represents a hydrogen atom, fluorine atom or methyl; and R2is-CH3or-CH2F.

As examples of compounds are preferable from the viewpoint of system availability that can result, for example:

3-{2-fluoro-3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

4-methyl-3-{6-(methylaminomethyl)aminopyridine-2-ylmethyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol to the slots,

3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-6-fluoro-2-oxo-2H-1-benzopyran,

3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-vermeil-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-6-chloro-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-6-methyl-2-oxo-2H-1-benzopyran and

3-{2-fluoro-3-[4-methyl-2-oxo-7-(thiazol-2-yloxy)-2H-1-benzopyran-3-ylmethyl]phenylsulfanyl}-N-methylacetamide.

There are also compounds other than the compounds of General formula (11), which are similar to compounds of General formula (11) possess high anti-tumor activity and are suitable for use as medicines for the treatment of cell proliferative disorders, in particular cancer.

As examples of such compounds include compounds having a structure similar to the compounds of General formula (11), except that instead of incomplete patterns:

they have the structure below:

Also may be mentioned compounds having a structure similar to the compounds of General formula (11), except that instead of incomplete patterns:

they have the structure below:

Also may be mentioned compounds having a structure similar to the compounds of General formula (11), except that instead of incomplete patterns:

they have the structure below:

where combinations of G9, Z7, Z8, G1and G3have the meanings given in the table below.

where combinations of G9, Z5, Z6, G1and G2have the meanings given in the table below.

where combinations of G9, Z11, Z12, G1and G3have the meanings given in the table below.

where combinations of G9, Z9, Z10, G1and G2who have values, shown in the table below.

And may be selected from groups of the General formulas (2) and (3)above, as well as from groups of the following formulas:

where * represents the position at which the associated G6.

When a represents a group of General formula (2), R7may form a cycle together with the ring atoms G6. As specific examples of incomplete structures formed in this case, can result in a partial structure of the following formula:

where * represents the position at which the associated G7.

Specifically, you can include the following incomplete patterns:

where * represents the position at which the associated G7and the combination of Y1, Y3, Y4and Z2have the meanings given in the table below.

where * represents the position at which the associated G7and the combination of Y1, Y3, Y4and Z1have the meanings given in the table below.

As specific examples of compounds of General formula (11) include compounds of the following formula:

where is combinatii G 9, Y1, Y2, Y3, Y4, G1, G2, G3, NR6R7, G7and R2have the meanings given in the table below.

or

where combinations of G9, Z13, Z14, Z15, G1, G2, G3, NR6R7, G7and R2have the meanings given in the table below.

Below you will find examples of methods for obtaining the compounds or salts of the present invention. In each of the ways to get below the order of the stages, if necessary, can be changed. In addition, in the case when reacting connection at some stage is subjected to unwanted chemical transformation under reaction conditions stage, the method of obtaining can be carried out, for example, when protecting and Unprotecting for functional groups. When choosing a protective group and how to protect and unprotect is possible to apply, for example, by T.W. Greene, P.G.M. Wuts, Protective Groups in Organic Synthesis, Second Edition, John Wiley and Sons, Inc., New York, 1991.

X, Y1, Y2, Y3, Y4, R1, R5, R6, R7, R8, R9and R10have the meanings given to you is e, while Hal represents a halogen atom; Randis1-6alkyl (C1-6the alkyl can be substituted by the Deputy selected from the group consisting of a fluorine atom, optionally protected hydroxyl group, optionally protected carbonyl group and optionally protected carboxyl group); Rbrepresents a leaving group such as halogen atom or 2-oxazolidinone-3-yl; Rwithis a protective group for carboxyl group, such as1-4alkyl; Rdand Rwithare the same or different, and each independently or together represents a protective group for amino group; Rfis1-4alkyl; Rgrepresents a hydroxyl group or a halogen atom; Rhis a methyl group, or RcOCO-; Rirepresents a hydrogen atom or a C1-5alkyl; and represents a nitro-group, or-NRdRe.

General method-1

General method-1 is an example of a particularly preferred method of obtaining compounds of General formula (1)in which R2is Randand Y1and Y2are the same or different and each represents-CR11=.

Chemical formula 4

Stage 1-1:

Compound 1C can be obtained condenser is her deprotonated forms of the compounds 1b, which is obtained by the interaction of compound 1b with base and compounds 1A.

In relation to the base, we can mention, for example, sodium hydride, potassium hydride, hexamethyldisilazide lithium (also referred to in this document as "LiHMDS"), and the like, among which preferred is sodium hydride and the like.

In relation to the solvent for the reaction, it is possible to mention: the solvents belonging to the simple ethers such as tetrahydrofuran (also referred to in this document as "THF") and diethyl ether; and chlorinated solvents such as methylene chloride, among which THF is preferred.

The reaction temperature can be respectively determined depending on the type of solvent for the reaction, and the like, while for the interaction of compounds 1b and grounds it in General ranges from -20°C to 25°C, preferably from 0°C to 10°C, and for condensing deprotonated forms and compounds 1A it is in the range from 0°C to 60°C, preferably from 15°C to 35°C.

The reaction time can be respectively determined depending on the reaction temperature and the like, while for the interaction of compounds 1b and the base it is, in General, ranges from 10 min to 3 h, preferably from 20 min to 1 h, and for condensing deprotonated forms and compounds 1A it, about what to eat, is in the range from 2 h to 20 h, preferably from 5 hours to 15 hours

In relation to the way deprotonated forms and compounds 1A, it is preferable to add dropwise a solution containing deprotonirovannoi form to the solution containing the compound 1A.

Stage 1-2:

Compound 1 can be obtained by the interaction of compounds 1C and 1d connection in the presence of acid.

In relation to acid, we can mention: a Lewis acid such as zirconium chloride, samarium chloride (II) and aluminium chloride; inorganic acids such as sulfuric acid; and acidic resins, such as zeolite, among which preferred is sulfuric acid.

In relation to the solvent for the reaction, it is possible to use inert reaction solvents, while conditions without solvents are preferred. In that case, when using sulfuric acid, the number of equivalents in General ranges from 1 to 5, preferably from 1 to 3, relative to the compound 1d.

The reaction temperature in General ranges from -20°C to 50°C, preferably from -10°C. to 30°C.

The reaction time can be respectively determined depending on the reaction temperature and the like, while in General it ranges from 2 h to 20 h, preferably from 5 hours to 16 hours

Stage 1-3:

Compound 1g you can get vzaimode esteem compound 1E and compound 1f in the presence of a base.

In relation to the base, we can mention, for example: weakly basic inorganic salts such as sodium carbonate, potassium carbonate and cesium carbonate; and metal hydrides such as sodium hydride and potassium hydride, among which potassium carbonate, cesium carbonate and sodium hydride are preferred.

In relation to the solvent for the reaction, it is possible to mention: the solvents belonging to the simple ethers such as tetrahydrofuran and diethyl ether; and N,N-dimethylformamide and the like, among which tetrahydrofuran and N,N-dimethylformamide are preferred.

The temperature of the reaction mixture can be respectively determined depending on the type of solvent for the reaction, and the like, while when X represents a heteroaryl group with a lack of electrons, such as pyridyl or pyrimidyl, as a rule, she is from 60°C to 150°C, preferably from 70°C to 100°C; when X represents a heteroaryl group, rich in electrons, such as thiazolyl, as a rule, it is from 90°C to 200°C, preferably from 100°C to 120°C; and when X represents a group of formula R3R4NCO-, then, as a rule, it is from 0°C to 50°C, preferably from 0°C. to 30°C.

The reaction time can accordingly be determined in dependence on the temperature is eacli and the like, while, in General, it ranges from 30 min to 5 h, preferably from 40 minutes to 2 hours

In addition, when X represents a heteroaryl group, rich in electrons, such as thiazolyl, it is preferable to conduct the reaction under irradiation with microwaves in the presence of monovalent salt of copper, such as copper iodide (I), CuPF6or Cu(I)OTf (triftorbyenzola copper (I)), it is preferable that the copper iodide (I), or the like.

Stage 1-4:

Compound 1h can be obtained by reduction of compound 1g.

In respect of the reducing agent, there can be mentioned tin chloride (II), zinc and the like, among which the chloride tin (II) is preferred.

In relation to the solvent for the reaction, it is possible to mention: solvents related to alcohols, such as methanol and ethanol; solvents related to the acetic acid esters, such as ethyl acetate, n-propyl and n-butyl acetate; and mixtures thereof, among which ethyl acetate and a mixture of ethanol and ethyl acetate are preferred.

The reaction temperature generally ranges from 50°C to 150°C, preferably from 60°C. to 90°C.

The reaction time is, in General, is in the range from 30 min to 5 h, preferably from 1 hour to 3 hours

Compound 1h can also be obtained by subjecting the interaction of compound 1A according to stages 1-4, stage 1-1, phase 1-2 and phases 1-3 in that order silt is based upon the interaction of compound 1C according to the stage of 1-4, phase 1-2 and phases 1-3 in that order.

In addition, compound 1h can also be obtained from compounds other than the compound 1g, catalytic hydrogenation using palladium on coal or the like as a catalyst, as described in "Bioorganic and Medicinal Chemistry Letters, 2004, 14, 2411-2415.

Stage 1-5:

Compound 1j can be obtained by the interaction of the compounds 1h and connections 1i.

In relation to the solvent for the reaction, there may be mentioned methylene chloride, acetonitrile, N,N-dimethylformamide and the like, among which, from the viewpoint of the solubility of the compounds 1h, acetonitrile, N,N-dimethylformamide and the like are preferred.

The reaction temperature usually ranges from 15°C to 120°C, preferably from 20°C to 85°C.

The reaction time is, in General, is in the range from 1 h to 2 days, preferably 2 hours to 24 hours

In addition, it is preferable to conduct the reaction in the presence of a base. As bases are preferred organic amines, such as pyridine, triethylamine and diisopropylethylamine.

Stage 1-6:

Connection 1m can be obtained by the interaction of the compounds with 1h compound 1l in the presence of a base and then the Rc transformation in the hydrogen atom by removing protection.

When interacting with the connection 1l as reasons can be mentioned organic amines, still is as pyridine, the triethylamine and diisopropylethylamine, including diisopropylethylamine and the like is preferred.

In relation to the solvent for the reaction, there may be mentioned solvents ordinary ethers, such as diethyl ether, THF and dioxane, among which THF is preferred.

The reaction temperature is usually from 10°C to 50°C, preferably from 15°C. to 40°C.

The reaction time usually ranges from 20 min to 2 h, preferably from 30 min to 1 hour

In respect to the manner of removing the protection, it is preferred hydrolysis in the presence of a base.

In relation to the base, there can be mentioned metal hydroxides such as sodium hydroxide and potassium hydroxide, among which sodium hydroxide and the like is preferred.

In relation to the solvent for the reaction, it is possible to mention: solvents related to alcohols, such as methanol, ethanol and n-propanol; water; and mixtures thereof, among which preferred is a mixture of water and methanol.

The reaction temperature and reaction time are the same as those for connection 1l.

Stage 1-8:

Compound 1 can be obtained by condensation of compound 1m and 1n connection.

In respect of the condensing reagent, it is possible to mention dicyclohexylcarbodiimide, carbonyldiimidazole, 1-ethyl-3-(3-d is methylaminopropyl)carbodiimide and the like, among which 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and the like is preferred. In addition, it is preferable to carry out the condensation in the presence of active tarifitsiruemih reagent, such as N-hydroxysuccinimide, N-hydroxybenzotriazole or 3-hydroxy-3,4-dihydro-4-oxo-1,2,3-benzotriazol (preferably 3-hydroxy-3,4-dihydro-4-oxo-1,2,3-benzotriazole or the like).

In relation to the solvent for the reaction, it is possible to mention: the solvents belonging to the simple ethers such as diethyl ether, THF and dimethoxyethane; halogenated solvents such as methylene chloride, chloroform and carbon tetrachloride; and N,N-dimethylformamide, acetonitrile and the like, among which preferred is N,N-dimethylformamide.

The reaction temperature is usually from 10°C to 50°C, preferably from 15°C. to 40°C.

The reaction time generally ranges from 5 to 40 hours, preferably 10 minutes to 25 hours

Stage 1-7 and stage 1-9:

Compound 1K and compound 1 can be obtained by introduction1-6alkyl groups in the compound 1j and connection 1o as necessary.

Introduction1-6alkyl groups can be, for example, methods described in "Bioorganic and Medicinal Chemistry, 2005, 13, 1393-1402, "Organic Preparations and Procedures International 2004, 36, 347-351 and the "Journal of Medicinal Chemistry 2004, 47, 6447-6450.

Connected the e 1K you can also get subjecting the interaction of compound 1h according to the stage 1-7 and the stages 1-5 in that order. Compound 1 can also be obtained by subjecting the interaction of compound 1h according to the stage 1-9, stages 1-6 and stage 1-8 in that order.

Compound 1b is industrially available and can be obtained, for example, the methods described in the usual guidelines for organic chemistry (e.g., Jerry March, WILEY INTERSCIENCE Advanced Organic Chemistry 4thedition). Compound 1d is industrially available and can be obtained, for example, the methods described in Journal of Fluorine Chemistry", 2003, 120, and 173-183 "Journal of Organic Chemistry 1986, 51, 3242-3244.

General method-2

General method-2 is an example of a method of obtaining compounds 1A according to the General method 1.

Chemical formula 5

Stage 2-1:

Compound 1A can be obtained by halogenoalkanes, preferably by bromirovanii, compounds 2A.

In respect of halogenation reagent, there can be mentioned N-bromosuccinimide, N-chlorosuccinimide, N-jodatime and the like, among which N-bromosuccinimide is preferred.

As solvent for the reaction, an inert non-polar solvents such as carbon tetrachloride, are preferred.

The reaction temperature usually ranges from 20°C to 100°C, preferably from 50°C. to 90°C.

The time re the options typically range from 30 min to 10 h, preferably from 1 h to 7 h

Stage 2-2:

Compound 2C can be obtained by reduction of compound 2b.

In respect of the reducing agent, it is possible to mention alumoweld lithium hydride diisobutylaluminum (also referred to in this document as "DIBAH"), and the like, among which DIBAH is preferred.

In relation to the solvent for the reaction, it is possible to mention: the solvents belonging to the simple ethers such as diethyl ether and THF; solvents related to benzene, such as benzene, toluene and xylene, among which, in the case when the reductant used DIBAH, the preferred is toluene and the like.

The reaction temperature usually ranges from -100°C to 10°C, preferably from -85°C to 0°C.

The reaction time is, in General, is in the range from 10 minutes to 3 hours, preferably from 30 minutes to 2 hours

Compound 2C can also be obtained by conversion of the group RcOCO - 2b in connection formyl group, and the interaction of the compounds obtained according to stage 2-2.

Stage 2-3:

Compound 1A can be obtained by conversion of the hydroxyl group of compound 2C in halogen atom, preferably a bromine atom.

In respect of halogenation reagent, it is possible to mention TRIFLUORIDE diethylaminoethyl (also referred to in this document as "DAST"), thionyl the reed, tribromide phosphorus, a combination of triphenylphosphine and iodine, and the combination of the acid chloride paratoluenesulfonyl acid and sodium iodide, among which tribromide phosphorus is preferred.

In relation to the solvent for the reaction, there may be mentioned solvents ordinary ethers, such as diethyl ether, THF and dioxane, among which diethyl ether is preferred.

The reaction temperature usually ranges from -10°C to 10°C, preferably from -5°C to 5°C.

The reaction time is, in General, is in the range from 10 min to 1 h, preferably from 20 minutes to 40 minutes

Compound 2A and compound 2b are industrially available and may be obtained, for example, the methods described in the usual guidelines for organic chemistry (e.g., Jerry March, WILEY INTERSCIENCE Advanced Organic Chemistry 4thedition). Compound 2b can also be obtained, for example, by holding one of the following reactions (i)-(iii) in respect of the corresponding halogenated aryl compounds (i.e. compounds obtained by substitution of the group-COORcin connection 2b is a halogen atom): (i) the conversion of the halogen atom in the carboxyl group; (ii) the interaction of halogenated compounds with copper cyanide (I) in sulfuric acid ("Journal of Antibiotics" 1994, 47, 1456-1465; "Liebigs Annalen Chemie" 1979, 4, 554-563); and (iii) the introduction of carbon monoxide into the position in which SV is Zan halogen atom, with the use of palladium catalyst ("Journal of Organic Chemistry 1999, 64, 6921-6923).

General method 3

General method-3 is an example of a particularly preferred method for obtaining compounds 2a and 2b according to the General method 2, where Y2is-CF=.

Chemical formula 6

Stage 3-1:

Compound 3b can be obtained by the interaction of the compound 3A (in which Hal is preferably chlorine atom) with a fluorinating reagent, such as sodium fluoride, potassium fluoride and cesium fluoride (preferably cesium fluoride). If necessary, you can add a Quaternary ammonium salt, such as chloride of Tetramethylammonium.

In relation to the solvent for the reaction, preferred are dimethyl sulfoxide, sulfolan and N,N-dimethylformamide.

The reaction temperature usually ranges from 100°C to 200°C, preferably from 120°C to 160°C.

In those cases where Rhrepresents a methyl group, the reaction time generally ranges from 5 h to 20 h, preferably from 7 h to 15 h; and when Rhis RcOCO-, the reaction time is usually from 20 min to 2 h, preferably from 30 min to 1 hour

Compound 3b, in particular the compound in which Y1, Y3and Y4each represents-CH=, is a new connection and it is suitable as synthetic is anybody intermediate for compounds of General formula (1).

Compound 3A is industrially available and can be obtained, for example, methods described in Yakugaku Zasshi 1955, 75, 292-296, and in the usual guidelines for organic chemistry (e.g., Jerry March, WILEY INTERSCIENCE Advanced Organic Chemistry 4thedition).

General method 4

General method 4 is another way of obtaining compounds of 1h.

Chemical formula 7

Stage 4-1:

Compound 4A can be synthesized by reduction of compound 1E. This stage can hold similar stages 1-4.

Stage 4-2:

Compound 1h can be obtained by the interaction of the compounds 4A and compound 1f in the presence of a base. This stage can hold similar stages 1-3.

A common way-5

General method 5 is another method of obtaining compounds of 1h. Using this method you can obtain compound 1h in which Y1and Y2each independently represents-N= or-CR11=.

Chemical formula 8

Stage 5-1:

Compound 5b can be obtained by protecting the amino group of compound 5A, preferably by conversion of Rdand Rein tert-butoxycarbonyl group.

In regard to the protective reagent, it is preferable Boc2O(di-tert-BUTYLCARBAMATE) and the like.

In relation to the solvent for the reaction, you can pack manute rastvoriteli, ordinary ethers, such as diethyl ether and THF, among which the THF and the like are preferred.

The reaction temperature can be respectively determined depending on the type of solvent for the reaction, and the like, while it is usually from 0°C to 90°C, preferably from 20°C. to 70°C.

The reaction time is, in General, is in the range from 2 h to 2 days, preferably from 3 hours to 20 hours

In addition, it is preferable to conduct the reaction in the presence of a reaction accelerator such as N,N-dimethylaminopyridine.

Stage 5-2:

Compound 5C can be obtained by halogenoalkanes, preferably by bromirovanii, compounds 5b.

In respect of halogenation reagent, it is possible to mention molecular chlorine, molecular bromine, molecular iodine, N-chlorosuccinimide, N-bromosuccinimide, N-jodatime and the like, among which N-bromosuccinimide is preferred. In addition, it is preferable to halogenoalkane in the presence of the initiator radical formation, such as azoisobutyronitrile or benzoyl peroxide, preferably benzoyl peroxide or the like).

In relation to the solvent for the reaction, it is possible to mention organohalogen solvents such as carbon tetrachloride and chloroform; non-polar hydrocarbon solvents such the AK cyclohexane and hexane, among which carbon tetrachloride is preferred.

The reaction temperature generally is in the range from 50°C to 100°C, preferably from 70°C to 90°C.

The reaction time is generally equal to from 1 h to 8 h, preferably from 2 h to 6 h

Stage 5-3:

Connection 5t can be obtained by the interaction of the compounds 5C with compound 1b in the presence of a base.

In relation to the base, we can mention, for example, metal hydrides such as sodium hydride, potassium hydride and LiHMDS, among which sodium hydride and the like is preferred.

In relation to the solvent for the reaction, it is possible to mention: the solvents belonging to the simple ethers such as THF and diethyl ether; and chlorinated solvents such as methylene chloride, among which THF is preferred.

The reaction temperature generally is in the range from -20°C to 25°C, preferably from 0°C. to 10°C.

The reaction time is usually from 2 h to 24 h, preferably from 6 hours to 15 hours

In addition, the connection 5t you can get condensation reactions described in international publication WO 2002/08217 with subsequent catalytic hydrogenation.

Stage 5-4:

Compound 5d can be obtained by carrying out the removing the protection of the amino group with simultaneous carrying out the condensation reaction of the compound 5t and the unity 1d in the presence of acid.

In relation to acid, we can mention: a Lewis acid such as zirconium chloride, samarium chloride (II) and aluminium chloride; inorganic acids such as sulfuric acid; and acidic resins, such as zeolite, among which preferred is sulfuric acid.

In relation to the solvent for the reaction, it is possible to use inert reaction solvents, while conditions without solvents are preferred. In that case, when using sulfuric acid, the number of equivalents, typically ranges from 1 to 5, preferably from 1 to 3, relative to the compound 1d.

The reaction temperature generally is in the range from -20°C to 50°C, preferably from -10°C. to 30°C.

The reaction time can be respectively determined depending on the reaction temperature and the like, despite the fact that it usually takes from 2 h to 20 h, preferably from 5 hours to 16 hours

Stage 5-5:

Compound 1h can be obtained by subjecting the interaction of the 5d connection with compound 1f, in the presence of a base. This stage can hold similar stages 1-3.

Compound 5A is industrially available and can be obtained, for example, methods described in "European Journal of Medicinal Chemistry 1999, 34, 1003-1008, "Bioorganic and Medicinal Chemistry Letters 2004, 16, 1411-1416, "Bioorganic and Medicinal Chemistry Letters 2002, 12, 2109-2112, "Chemical and Pharmaceutical Bulletin 2004, 52, 818-829 the like. In addition, compound 5A, 5b and the connection can also be obtained, for example, the introduction of the nitrogen atom in the corresponding halogenated aryl compound (i.e. a compound obtained by substitution of an amino group or-NRdRein connection 5A or 5b on the halogen atom in position, which is linked halogen atom, using a palladium catalyst (Organic Letters 2002, 4, 4689-4692).

As a rule, using-1, -4, -5 and -8, compounds in which Rais1-6alkyl (C1-6alkyl substituted Deputy selected from the group consisting of optionally protected hydroxyl group, optionally protected carbonyl group and optionally protected carboxyl group) it is possible to obtain the compound of General formula (1)in which R2is1-6alkyl, substituted by a halogen atom, a transformation is not necessarily a protected hydroxyl group, optionally protected carbonyl group and optionally protected carboxyl group into a halogen atom. Turning to the fluorine atom can be performed at an appropriate stage methods-1, -4, -5 and -8 using DAST or the like as a fluorinating reagent, as described in "Synthesis", 2002, 17, 2561-2578 or the like. Becoming a chlorine atom or a bromine atom can be accomplished by using the compound 1j, connection 1o or so beneath the Noah and using thionyl chloride, PBr3or the like as a halogenation reagent, as described in Larock, "Comprehensive Organic Transformations" or the like.

A common way-6

General method 6 is an example of a preferred method of obtaining compounds of General formula (1)in which R2is1-6alkyl, substituted by a fluorine atom.

Chemical formula 9

Stage 6-1:

Compound 6b can be obtained by introduction of halogen atom, preferably bromine atom, in connection 6A.

In respect of halogenation reagent, there can be mentioned, for example, N-chlorosuccinimide, N-bromosuccinimide, N-jodatime and the like, among which N-bromosuccinimide is preferred.

In relation to the solvent for the reaction, there can be mentioned carbon tetrachloride, diethyl ether, THF and the like, among which THF or the like is preferred.

The reaction temperature generally is in the range from -50°C to 10°C, preferably from -20°C. to 5°C.

The reaction time is usually from 20 min to 2 h, preferably from 30 min to 1 hour

Stage 6-2:

Compound 6C can be obtained by further substitution of the halogen atom in the compound 6b on the fluorine atom.

In respect of the fluorinating reagent, it is possible to mention ftorida metals, such as potassium fluoride and fluoride is the atrium, among which potassium fluoride is preferred. It is preferable to carry out the fluorination in the presence of a crown ether such as 18-crown-6-ether), corresponding to the metal in the metal fluoride used.

In relation to the solvent for the reaction, preferred is acetonitrile.

The reaction temperature usually ranges from 20°C to 100°C, preferably from 20°to 80°C.

The reaction time is usually from 1 h to 6 h, preferably from 1.5 hours to 5 hours

It is possible to obtain the compound of General formula (1)in which R2is1-6alkyl, substituted by a fluorine atom, unprotect compounds 6C, if necessary, and then, subjecting him to interact according to stages 1-4 stages 1-5 or stages 1-6 and subsequent stages of the common way-1.

A common way-7

General method 7 is an example of a preferred method of obtaining compounds of General formula (1)in which R2is1-6alkyl, substituted by a halogen atom.

Chemical formula 10

Stage 7-1:

Compound 7C can be obtained by subjecting the interaction deprotonirovannoi form of compound 1g, which is obtained by reaction of the compound 1g and the base, with compound 7b.

Regarding the reasons you mentioned hydride NAT the Oia, the potassium hydride, LiHMDS, and the like, among which LiHMDS is preferred.

In relation to the solvent for the reaction, it is possible to mention: the solvents belonging to the simple ethers such as THF and diethyl ether; and chlorinated solvents such as methylene chloride, among which THF is preferred.

The reaction temperature can be respectively determined depending on the type of solvent for the reaction, and the like, despite the fact that for the reaction between 1 g connection and the reason it usually ranges from -100°C to 10°C, preferably from -85°C to 5°C, and to interact deprotonated forms and compounds 7b, it is usually in the range from -5°C to 40°C, preferably from 0°C. to 30°C.

The reaction time can be respectively determined depending on the reaction temperature and the like, despite the fact that for the reaction between 1 g connection and it usually ranges from 20 minutes to 3 hours, preferably from 30 min to 1.5 h, and to interact deprotonated forms and compounds 7b, it is usually in the range from 20 minutes to 20 hours, preferably from 30 minutes to 15 hours

Stage 7-3:

Compound 7f can be obtained by subjecting the interaction deprotonirovannoi form of compound 1g, which is obtained by reaction of the compound 1g and the base, with a compound 7E. This stage can hold EN is a logical stage 7-1.

Stage 7-2 and stage 7-4:

Compound 7d and the connection 7g can be obtained by restoring respectively compounds 7C and 7f. This stage can hold similar stages 1-4.

It is possible to obtain the compound of General formula (1)in which R2is1-6alkyl substituted by halogen atom, transformation connection 7d or compounds 7g manner similar to that described in General method 1.

The compound in which R2is1-6alkyl, substituted by a fluorine atom, can also be obtained by transformation of the introduced hydroxy or carbonyl group in the compound 7C or 7f in the fluorine atom, and then, subjecting him to interact according to stages 1-4 and subsequent stages of the General method 1. The conversion of hydroxy or carbonyl group in the fluorine atom can be done using the DAST or the like as a fluorinating reagent, as described in "Synthesis", 2002, 17, 2561-2578 or the like.

General method-8

General method-8 is another method of obtaining compounds of 5t and an example of a particularly preferred method of obtaining compounds of General formula (1)in which Y1represents-N=.

where Rjrepresents a leaving group such as halogen atom, a C1-4alkoxy or di(C1-4)amino group or a hydrogen atom; and Rkis a leaving group, such to the to the atomic charges, tripterocalyx, methansulfonate, paratoluenesulfonyl or halogen atom.

Stage 8-1:

Compound 8b can be obtained by subjecting the interaction deprotonirovannoi form compounds 8A, which is obtained by the reaction of compounds 8A and a strong base, with a compound of General formula: RjSNO (below also refer simply to "RjSNO").

Against a strong Foundation, we can mention: amides of metals, such as hexamethyldisilazide lithium and diisopropylamide lithium; altimetry, such as utility and utility; and the halide alkylamine and the like, among which hexamethyldisilazide lithium, diisopropylamide lithium and the like are preferred. In relation to RjSNO, we can mention: derivatives of formic acid, such as foreshore and esters of formic acid; formamide, such as N,N-dimethylformamide (also applies to "DMF"), N, N-diethylformamide, among which DMF is preferred. When using formaldehyde as RjSNO is possible to obtain a connection 8s directly from compound 8A without obtaining connection 8b.

In relation to the solvent for the reaction, it is possible to mention: the solvents belonging to the simple ethers such as THF and diethyl ether; and chlorinated solvents such as methylene chloride and chetyrehhloristy the initial carbon among which THF is preferred.

The reaction temperature can be respectively determined depending on the type of solvent for the reaction, and the like, despite the fact that in the interaction of compounds 8A and a strong base, it usually ranges from -100°C to 25°C, preferably in the range from -95°C to -65°C, and the interaction deprotonated form and RjSNO she usually equals -100°C to 35°C, preferably in the range from -30°C to 10°C.

The reaction time can be respectively determined depending on the reaction temperature and the like, despite the fact that in the interaction of compounds 8A and a strong base, it is usually from 10 min to 10 h, preferably in the range from 20 min to 5 h, and the interaction deprotonated form and RjSNO it, as a rule, is equal to from 30 minutes to 40 hours, preferably in the range from 30 minutes to 4 hours

Stage 8-2:

Compound 8C can be obtained by the interaction between the compound 8b and a reducing agent.

In respect of the reducing agent, it is possible to mention complex compounds of metal-hydrogen (for example, borhydride metals, such as sodium borohydride, sulfated sodium borohydride, cyanoborohydride sodium, trimethoxyborohydride sodium, lithium borohydride, cyanoborohydride lithium, triethylborohydride lithium tri-secondary-butylbromide lithium, three-Tr is t-butylbromide lithium the calcium borohydride, potassium borohydride, triisopropoxide potassium Tris-secondary-butylbromide potassium, zinc borohydride and triacetoxyborohydride sodium; and alumoweld metals, such as alumalite lithium, trimethoxyborohydride lithium tri-tert-butoxylated lithium, alumoweld lithium/trichloramine, alumoweld lithium/boron TRIFLUORIDE, alumoweld charmagne, alumoweld magnesium, alumoweld sodium, triaxiality sodium bis(methoxyethoxy)alumoweld sodium, among which borhydride metals, such as sodium borohydride are preferred.

In relation to the solvent for the reaction, it is possible to mention: the solvents belonging to the simple ethers such as THF and diethyl ether; chlorinated solvents such as methylene chloride and carbon tetrachloride; and solvents related to alcohols, such as methanol and ethanol; among which THF is preferred.

The reaction temperature can be respectively determined depending on the type of solvent for the reaction, and the like, despite the fact that, typically, it ranges from -100°C to 100°C, preferably from -10°C to 50°C.

The reaction time can be respectively determined depending on the reaction temperature and the like, while it usually is in the range from 10 min to 30 h, preferably from 1 h to 8 is.

Stage 8-3:

Compound 8d can be obtained by the interaction between the compound 8C and aminimum reagent.

In relation amineralo reagent, it is possible to mention: ammonia; aqueous ammonia; ammonium salts such as ammonium chloride and ammonium acetate; amides of metals, such as hexamethyldisilazide lithium hexamethyldisilazide potassium, hexamethyldisilazide sodium, lithium amides, amides of sodium and potassium amides; and silazane, such as hexamethyldisilazane, among which ammonia and amides of metals, such as hexamethyldisilazide lithium are preferred.

In the case when minimumage of ammonia reagent is used, the reaction can be carried out in the presence of an organic amine, such as triethylamine, bases such as sodium hydroxide, or the like. As minimumage reagent use metal amide, such as hexamethyldisilazide lithium, the reaction can be carried out in the presence of palladium catalyst and phosphine ligand, which can be used at the stage 8-5.

As solvent for the reaction can be mentioned: hydrocarbon solvents such as toluene and benzene; solvents ordinary ethers, such as THF, diethyl ether and dioxane; chlorinated solvents such as methylene chloride; and nephratonia solvents, such as DMF; among which is olwal, DMF and dioxane are particularly preferred.

The reaction temperature can be respectively determined depending on the type of solvent for the reaction, and the like, despite the fact that, as a rule, it is in the range from 0°C to 200°C, preferably from 30°to 150°C.

The reaction time can be respectively determined depending on the reaction temperature and the like, despite the fact that it is usually from 1 hour to 30 hours, preferably 2 hours to 10 hours

Compound 8d can also be obtained by protection of the hydroxyl group in compound 8C, and then subjecting the interaction of the compound according to this stage, and then removing the protection of the hydroxyl group.

When choosing a protective group and how to protect and unprotect, you can refer to, for example, T. W. Greene, P. G. M. Wuts, "Protective Groups in Organic Synthesis", Second Edition, John Wiley and Sons, Inc., New York, 1991. As preferred examples of the protective group, you can specify: tizanidine silyl groups such as trimethylsilyl, citycell, diisopropylzinc, dimethylazobenzene, diethylenediamine, dimethylhexylamine, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, tribenzylamine, three-p-silisili, triphenylsilane, diphenylmethylsilane and tert-butylmethacrylate; and substituted benzyl groups such as benzyl, triphenylmethyl, 2,4,6-trimethylbenzyl, p-bromobenzyl, o-nitrobenzyl, p-neath benzyl, p-methoxybenzyl and 2,6-dimethoxybenzyl, among which the tert-butyldimethylsilyl (also belongs to the group of "TBS") is preferred.

In that case, when the protective group is tizamidine silyl, protection of the hydroxyl group can be conducted by subjecting compound 8C interaction with trisemester similaroriginal in the presence of a base.

In relation to the base, it may be mentioned amines such as triethylamine, pyridine, imidazole, triazole, benzimidazole and benzotriazole, among which preferred is imidazole.

In respect of the halide, it is possible to specify the chloride, bromide and iodide, of which the chloride is preferred.

In relation to the solvent for the reaction, there may be mentioned solvents related to Amida, such as N,N-dimethylacetamide, N,N-diethylmetatoluamide (also applies to "DMI"), and DMF, among which DMF is preferred.

The reaction temperature can be respectively determined depending on the type of solvent for the reaction, and the like, despite the fact that, as a rule, it is in the range from 0°C to 150°C, preferably from 15°C to 65°C.

The reaction time can be respectively determined depending on the reaction temperature and the like, while it is usually from 30 minutes to 30 hours, preferably from 1 h to 5 h

When a protective group which is tizamidine silyl, the unprotect a protected hydroxyl group in the compound 8d you can spend, for example, subjecting compound interaction with acid and fluoride.

In relation acid, may be mentioned inorganic acids such as hydrochloric acid, Hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, Perlina acid; and organic acids such as triperoxonane acid, trichloroacetic acid, methanesulfonate acid, p-toluensulfonate acid, benzolsulfonat acid, camphorsulfonic acid, oxalic acid and citric acid; and optionally, you can specify an acidic ion-exchange resin.

In relation to fluoride, it is possible to mention fluoride, Tetra-n-butylamine, hydrogen fluoride/pyridine, hydrogen fluoride/triethylamine, hydrofluoric acid, lithium fluoride, sodium fluoride, potassium fluoride, cesium fluoride and the like, among which the fluoride, Tetra-n-butylamine and the like is preferred.

The solvent for the reaction can respectively be defined and can be used, for example: solvents related to alcohols; solvents related to the simple ethers such as THF and diethyl ether; solvents that are related to esters, such as ethyl acetate and methyl acetate; solvent-related NITRILES, such as acetonic is l, benzonitrile and benzylcyanide; and solvents, related to Amida, such as N,N-dimethylacetamide, DMI and DMF, among which the solvent-ethers, such as THF, are preferred.

The reaction temperature can be respectively determined depending on the type of solvent for the reaction, and the like, despite the fact that, as a rule, it is in the range from 0°C to 150°C, preferably from 15°C to 65°C.

The reaction time can be respectively determined depending on the reaction temperature and the like, while it is usually from 5 minutes to 30 hours, preferably 10 minutes to 3 hours

Stage 8-4:

Compound 8E can be obtained by protecting the amino group in compound 8d.

With respect to the method of protecting an amino group, you can indicate the methods, in the formulation which are various protective groups, mainly used in organic chemistry, while preferred are, for example: method of formation of carbamate using tert-butoxycarbonyl or the like, the method of formation of imine using phenylmethylene, diphenylmethylene or the like and method of education amide by acetylation, triptoreline or the like, and particularly preferred are: method of formation of carbamate using tert-butoxycarbonyl or that p is such and the method of formation of imine using diphenylmethylene or the like.

The method of formation of carbamate can be performed similarly as described for stage 5-1.

Method of imine formation can be carried out by heating compound 8d with an aldehyde, such as benzaldehyde or ketone, such as benzophenone.

In relation to the solvent for the reaction, the preferred solvents are related to alcohol, such as methanol, ethanol, n-propanol and isopropanol, and methanol is particularly preferred.

The reaction temperature can be respectively determined depending on the type of solvent for the reaction, and the like, despite the fact that, as a rule, it is in the range from 10°C to 120°C, preferably from 40°C. to 90°C.

The reaction time can be respectively determined depending on the reaction temperature and the like, while it is usually from 30 minutes to 20 hours, preferably from 1 h to 5 h

Stage 8-5:

Compound 8E can also be obtained by subjecting compound 8C interaction with the compound of the formula: HNRdRe(below also refer simply to "HNRdRe").

Against HNRdReyou can specify, for example: acetamide, such as ndimethylacetamide and bis(trimethylsilyl)ndimethylacetamide; imine, such as diphenylamine; and aralkylamines, such as benzylamine, including ndimethylacetamide, bis(trimethylsilyl)ndimethylacetamide and diphenylamine are preferred is sustained fashion.

It is preferable to conduct the reaction in the presence of palladium catalyst and phosphine ligand for its acceleration.

As the palladium catalyst, you can specify the palladium acetate, triptorelin palladium, palladium chloride, palladium on charcoal, dimer chloride allylpalladium, tetrakis(triphenylphosphine)palladium, bis(dibenzylideneacetone)palladium, Tris(dibenzylideneacetone)palladium, adduct of Tris(dibenzylideneacetone)dipalladium-chloroform, dichlorobis(triphenylphosphine)palladium, bis(acetonitrile)dichloropalladium and the like, among which preferred are bis(dibenzylideneacetone)palladium, Tris(dibenzylideneacetone)dipalladium and the like.

In respect of the phosphine ligand, there may be mentioned triphenylphosphine, tri-o-tolylphosphino, three(2-furyl)phosphine, tri-tert-butylphosphine, tricyclohexylphosphine, tri-n-butylphosphine, 1,2-bis(diphenylphosphino)ethane, 1,3-bis(diphenylphosphino)propane, 1,4-bis(diphenylphosphino)butane, 1,1'-bis(diphenylphosphino)ferrocene, 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, DICYCLOHEXYL[2',4',6'-Tris(1-methylethyl)-1,1'-biphenyl-2-yl]phosphine (X-Phos) and the like, among which 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl and DICYCLOHEXYL[2',4',6'-Tris(1-methylethyl)-1,1'-biphenyl-2-yl]phosphine (X-Phos) are preferred.

As solvent for the reaction, mention can be made of: hydrocarbon solvents such as hexane, heptane, octane, then the Wal, benzene and xylene; solvents ordinary ethers, such as THF, diethyl ether and dioxane; and nephratonia polar solvents such as DMF and N,N-dimethylacetamide, among which aromatic hydrocarbon solvents such as toluene and benzene are preferred.

The reaction temperature can be respectively determined depending on the type of solvent for the reaction, and the like, despite the fact that, typically, it ranges from 20°C to 140°C, preferably from 45°to 80°C.

The reaction time can be respectively determined depending on the reaction temperature and the like, while it usually is in the range from 1 h to 30 h, preferably from 5 hours to 20 hours

Compound 8E can also be obtained by protection of the hydroxyl group in compound 8C, then the interaction of the compounds according to this stage and then removing the protection of the hydroxyl group. You can spend the same way as the protection of the hydroxyl group in compound 8C, then the interaction of the compounds according to the stage 8-3 and then removing the protection of the hydroxyl group in a compound 8d.

Stage 8-6:

Compound 8f can be obtained by conversion of the hydroxyl group of compound 8E in a leaving group, for example by esterification (acetylation, metilirovaniem, totalrevenue or the like) hydroxy who enoy group or substitution of a hydroxyl group on a halogen atom, preferably the esterification with the formation of the sulfonate (metilirovaniem, totalrevenue or the like) of the hydroxyl group.

The etherification of compound 8F with the formation of the sulfonate can spend the interaction of compound 8F with methanesulfonamido, para-toluensulfonate or the like in the presence of a base.

In relation to the base, we can mention, for example: metal hydrides such as sodium hydride, potassium hydride and lithium hydride; and metal alcoholate, such as tert-butyl potassium, tert-butyl sodium, tert-butyl lithium, tert-pantilat potassium tert-pantilat sodium tert-pantilat lithium, among which the metal alcoholate, such as tert-butyl lithium is preferred.

In relation to the solvent for the reaction, the solvents belonging to the simple ethers such as THF, diethyl ether and dioxane are preferred, and THF is particularly preferred.

The reaction temperature can be respectively determined depending on the type of solvent for the reaction, and the like, despite the fact that, as a rule, it is from -90°C to 30°C., preferably from -50°C to 10°C.

The reaction time can be respectively determined depending on the reaction temperature and the like, while it usually is in the range from 5 min to 10 h, preferably from 15 min to 2 hours

The esterification with the formation of acetate (acetylation, triptoreline or the like) compounds 8E can easily carry out a method commonly used in organic chemistry. For example, this reaction can be carried out by interaction of compound 8F with the corresponding galogenangidridy acid (acetylchloride, triftoratsetilatsetonom or the like) or an acid anhydride (acetic anhydride, triperoxonane anhydride or the like) in the presence of a base.

Halogenoalkane compounds 8E can be performed similarly as described for stage 2-3. In addition, it can also carry out the exchange reaction between the sulfonate obtained above esterification with the formation of sulfonate, and the anion of halogen.

Stage 8-7:

Connection 5t can be obtained by the interaction of compound 8f with compound 1b in the presence of a base. This stage can be similar to stage 5-3.

Compound 8A is industrially available and can be obtained, for example, by methods described in the usual guidelines for organic chemistry (e.g., Jerry March, WILEY INTERSCIENCE Advanced Organic Chemistry 4thedition). As Hal in connection 8A, a chlorine atom is preferred. Some examples of compounds 8b and 8C are known compounds, which are widely available.

On the basis of common methods-1-8 the examples below, or when accessed, it is also possible to synthesize, for example, the following connections:

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(aminosulfonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-chloro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-chloro-3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-methyl-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-methyl-3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-4-methyl-6-fluoro-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(aminosulfonyl)aminopyridine-4-ylmethyl}-4-methyl-6-fluoro-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-4-methyl-6-chloro-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(aminosulfonyl)aminopyridine-4-ylmethyl}-4-methyl-6-chloro-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-4-methyl-6-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(aminosulfonyl)aminopyridine-4-ylmethyl}-4-methyl-6-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(ethylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(aminosulfonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-fluoro-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(aminosulfonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-fluoro-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-chloro-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(aminosulfonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-chloro-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(aminosulfonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-chloro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-chloro-3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-methyl-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-methyl-3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-4-methyl-6-fluoro-7-(N-Mei-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(aminosulfonyl)aminopyridine-4-ylmethyl}-4-methyl-6-fluoro-7-(N-Mei-2-yloxy)2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-4-methyl-6-chloro-7-(N-Mei-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(aminosulfonyl)aminopyridine-4-ylmethyl}-4-methyl-6-chloro-7-(N-Mei-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-4-methyl-6-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(aminosulfonyl)aminopyridine-4-ylmethyl}-4-methyl-6-methyl-7-(N-Mei-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(N-Mei-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(aminosulfonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(N-Mei-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-fluoro-7-(N-Mei-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(aminosulfonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-fluoro-7-(N-Mei-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-chloro-7-(N-Mei-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(aminosulfonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-chloro-7-(N-Mei-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-methyl-7-(N-Mei-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-(aminosulfonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-methyl-7-(N-m is telemedical-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-chloro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(N-Mei-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-chloro-3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(N-Mei-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-methyl-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(N-Mei-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-methyl-3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(N-Mei-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(N-Mei-2-yloxy)-2-oxo-2H-1-benzopyran,

3-{2-fluoro-3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(N-Mei-2-yloxy)-2-oxo-2H-1-benzopyran.

The present invention includes pharmaceutically acceptable salts of the compounds of General formula (11), preferably the General formula (1). These salts is produced by interaction of the compound with an acid or a base, suitable for receiving farmacevticheskih products. Examples of salts include salts of inorganic acids, such as hydrochloride, hydrobromide, hydroiodide, sulfates and phosphates; sulfonates, such as methanesulfonate, benzosulfimide and toluensulfonate; carboxylates, such as formate, acetate, oxalate, maleate, fumarate, citrates, malaty, succinate, malonate, gluconate, mandelate, benzoate, salicylates, peracetate, triptoreline, tartratami, propionate and glutamate; alkali metal salts, such the AK lithium salts, salts of sodium, potassium, salts of cesium and rubidium salt; salts of alkaline-earth metals such as magnesium salts and calcium salts; and ammonium salts such as ammonium salts, salts of alkylamine, salts of dialkylamino, salts of trialkylamine and salts of tetraalkylammonium. Among them, preferred are alkali metal salts such as lithium salt, sodium salt, potassium salt, cesium salt and the salt of rubidium, and particularly preferred salts are sodium and potassium salts.

The compound or its pharmaceutically acceptable salt according to the present invention can be used for the treatment of cell proliferative disorders, in particular cancer, respectively, the introduction of the patient pharmaceutically effective amount of him or in the form of pharmaceutical compositions. In relation to route of administration, you can use: a systematic introduction, such as oral administration, rectal administration, intravenous administration, intramuscular administration, subcutaneous administration, intracisternally introduction, intravaginal introduction, vnutribruchinne introduction, vnutrishkolnoe introduction or inhalation introduction; or a local application in the form of an ointment, gel, cream or the like.

In the case when the compound or its pharmaceutically acceptable salt according to the present invention are used as pharmaceutical compositions, as a rule, it is we who are in some form (dosage form). In terms of dosage form, it may be mentioned, for example, tablet, capsule, granule, powder, fine granule, a pill, and aqueous or non-aqueous solution and suspension. In addition, the compound or salt can be used in various forms with controlled release and, with regard to the forms of controlled release, you can specify, for example, shape, implantirovannoi in the body, and form, applied to the mucosa of the oral or nasal cavity. The solution or suspension can be stored in a container suitable for receiving a single dose.

Various dosage forms mentioned above can be obtained in a known manner, by mixing the compounds or salts with pharmaceutically acceptable additive. In regard to supplements, we can mention the filler, a lubricating substance (coating material), a binder, baking powder, stabilizer, flavoring substance, a base, a dispersant, solvent, surfactant, emulsifier and the like.

Regarding the filler, it is possible to mention, for example, starches (starch, potato starch, corn starch and the like), lactose, crystalline cellulose and secondary acidic calcium phosphate.

As the moving substance (coating material) you can specify, for example, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose is, shellac, talc, Carnauba wax and paraffin wax.

In relation to the binder, it is possible to mention, for example, polyvinylpyrrolidone and macrogol, and the same substances can be specified as examples of the filler.

In respect of baking powder, one may mention, for example, chemically modified starches and cellulose, such as sodium salt croscarmellose, sodium salt of carboxymethyl amylum and cross-linked polyvinylpyrrolidone, as well as some substances that were listed as examples of the filler.

In respect of the stabilizer, there can be mentioned, for example: esters of peroxybenzoyl acid, such as methylparaben and propylparaben; benzalconi chloride; phenols such as phenol and cresol; thimerosal; along with dehydroacetic acid and sorbic acid.

In relation to flavoring substances, there can be mentioned, for example, sweeteners and flavouring agents, which are usually used.

Regarding the fundamentals, then you can specify, for example: fats, such as melted pork fat; vegetable oils, such as olive oil and sesame oil; higher alcohols such as stearyl alcohol and cetanol; oils of animal origin; lanolin acid; petrolatum; waxes; bentonite; glycerin and glycol oil.

In respect of baking powder, one may mention, for example, cellulose derivatives (Arabian gum, tragic novou gum, methycellulose and the like), polyesters stearic acid, sorbitan sesquioleate, aluminum monostearate, sodium alginate and esters sorbitan and fatty acids.

As a solvent or diluent in the liquid dosage form can be specified, for example, phenol, chlorocresol, purified water and distilled water.

In respect of surfactant or emulsifier, there can be mentioned, for example, Polysorbate 80, polyoxyl-40-stearate and lauromacrogol.

The preferred content of the compound or its pharmaceutically acceptable salt according to the present invention in the composition varies depending on the dosage form and typically is in the range from 0.01% to 100% by mass.

In the case when the compound or its pharmaceutically acceptable salt according to the present invention is used as a drug for the treatment of cell proliferative disorders, the dose can determine accordingly depending on the severity of the symptom, age, body mass, relative health, the presence or absence of treatment, concomitant medications, routes of administration, and the like. For example, when the subject is a warm-blooded animal, particularly a human, the dose per 1 kg of body weight per day for oral administration is preferably from 0.00001 to 5000 is g, more preferably from 0.0001 to 10 mg. Dose for parenteral administration is preferably equal to from 0.00001 to 5000 mg, more preferably from 0.0001 to 10 mg. of the above doses can be used to enter a frequency from once a day to once in 3 weeks or daily in 2-4 divided doses.

As described above, the compound or its pharmaceutically acceptable salt and a pharmaceutical composition of the present invention can be used as a drug for the treatment of cell proliferative disorders, in particular cancer. In relation to cancer, it is possible to mention malignant blood diseases and malignant diseases of the lymphatic system, such as leukemia (acute malacitana leukemia, acute lymphocytic leukemia, chronic malacitana leukemia, chronic lymphocytic leukemia, and the like), malignant lymphoma (Hodgkin's disease, non-Hodgkin's lymphoma and the like), multiple myeloma and myelodysplastic syndrome; and solid malignant tumors, such as malignant brain tumor, glioma, malignant head and neck tumors (malignant tumor of the pharynx, cancer of the larynx, cancer of the tongue, and the like), cancer of the esophagus, malignant tumor of stomach malignant about whole of the colon, rectum, malignant tumor of lung (small cell lung carcinoma, non-small cell lung carcinoma or the like), a malignant tumor of the thyroid gland, cancer of the breast, cancer of the gallbladder, cancer of the pancreas, cancer of the liver, cancer of prostate, cancer of the ovaries, cancer of uterus, cancer of the testis, cancer of the kidney, cancer of the bladder, cancer of kidney, pelvic and urinary tract, malignant melanoma and skin cancer.

As examples of the compound or its pharmaceutically acceptable salt according to the invention can be specified compounds of the following formula and their pharmaceutically acceptable salts:

where combinations of G9, Y1, Y2, Y3, Y4, G1, G2, G3, Z19, G7and R2have the meanings given in the table below.

or

where combinations of G9, Y1, Y2, Y3, Y4, Z16, Z17, Z18, G7and R2have the meanings given in the table below.

or

where combinations of G9, Z13, Z14, Z15, G1, G2, G3, Z16, G7and R2have the meanings given in the table below.

or

where combinations of G9, Y1, Y2, Y3, Y4, Z16, Z17, NR6R7, G7and R2have the meanings given in the table below.

where combinations of G9, Z23, Z24, Z25, Z21, Z22, Z26, G7and R2have the meanings given in the table below.

Given in example embodiments of the present invention will be described below more specifically based on examples (examples obtain and test examples).

Examples get

In the following examples (synthetic examples) NMR analysis was performed using a mass spectrometer JNM-EX270 (270 MHz) manufactured by JEOL, JNM-GSX400 (400 MHz) manufactured by the same manufacturer or ARX-300 (30 MHz), Bruker, data of NMR are given in ppm (parts per million, σ) and stop-signal deuterium from a sample of the solvent was used as standard.

In addition, mass spectral data were obtained using a spectrometer JMS-DX303 production or JEOL JMS-SX/SX102A production of the same manufacturer or by using a Micromass (Navigator production Finningan), equipped with a liquid chromatograph high resolution for elution with a gradient Agilent 1100 manufactured by Agilent Technologies.

When used industrially available reagents, they were used directly without pre-treatment such as distillation or recrystallization. Used solvents for reactions were anhydrous, if they are industrially available.

Basically all chemical reactions were carried out in nitrogen atmosphere.

In the sense in which the expression "solvent drove" used herein means that the solvent is kept at reduced pressure using a rotary evaporator.

In the case when the connection has been impossible to obtain with high purity using standard protocols of synthesis, if necessary, can be carried out isolation and purification by chromatography on silica, chromatography on aluminium oxide (Almagel) or the like for connection with the more high purity.

General method-1

Initially, this will be disclosed to the General method 1 described earlier.

Compound 1C-2:

Ethyl ester of 2-(2-fluoro-3-nitrobenzyl)-3-oxomalonate acid

Chemical formula 11

Ethylacetoacetate time (37.4 ml, 294 mmol) was added at 0°C. to a suspension of sodium hydride (65%, 10.8 g) in THF (600 ml) and the mixture was stirred at 0°C for 30 minutes the Mixture was added dropwise at 0°C. to a solution of 1-methyl bromide-2-fluoro-3-nitrobenzene (compound 1A-1) (68,7 g, 294 mmol) in THF (400 ml) and the reaction mixture was stirred at room temperature overnight. Then the reaction mixture was poured into 0.5 N hydrochloric acid and was extracted with ethyl acetate. The organic extract was washed with saturated salt solution and dried over magnesium sulfate. The crude product was obtained by concentration in vacuo and was purified column chromatography (mixture of ethyl acetate:hexane = 1:3) to obtain specified in the connection header (52,2 g, 63%) as a yellow oil.

1H-NMR (DMSO-d6, 270 MHz) δ (ketone body) (ppm): 8,01 (TD, J=7,6, 1.9 Hz, 1H), 7,72 (TD, J=7,2, 1.9 Hz, 1H), 7,37 (TD, J=7,5, 1.1 Hz, 1H), 4,11 (m, 1H), 4,07 (arcs, J=7,0, 1.0 Hz, 2H), and 3.16 (t, J=7,3 Hz, 2H), of 2.23 (s, 3H), 1,10 (t, J=7,0 Hz, 3H).

ESIMC*m/z: 284 (M+H).

Compound 1C-1:

Ethyl ester of 2-(3-nitrobenzyl)-3-oxomalonate acid

Chemical formula 12

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1C-2, except that 1-methyl bromide-3-nitrobenzene was used instead of 1-methyl bromide-2-fluoro-3-nitrobenzene.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 1,08 (3H, t, J=6,8 Hz in), 2.25 (3H, s), 3, 17 (2H, m), of 4.05 (2H, arcs, J=6,8 Hz, 2.7 Hz), 4,16 (1H, m), 7,58 (1H, DD, J=8.1 Hz), 7,71 (1H, d, J=8.1 Hz), 8,08 (1H, d, J=8.1 Hz), 8,14 (1H, ).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 266 (M+H).

Compound 1C-3:

Ethyl ester of 2-(2-methyl-3-nitrobenzyl)-3-oxomalonate acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1C-2, except that 1-chloromethyl-2-methyl-3-nitrobenzene was used instead of 1-methyl bromide-2-fluoro-3-nitrobenzene.

1H NMR (Bruker 300 MHz, CDCl3) δ (ppm): a 7.62 (1H, d, J=8.0 Hz), 7,37 (1H, d, J=7,2 Hz), 7.23 percent (1H, m)to 4.16 (2H, q), of 3.73 (1H, t, J=7.4 Hz), or 3.28 (2H, m), 2,43 (3H, s), 2,24 (3H, s)to 1.21 (3H, t, J=7,1 Hz).

Compound 1C-46:

Ethyl ester of 2-(4-nitrobenzyl)-3-oxomalonate acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1C-2, except that 1-methyl bromide-4-nitrobenzene was used instead of 1-methyl bromide-2-fluoro-3-nitrobenz the La.

1H NMR (Bruker 300 MHz, CDCl3) δ (ppm): 8,14 (2H, d, J=8.7 Hz), was 7.36 (2H, d, J=8.7 Hz), 4,17 (2H, m), with 3.79 (1H, t, J=7,6 Hz)at 3.25 (2H, m), 2,24 (3H, s), 1,22 (3H, m).

Compound 1C-45:

Ethyl ester of 2-(2-nitrobenzyl)-3-oxomalonate acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1C-2, except that 1-methyl bromide-2-nitrobenzene was used instead of 1-methyl bromide-2-fluoro-3-nitrobenzene.

1H NMR (Bruker 300 MHz, CDCl3) δ (ppm): 8,00 (1H, d, J=8,4 Hz), 7,52-7,42 (3H, m), 4,22-4.09 to (2H, m)to 4.01 (1H, HF), 3,54-of 3.32 (2H, m), of 2.28 (3H, s)of 1.20 (3H, t, J=7,1 Hz).

Compound 1C-36:

Ethyl ester of 2-(4-fluoro-3-nitrobenzyl)-3-oxomalonate acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1C-2, except that 1-methyl bromide-3-nitro-4-torbenson used instead of 1-methyl bromide-2-fluoro-3-nitrobenzene.

1H NMR (270 MHz, DMSO-d6) δ (ppm): 8,07 (DD, 1H, J=7,1, 2.2 Hz), to 7.67 (m, 1H), 7,52 (DD, 1H, J=10,7, 8.6 Hz), 4,11 (m, 1H), 4,07 (q, 2H, J=7.0 Hz), 3,20 (m, 2H), of 2.21 (s, 3H), of 1.13 (t, 3H, J=7,0 Hz).

ESIMC m/z: 284 (M+H).

Compound 1C-51A:

Ethyl ester of 3-(methoxycarbonylamino)-2-(3-nitrophenylamino)butyric acid

3-Nitroaniline (2,92 g, 21,27 mmol) was added to p is the target ethyl 3-carbomethoxyamino (4,2 g, 21,13 mmol) (which is known in the literature) in THF (40 ml) and the mixture was stirred at 70°C during the day and night. After cooling to room temperature, to the mixture was added hexane, and the precipitated residue was filtered to obtain specified in the connection header (5,08 g, 71%).

1H NMR (270 MHz, DMSO-d6) δ (ppm): 10,10 (s, 1H), 7,55 (s, 1H), 7,46-7,31 (m, 2H), 7,11 (d, 1H, J=8.1 Hz), of 6.96 (d, 1H, J=7.4 Hz), 4,94 (d, 1H, J=7,7 Hz), 4,18 (q, 2H, J=7,1 Hz)to 3.67 (s, 3H)and 1.83 (s, 3H), of 1.21 (t, 3H, J=7,1 Hz).

ESIMC m/z: 339 (M+H).

Compound 1C-51:

Ethyl ester of 2-(3-nitrophenylamino)-3-oxomalonate acid

The solution trichloride titanium (10% solution in 20-30% HCl) was added to a solution of ethyl ester of 3-(methoxycarbonylamino)-2-(nitrophenylamino)butyric acid (compound 1C-51) (5.0 g, 14,78 mmol) in acetone (50 ml) and the mixture was stirred at room temperature for 1 h Then the reaction mixture was added water, extraction was performed with ethyl acetate and the organic extract was washed with water and saturated salt solution. After drying over magnesium sulfate, it was concentrated under reduced pressure to get crude product which was then purified column chromatography to obtain specified in the title compound (3.75 g, 95%) as a yellow oil.

1H NMR (270 MHz, DMSO-d6) δ (2:1 mixture of keto forms and anal) (ppm): 12,37 (s, 1/3H), 7,53 (t, 2/3H, J=22 Hz), 7,47-7,37 (m, 10/3H), 7,27 (t, 1/3H, J=2.2 Hz), 7,13 (m, 2/3H), 7,05 (d, 2/3H, J=8.6 Hz), 6,92 (d, 1/3H, J=9.1 Hz), to 5.35 (d, 2/3H, J=8.6 Hz), 4,25-4,11 (m, 6/3H), 2,31 (s, 6/3H), 1,99 (s, 3/3H), of 1.21 (t, 6/3H, J=7,1 Hz), a 1.08 (t, 3/3H, J=7,1 Hz).

ESIMC m/z: 267 (M+H).

Compound 1C-59:

Ethyl ester of 2-(2-nitrobenzylamine)-3-oxomalonate acid (known compound)

Rh2(SLA)4(30 mg, 0,063 mmol) was added to a solution of ethyldiazoacetate (1.0 g, 6,32 mmol) and 2-nitrobenzamide (1,05 g, 6,32 mmol) in methylene chloride (15 ml) and the mixture was stirred at 40°C during the day and night. Then to the reaction mixture was added water, extraction was performed with ethyl acetate and the organic extract was washed with water and saturated salt solution. After drying over magnesium sulfate, it was concentrated under reduced pressure to get crude product which was then purified column chromatography to obtain specified in the title compound (1.42 g, 77%) as a yellow oil.

1H NMR (270 MHz, DMSO-d6) δ (ppm): 9,58 (d, 1H, J=7.4 Hz), of 8.09 (d, 1H, J=7.9 Hz), to 7.84 (dt, 1H, J=7,5, 0.5 Hz), 7,73 (TD, 1H, J=7,8, 1.2 Hz), 7,63 (DD, 1H, J=7,4, 1.5 Hz), of 5.39 (d, 1H, J=7,6 Hz), is 4.21 (m, 2H), 2,30 (s, 3H), 1,24 (t, 3H, J=7,3 Hz).

ESIMC m/z: 295 (M+H).

Compound 1C-73:

Ethyl ester of 2-(5-nitrothiophen-2-ylmethyl)-3-oxomalonate acid

Ethylacetoacetate (0,64 ml of 5.06 mmol) was added to a mixture of sodium iodide (379 mg, 2,mol) using tetrahydrofuran. To the mixture was added 1 M solution of LiOtBu in THF (3,03 ml, 3.03 mmol) at 4°C and the mixture was stirred for 30 minutes and Then was added a solution of compound 1A-73 (600 mg, of 2.53 mmol) in tetrahydrofuran (2.0 ml) at 4°C and the mixture was heated to room temperature and was stirred for 22 hours was Added water (20 ml) and the organic layer was extracted with ethyl acetate. Then it was purified by chromatography on silica gel (hexane:ethyl acetate = 6:1) to obtain the specified title compound (623 mg, 91%).

1H-NMR (Bruker (ARX300), 300 MHz, CDCl3) δ (ppm): 7,79 (1H, d, J=4,20 Hz), 6,85 (1H, d, J=4,20 Hz), 4,27 (2H, q), a-3.84 (1H, t, J=6.87 in Hz)to 3.41 (2H, DD, J=6,87, of 7.25 Hz), was 2.34 (3H, s)of 1.32 (3H, t, J=6.87 in Hz).

Compound 1E-0-4:

3-(2-Fluoro-3-nitrobenzyl)-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

Chemical formula 13

Concentrated sulfuric acid (21,5 ml) was added at 0°C. to a mixture of resorcinol (14.8 g, 135 mmol) and ethyl ester of 2-(2-fluoro-3-nitrobenzyl)-3-oxomalonate acid (38,2 g, 135 mmol) and the reaction mixture was stirred at room temperature overnight. Then the reaction mixture was poured into water and the solid was filtered. It was washed with water and methanol to obtain specified in the connection header (28,3 g, 64%) as pale yellow powder.

1H NMR (270 MHz, DMSO-d6) δ (ppm): 7,98 (TD, J=8,9, and 1.6 Hz, 1H), 7,69 (d, J=8,9 Hz, 1H), 7,58 (TD, J=6,2, 4.3 Hz, 1H), to 7.32 (TD, J=8,9, 1.1 Hz, 1H), 6,83 (DD, J=8,9, and 2.4 Hz, 1H), 6,72 (d, J=2.4 Hz, 1H), was 4.02 (s, 2H), 2,43 (s, 3H).

ESIMC m/z: 330 (M+H).

Compound 1E-0-1:

3-(3-Nitrobenzyl)-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

Chemical formula 14

Specified in the title compound was synthesized using resorcinol and compound 1C-1 under the same conditions described in example obtain compound 1E-0-4.

1H NMR (270 MHz, DMSO-d6) δ (ppm): 2,44 (3H, s)4,08 (2H, s), 6,72 (1H, d, J=1.9 Hz), PC 6.82 (1H, DD, J=1,9, 8.6 Hz), 7,58 (1H, DD, J=7,8, and 7.8 Hz), 7,66-7,72 (2H, m), 8,05-8,08 (2H, m).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 312 (M+H).

Compound 1E-0-2:

3-(3-Nitrobenzyl)-7-hydroxy-4-methyl-6-fluoro-2-oxo-2H-1-benzopyran

Chemical formula 15

Specified in the title compound was synthesized using 4-forreporting and compound 1C-1 under the same conditions described in example obtain compound 1E-0-4.

1H NMR (270 MHz, DMSO-d6) δ (ppm): 2,43 (3H, s), of 4.13 (2H, s)of 6.71 (2H, d, J=7,6 Hz), 7,55-7,71 (3H, m), 8,05-8,07 (2H, m), 10,51 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 330 (M+H).

Compound 1E-0-3:

3-(3-Nitrobenzyl)-7-hydroxy-4-methyl-6-chloro-2-oxo-2H-1-benzopyran

Chemical formula 16

Specified in the header soy is inania synthesized using 4-chlororesorcinol and compound 1C-1 under the same conditions, described in the example of obtaining compounds 1E-0-4.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): 2,48 (3H, s), 4.09 to (2N, C)of 6.90 (1H, s), 7,55 (1H, t, J=7,7 Hz), of 7.70 (1H, d, J=7,7 Hz), 7,81 (1H, s), with 8.05 (1H, d, J=7,7 Hz), of 8.06 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 346 (M+H).

Compound 1E-0-5:

3-(2-Fluoro-3-nitrobenzyl)-7-hydroxy-4-methyl-6-fluoro-2-oxo-2H-1-benzopyran

Chemical formula 17

Specified in the title compound was synthesized using 4-forreporting and compound 1C-2 under the same conditions described in example obtain compound 1E-0-4.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.42 (3H, s), a 4.03 (2H, s), 6,92 (1H, d, J=7,6 Hz), 7,32 (1H, DD, J=7,7, 8.6 Hz), EUR 7.57 (1H, DD, J=7,7, 6.3 Hz), 7,69 (1H, d, J=12.0 Hz), to 7.99 (1H, DD, J=6,9, 8.6 Hz), 11,07 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 347 (M+H).

Compound 1E-0-6:

3-(2-Methyl-3-nitrobenzyl)-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized using resorcinol and compound 1C-3 under the same conditions described in example obtain compound 1E-0-4.

1H NMR (Bruker 300 MHz, DMSO-d6) δ (ppm): 10,51 (1H, s), of 7.69 (1H, d, J=8,8 Hz), the 7.65 (1H, d, J=8.0 Hz), 7,27 (1H, t, J=8.0 Hz), 7,12 (1H, d, J=7,6 Hz), at 6.84 (1H, DD, J=2,3, 8,8 Hz), 6,74 (1H, d, J=2.3 Hz), of 3.95 (2H, s), 2,42 (3H, s), of 2.33 (3H, s).

Compound 1E-0-7:

3-(3-Nitrobenzyl)-7-hydroxy-4-methyl-6-iodine-2-oxo-2H-1-benzopyran

Chemical formula 18

Specified in the title compound was synthesized using 4-yoketron and compound 1C-1 under the same conditions described in example obtain compound 1E-0-4.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): 2,44 (3H, s)4,07 (2H, s), PC 6.82 (1H, s), EUR 7.57 (1H, DD, J=5,4, 5,4 Hz), 7,69 (1H, d, J=2.7 Hz), 8,05-8,10 (3H, m), is 11.39 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 437 (M+H).

Compound 1E-0-8:

3-(3-Nitrobenzyl)-7-hydroxy-4-methyl-6-methyl-2-oxo-2H-1-benzopyran

Chemical formula 19

Specified in the title compound was synthesized using 4-methylresorcinol and compound 1C-1 under the same conditions described in example obtain compound 1E-0-4.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): 2,19 (3H, s), is 2.44 (3H, s)4,07 (2H, s), 6,74 (1H, s), 7,53-to 7.61 (2H, m), of 7.69 (1H, d, J=7.9 Hz), 8,02-of 8.09 (2H, m), 10,50 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 326 (M+H).

Compound 1E-0-36:

3-(4-Fluoro-3-nitrobenzyl)-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1E-0-4, and is shutting down, the compound 1C-36 was used instead of compound 1C-2.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): 7,98 (DD, 1H, J=7,1, 2.2 Hz), 7,69-to 7.61 (m, 2H), 7,49 (DD, 1H, J=10,7, 8.6 Hz), PC 6.82 (DD, 1H, J=8,9, and 2.4 Hz), 6,72 (d, 1H, J=2.4 Hz), 4,07 (s, 2H), of 2.38 (s, 3H).

ESIMC m/z: 371 (M+H).

Compound 1E-0-46:

3-(4-Nitrobenzyl)-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized using resorcinol and compounds 1C-46 in the same conditions described in example obtain compound 1E-0-4.

1H NMR (Bruker 300 MHz, DMSO-d6) δ (ppm): 10,48 (1H, s), 8,13 (2H, d, J=8,4 Hz), 7,66 (1H, d, J=8,8 Hz)to 7.50 (2H, d, J=8,4 Hz), PC 6.82 (1H, DD, J=2.3 Hz, 8,8 Hz), 6,72 (1H, d, J=2.3 Hz), 4,06 (2H, s)to 2.41 (3H, s).

Compound 1E-0-45:

3-(2-Nitrobenzyl)-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized using resorcinol and compounds 1C-45 in the same conditions described in example obtain compound 1E-0-4.

1H NMR (Bruker 300 MHz, DMSO-d6) δ (ppm): 10,55 (1H, s), of 7.97 (1H, d, J=8.0 Hz), 7,69 (1H, d, J=8,8 Hz), 7,56 (1H, d, J=7,6 Hz), 7,46 (1H, t, J=7,6 Hz), 7,20 (1H, d, J=7,6 Hz), 6,83 (1H, DD, J=2,3 8,8 Hz), 6,72 (1H, d, J=2.3 Hz), 4,17 (2H, s), is 2.37 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 311,76 (M+H).

Compound 1E-0-47:

4,7-Dihydroxy-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran

4,7-Digi the Roxy-2-oxo-2H-1-benzopyran (500 mg, of 2.81 mmol) and 3-nitrobenzaldehyde (424 mg, of 2.81 mmol) was added to a mixture of triethylamine (1.57 in ml, 11,23 mmol) and formic acid (1.07 ml, 28,07 mmol) and the resulting mixture was stirred at 100°C for 2 hours To the reaction mixture was added 5 N aqueous solution of hydrochloric acid and extraction was performed with ethyl acetate. The organic extract was washed with saturated salt solution and dried over magnesium sulfate and then concentrated under reduced pressure to obtain specified in the title compound (300 mg, 34%) as a pale yellow solid.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): 10,52 (s, 1H), 8,09-of 8.04 (m, 2H), 7,83 (d, 1H, J=8.7 Hz), 7,71 (d, 1H, J=7,6 Hz), EUR 7.57 (t, 1H, J=7,7 Hz), to 6.80 (DD, 1H, J=9,0, 2.4 Hz), 6,69 (d, 1H, J=2.0 Hz), of 3.95 (s, 2H).

ESIMC m/z: 314 (M+H).

Compound 1E-0-51:

7-Hydroxy-4-methyl-3-(3-nitrophenylamino)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1E-0-4, except that the ethyl ester of 2-(3-nitrophenylamino)-3-oxomalonate acid (compound 1C-51) was used instead of compound 1C-2.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): 10,50 (s, 1H), 8,13 (s, 1H), 7,65 (d, 1H, J=8.7 Hz), 7,51 (d, 1H, J=9.1 Hz), 7,42-7,34 (m, 2H), 7,01 (d, 1H, J=7,3 Hz)6,86 (DD, 1H, J=8,7, and 2.3 Hz), 6,77 (d, 1H, J=2.3 Hz), to 2.29 (s, 3H).

ESIMC m/z: 313 (M+H).

Compound 1E-0-59:

2-Nitro-N-(7-guide is hydroxy-4-methyl-2-oxo-2H-1-benzopyran-3-yl)benzamid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1E-0-4, except that the compound 1C-59 was used instead of compound 1C-2.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): is 10.68 (s, 1H), 10,26 (s, 1H), 8,12 (d, 1H, J=7,7 Hz), 7,89 (t, 1H, J=6.3 Hz), 7,80-7,74 (m, 3H), 7,71 (d, 1H, J=8.7 Hz), to 6.88 (DD, 1H, J=8,4, and 2.3 Hz), 6,77 (d, 1H, J=2.3 Hz), 2.40 a (s, 3H).

ESIMC m/z: 341 (M+H).

Compound 1E-0-72:

7-Hydroxy-4-methyl-3-(3-nitrobenzyl)-pyrano[2,3-b]pyridine-2-he

Zn(OTf)2(669 mg, of 1.84 mmol) was added to a suspension of pyridine-2,6-diol (204 mg, of 1.84 mmol) and ethyl ester of 2-(3-nitrobenzyl)-3-oxomalonate acid (488 mg, of 1.84 mmol) in methanol (10 ml) and the mixture was stirred at 75°C for 30 hours and Then the reaction mixture was poured into water and was extracted with ethyl acetate. The organic extract was washed with saturated salt solution and dried over magnesium sulfate. Then it was concentrated under reduced pressure to get crude product which was then purified column chromatography to obtain specified in the title compound (330 mg, 57%).

1H NMR (DMSO-d6, 270 MHz) δ (ppm): 2,44 (3H, s)4,07 (2H, s), to 6.67 (1H, d, J=8.6 Hz), EUR 7.57 (1H, DD, J=7,7, 7.9 Hz), 7,71 (1H, d, J=7,7 Hz), 8,05-to 8.14 (3H, m).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 313 (M+H).

Compound 1E-0-73:

3-(5-Nitrothiophen-2-ylmethyl)-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized using compound 1C-73 in the same conditions described in example obtain compound 1E-0-4.

1H-NMR (Bruker (ARX-300), 300 MHz, DMSO-d6) δ (ppm): of 10.58 (1H, s), 7,98 (1H, d, J=4,20), TO 7.68 (1H, d, J=8,77 Hz), 7,11 (1H, d, J=4,20 Hz), PC 6.82 (1H, DD, J=8,77 Hz), J=1,91 Hz), 6,72 (1H, d, J=2,29 Hz), 4,17 (2H, s), 2,47 (3H, s).

MS (Micromass, Quattromicro, ESI-) m/z: 315,83 (M-1).

Compound 1g-1-5:

2-Oxo-2H-3-(2-fluoro-3-nitrobenzyl)-4-methyl-6-fluoro-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 20

Sodium hydride (60%and 46.2 mg, of 1.16 mmol) was added to a solution of compound 1E-0-5 (364,9 mg, 1.05 mmol) in THF (4 ml) and the mixture was stirred at room temperature for 5 minutes To the mixture was added N,N-dimethylcarbamoyl (116 μl, of 1.26 mmol) and the mixture was stirred at room temperature for 1 h Then the reaction solution was added aqueous saturated solution of ammonium chloride (2 ml) and precipitated precipitated particles were collected by filtration. Then dropped into the sediment particles were washed with water to obtain specified in the connection header (407,8 mg, 93%) as a white solid.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.42 (3H, s)to 2.94 (3H, s)to 3.09 (3H, what), 4,07 (2H, s), 7,31-7,34 (1H, m), 7,49 (1H, d, J=6.8 Hz), to 7.59-7,63 (1H, m), 7,89 (1H, d, J=11,4 Hz), to 7.99 (1H, DD, J=6,9, 8,24 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 419 (M+H).

Compound 1g-1-1:

4-Methyl-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 21

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1g-1-5, except that the compound 1E-0-1 was used instead of compound 1E-0-5.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): to 8.12 (s, 1H), 8,07 (d, J=8,2 Hz, 1H), 7,86 (d, J=8.7 Hz, 1H), 7,72 (d, J=7.7 Hz, 1H), 7,58 (t, J=7.9 Hz, 1H), 7,26 (d, J=2.3 Hz, 1H), 7,19 (DD, J=8,7, 2.5 Hz, 1H), 4,14 (s, 2H), 3,07 (, 3H), of 2.93 (s, 3H), of 2.51 (s, 3H).

ESIMC m/z: 383 (M+H).

Compound 1g-1-2:

2-Oxo-2H-3-(3-nitrobenzyl)-4-methyl-6-fluoro-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 22

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1g-1-5, except that the compound 1E-0-2 was used instead of compound 1E-0-5.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): 2,50 (3H, s)to 2.94 (3H, s), is 3.08 (3H, s), 4,14 (2H, s), 7,49 (1H, d, J=6.8 Hz), 7,58 (1H, DD, J=7,9, 7.9 Hz), 7,72 (1H, d, J=7.9 Hz), 7,86 (1H, d, J=11,1 Hz), 8,08 (1H, m)to 8.12 (1H, s).

ESI (LC/MS mode registration of the emission of positively charged ions) m/z: 419 (M+H).

Compound 1g-1-3:

2-Oxo-2H-3-(3-nitrobenzyl)-4-methyl-6-chloro-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 23

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1g-1-5, except that the compound 1E-0-3 was used instead of compound 1E-0-5.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): to 8.12 (s, 1H), 8,08 (d, J=8,2 Hz, 1H), 8,02 (s, 1H), 7,72 (d, J=8,2 Hz, 1H), 7,58 (t, J=8,2 Hz, 1H), 7,50 (s, 1H), 4,14 (s, 2H), 3,11 (s, 3H), 2.95 and (s, 3H), of 2.51 (s, 3H).

ESI m/z: 417 (M+H).

Compound 1g-1-4:

2-Oxo-2H-3-(2-fluoro-3-nitrobenzyl)-4-methyl-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 24

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1g-1-5, except that the compound 1E-0-4 was used instead of compound 1E-0-5.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): at 2.93 (3H, s), of 3.07 (3H, s)4,08 (2H, s), 7,20 (1H, D. d, J=8,7, and 2.3 Hz), 7,26 (1H, d, J=2.3 Hz), 7,31 (1 H, t, d, J=8,3, 2.3 Hz), 7,60 (1H, DDD, J=8,3, 6,5, 1.8 Hz), 7,88 (1H, d, J=8.7 Hz), to 7.99 (1H, DDD, J=8,3, 6,5, 1.8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 401 (M+H).

Compound 1g-1-7:

2-Oxo-2H-3-(3-nitrobenzyl)-4-methyl-6-iodine-1-benzopyran-7-silt ether dimethylcarbinol the th acid

Chemical formula 25

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1g-1-5, except that the compound 1E-0-7 was used instead of compound 1E-0-5.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): 2,96 (3H, s), of 3.13 (3H, s), of 4.13 (2H, s), 7,38 (1H, s), EUR 7.57 (1H, DD, J=7,7, 8.1 Hz), 7,71 (1H, d, J=7,7 Hz), 8,08 (1H, d, J=8.1 Hz), 8,11 (1H, s), 8,24 (1H, s).

One of the peaks of CH3overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 509 (M+H).

Compound 1g-1-8:

2-Oxo-2H-3-(3-nitrobenzyl)-4-methyl-6-methyl-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 26

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1g-1-5, except that the compound 1E-0-8 used instead of compound 1E-0-5.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): of 2.23 (3H, s)to 2.94 (3H, s)to 3.09 (3H, s), of 4.13 (2H, s), 7,22 (1H, s), EUR 7.57 (1H, DD, J=7,4, 8.1 Hz), 7,71 (1H, d, J=7,4 Hz), 7,76 (1H, s), 8,08 (1H, d, J=8.1 Hz), 8,10 (1H, s).

One of the peaks of CH3overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 397 (M+H).

Compound 1g-1-9:

2-Oxo-2H-3-(3-nitrobenzyl)-4-methyl-6-cyano-1-benzopyran-7-silt ether Dima is ylcarbamate acid

Chemical formula 27

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1g-1-5, except that used the connection 1E-0-9 instead of compound 1E-0-5.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): 2,99 (3H, s), 3,14 (3H, s), of 4.12 (2H, s), 7,38 (1H, s), EUR 7.57 (1H, DD, J=7,7, 8.1 Hz), 7,71 (1H, d, J=7,7 Hz), 8,08 (1H, d, J=8.1 Hz), 8,11 (1H, s), 8,24 (1H, s).

One of the peaks of CH3overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 408 (M+H).

Compound 1g-1-38:

6-Carbarnoyl-4-methyl-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Acetic acid (5 ml) and concentrated sulfuric acid (5 ml) was added to the compound 1g-1-9 (1.2 g, 2,95 mmol) and the mixture was stirred at room temperature for 1.5 hours, the Reaction mixture was poured into sodium bicarbonate solution and was extracted with ethyl acetate. The organic extract was washed with saturated salt solution and dried over magnesium sulfate. Then it was concentrated under reduced pressure to get crude product which was then purified column chromatography to obtain specified in the title compound (1.1 g, 90%).

1H NMR (DMSO-d6, 270 MHz) δ (ppm): 2,90 (3H, s), 3,06 (3H, s), 4,15 2H, C), 7,29 (1H, s)to 7.50 (1H, users), 7,55-to 7.61 (2H, m), 7,70-7,73 (2H, m), 7,80 (1H, users), 8,01 (1H, s).

One of the methyl peaks overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 426 (M+H).

Compound 1g-1-39:

3-(3-Nitrobenzyl)-4-methyl-2-oxo-6-trimethylsilylethynyl-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Compound 1g-1-7 (1.45 g, 2,85 mmol), bis(triphenylphosphine)palladium (II) dichloride (100 mg, 0,143 mmol), copper iodide (I) (55 mg, 0.29 mmol), trimethylsilylacetamide (1.4 g of 14.3 mmol) and diisopropylethylamine (550 μl, 3.2 mmol) was mixed with 10 ml of anhydrous tetrahydrofuran and the mixture was heated and stirred at 45-55°C for 10 hours and Then it was purified by chromatography on silica gel (elution with methylene chloride) to obtain 1.06 g specified in the connection header.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): 0,21 (N, C)to 2.94 (3H, s), is 3.08 (3H, s), of 4.13 (2H, s), 7,39 (1H, s), EUR 7.57 (1H, t, J=8.0 Hz), of 7.70 (1H, d, J=8.0 Hz), 7,94 (1H, s), of 8.06 (1H, d, J=8.0 Hz), to 8.12 (1H, s).

One of the methyl peaks overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 449 (M+H).

Compound 1g-1-59:

3-(2-Nitrobenzylamine)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized in the same conditions is s, described in the example of obtaining compounds 1g-1-5, except that the compound 1E-0-59 was used instead of compound 1E-0-5.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): 10,44 (s, 1H), 8,13 (d, 1H, J=7,7 Hz), 7,92-7,88 (m, 2H), 7,80-7,76 (m, 2H), 7,33 (d, 1H, J=2.1 Hz), 7,25 (DD,1H, J=8,7, and 2.3 Hz), is 3.08 (s, 3H), of 2.92 (s, 3H), of 2.46 (s, 3H).

ESIMC m/z: 412 (M+H).

Compound 1g-1-72:

4-Methyl-3-(2-nitrobenzyl)-2-oxo-2H-pyrano[2,3-b]pyridine-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1g-1-5, except that the compound 1E-0-72 was used instead of compound 1E-0-5.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): 2,95 (3H, s), of 3.07 (3H, s), 4,14 (2H, s), 7,28 (1H, d, J=8,4 Hz), 7,58 (1H, DD, J=7,7, 8.1 Hz), 7,73 (1H, d, J=7,7 Hz), 8,05-to 8.14 (2H, m), 8,43 (1H, d, J=8,4 Hz).

The peak of CH3overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 384 (M+H).

Compound 1g-1b-1:

7 Isobutoxy-4-methyl-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-2-4, except that the compound 1E-0-1 was used instead of compound 1E-0-4 and Isopropylamine used instead of bromopyrimidine.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): 0,98 (3H, s), and 1.00 (3H, s), 1,95-2,11 (1H, m), 2,47 (3H, s), 3,86 (2H, d, J=6.5 Hz), 4,10 (2H, s), 6,93-7,06 (2H, m), 7,58 (1H, DD, J=8,1, 7,8 Hz), of 7.64-7,79 (2H, m), 8,00-8,11 (2H, m).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 368 (M+H).

2-Perately ether p-toluensulfonate acid

1 g (15.6 mmol) of 2-ftramadol was dissolved in pyridine (15 ml) and 6.5 g (34,1 mmol) p-toluensulfonate acid was added to the solution over 30 minutes under stirring on ice. The mixture was stirred at 0°C under nitrogen atmosphere for 3 h and after adding to the reaction mixture of 35 ml of ice water were extracted with 30 ml ethyl acetate. The obtained organic layer was washed three times with 30 ml of a 1 N solution of hydrochloric acid and then further washed with sodium carbonate solution and saturated salt solution. The obtained organic layer was dried over anhydrous sodium sulfate and the solvent drove under reduced pressure to obtain specified in the connection header (3,19 g, 94%) as a colourless oil.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.46 (3H, s), 4,14-of 4.25 (1H, m), 4,25 is 4.36 (1H, m), 4,43 is 4.36 (1H, m), br4.61-4,71 (1H, m), of 7.36 (2H, d, J=8.1 Hz), 7,81 (2H, d, J=8,1 Hz).

Compound 1g-1C-1:

7-(2-Floratone)-4-methyl-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran

Specified in the title compound which was intesively in the same conditions, described in the example of obtaining compounds 1g-2-4, except that the compound 1E-0-1 was used instead of compound 1E-0-4 and 2-perately ether p-toluensulfonate acid was used instead of bromopyrimidine.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): 2,43 (3H, s), 4,10 (2H, s), 4,29 is 4.36 (1H, m), 4,39-to 4.46 (1H, m), with 4.64-4,71 (1H, m), 4,82-4,89 (1H, m), of 6.96-7,07 (2H, m), 7,58 (1H, DD, J=8,1, 7,6 Hz), 7,71 (1H, d, J=8.1 Hz), 7,78 (1H, d, J=8.6 Hz), 8,01-8,11 (2H, m).

Compound 1g-1s-3:

6-Chloro-7-(2-floratone)-4-methyl-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-2-4, except that the compound 1E-0-3 was used instead of compound 1E-0-4 and 2-perately ether p-toluensulfonate acid was used instead of bromopyrimidine.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): 2,43 (3H, s), 4,11 (2H, s), 4,36-4,43 (1H, m), 4,46-of 4.54 (1H, m), 4,68-to 4.73 (1H, m), 4,86-4,91 (1H, m), 7,30 (1H, s), 7,58 (1H, DD, J=8,1, 7,8 Hz), 7,71 (1H, d, J=8.1 Hz), to 7.93 (1H, s), 8,04-8,11 (2H, m).

Compound 1g-1d-1:

4-Methyl-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether pyrrolidin-1-carboxylic acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1g-1-5, except that the compound 1E-0-1 is the objects of study were instead of compound 1E-0-5 and pyrrolidin-1-carbonylchloride used instead of the acid chloride of N,N-carbamino acid.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): 1,93-2,02, (4H, m), 2.49 USD (3H, s), 3,50 (2H, t, J=6.6 Hz)and 3.59 (2H, t, J=6.6 Hz), is 4.15 (2H, s), 7,14-7,19 (2H, m), 7,45 (1H, t, J=7.8 Hz), to 7.61-the 7.65 (2H, m), 8,06-8,10 (2H, m).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 409 (M+H).

Compound 1g-2-4:

4-Methyl-3-(2-fluoro-3-nitrobenzyl)-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 28

Compound 1E-0-4 (15 g, of 45.6 mmol) and 2-bromopyrimidine (72.4 g, 455 mmol) was dissolved in N,N-dimethylformamide (300 ml) and to the solution was added potassium carbonate (12,6 g and 91.2 mmol). The mixture was stirred at 80°C. in a nitrogen atmosphere for 1 h Then the reaction solution was added ethyl acetate and the solution washed with sodium bicarbonate solution, water and saturated salt solution. The organic layer was dried over anhydrous sodium sulfate and the solvent is kept at reduced pressure. The obtained residue was purified column chromatography on silica gel (hexane:ethyl acetate = 1:2) to obtain specified in the connection header (10,57 g, 57%) as pale yellow powder.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): 2,52 (3H, s), 4,10 (2H, s), 7,28 (1H, DD, J=8,8, 2.4 Hz), 7,30 and 7.36 (2H, m), 7,38 (1H, d, J=2.4 Hz), to 7.59-to 7.64 (1H, m), to 7.93 (1H, d, J=8,8 Hz), 7,97-8,03 (1H, m), 8,69 (2H, d, J=4.4 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 408 (M+H).

Compound 1g-2-1:

4-Methyl-3-(3-nitrobenzyl)-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 29

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-2-4, except that the compound 1E-0-1 was used instead of compound 1E-0-4.

1H NMR (CDCl3, 270 MHz) δ (ppm): 2,52 (3H, s), 4,17 (2H, s), 7,12 (1H, t, J=4,8 Hz), 7,20 (1H, DD, J=2,1, to 8.7 Hz), 7,20-7,40 (1H, m), 7,46 (1H, DD, J=7,7, 7,7 Hz), to 7.64 (1H, d, J=7,7 Hz), 7,72 (1H, d, J=8.7 Hz), 8.07-a 8,10 (2H, m), 8,59 (2H, d, J=4,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 390 (M+H).

Compound 1g-2-3:

4-Methyl-3-(3-nitrobenzyl)-7-(pyrimidine-2-yloxy)-6-chloro-2-oxo-2H-1-benzopyran

Chemical formula 30

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-2-4, except that the compound 1E-0-3 was used instead of compound 1E-0-4.

1H NMR (CDCl3, 270 MHz) δ (ppm): of 2.51 (3H, s)to 4.16 (2H, s), 7,13 (1H, t, J=4,8 Hz), 7,29 (1H, s), 7,45 (1H, t, J=7,7 Hz), a 7.62 (1H, d, J=7,7 Hz), of 7.75 (1H, s), of 8.06 (1H, d, J=7,7 Hz), 8,07 (1H, users), at 8.60 (2H, d, J=4,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 424 (M+H).

Compound 1g-2-47:

4-Hydroxy-3-(3-nitrobenzyl)-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-2-4, except that the compound 1E-0-47 was used instead of compound 1E-0-4.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): 8,69 (d, 2H, J=4,8 Hz)to 8.12 (m, 1H), 8,09-8,03 (DD, 2H), 7,73 (d, 1H, J=7,7 Hz), EUR 7.57 (t, 1H, J=7.9 Hz), 7,35-to 7.32 (m, 2H), 7,25 (DD, 1H, J=9,0, 2.2 Hz), 4.00 points (s, 2H).

ESIMC m/z: 392 (M+H).

Compound 1g-3-3:

4-Methyl-3-(3-nitrobenzyl)-7-(thiazol-2-yloxy)-6-chloro-2-oxo-2H-1-benzopyran

Chemical formula 31

Compound 1E-0-3 (2.0 g, 5,78 mmol) was dissolved in N,N-dimethylformamide (10 ml) and to the solution was added 2-bromothiazole (2,1 ml of 23.1 mmol), cesium carbonate (3.8 g, 11, 6 mmol) and copper iodide (I) (220 mg, of 1.16 mmol). The mixture was stirred at 110°C for 1 h under irradiation in a microwave oven (100 W). Then to the reaction solution were added ethyl acetate and the solution washed with water and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate and the solvent is kept at reduced pressure. The obtained residue was purified column chromatography on silica gel (mixture diclomelan:methanol = 20:1) to obtain the specified title compound (496 mg, 20%) as a pale yellow powder.

1H NMR (CDCl3, 270 MHz) δ (ppm): 2,50 (3H, s)to 4.15 (2H, s)6,94 (1H, d, J=3.8 Hz), 7.23 percent (1H, d, J=3.8 Hz), 7,44 is 7.50 (2H, m), 7,60-7,63 (1H m), of 7.75 (1H, s), 8.07-a 8,10 (2H, m).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 429 (M+H).

Compound 1g-3-1:

4-Methyl-3-(3-nitrobenzyl)-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 32

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-3-3, except that the compound 1E-0-1 was used instead of compound 1E-0-3.

1H NMR (CDCl3, 270 MHz) δ (ppm): 2,50 (3H, s)to 4.15 (2H, s), 6,93 (1H, d, J=3.8 Hz), 7,26-7,34 (3H, m), 7,43-7,50 (1H, m), to 7.61-7,66 (1H, m), 7,68 (1H, d, J=8,8 Hz), 8,05-8,10 (2H, m).

ESIMC (LC/MS in the registration mode, the positively charged ions) m/z: 395 (M+H).

Compound 1g-3-8:

4-Methyl-3-(3-nitrobenzyl)-7-(thiazol-2-yloxy)-6-methyl-2-oxo-2H-1-benzopyran

Chemical formula 33

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-3-3, except that the compound 1E-0-8 used instead of compound 1E-0-3.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): 2,28 (3H, s), 4,14 (2H, s), 7,29 (2H, s), 7,45 (1H, s), 7,58 (1H, DD, J=7,4, 8,2 Hz), 7,72 (1H, d, J=7,4 Hz), 7,87 (1H, s), 8,08 (1H, d, J=8,2 Hz), 8,11 (1H, s).

One of the peaks of CH3overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 409 (M+H).

Connect the tion 1g-11-3:

4-Methyl-3-(3-nitrobenzyl)-7-(thiophene-3-yl)-6-chloro-2-oxo-2H-1-benzopyran

2-Oxo-2H-3-(3-nitrobenzyl)-4-methyl-6-chloro-1-benzopyran-7-silt ether triptoreline acid (compound 1g-1E-3) was synthesized in the same conditions described in example obtain compound 1g-1-5, except that the compound 1E-0-3 was used instead of compound 1E-0-5 and anhydride triptoreline acid was used instead of dimethylcarbamodithioato.

Compound 1g-1E-3 (200 mg, 0,419 mmol) was added to a mixture of tetrahydrofuran (6 ml), thiophene-3-Bronevoy acid (160 mg, 1.25 mmol), tetrakis(triphenylphosphine)palladium (72 mg, 0,084 mmol) and K3RHO4(412 mg, 2.51 mmol) and the mixture was stirred at 80°C for 12 h and Then it was purified by chromatography on silica gel (hexane:ethyl acetate = 4:1) to obtain the specified title compound (121 mg).

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 8,10 (1H, s), 8,08 (1H, d, J=of 6.49 Hz), 7,73 (1H, s), the 7.65 (1H, d, J=8,01 Hz), to 7.59 (1H, DD, J=3,05, 1,53 Hz), 7,50-7,42 (3H, m), of 7.36 (1H, DD, J=5,34, 1,53 Hz), 4,17 (2H, s), of 2.51 (3H, s).

Compound 1g-12-1:

4-Methyl-3-(3-nitrobenzyl)-7-(pyridin-4-yl)-2-oxo-2H-1-benzopyran

2-Oxo-2H-3-(3-nitrobenzyl)-4-methyl-6-chloro-1-benzopyran-7-silt ether triptoreline acid (compound 1g-1E-1) was synthesized in the same conditions as described in the application is e obtain compound 1g-1-5, except that the compound 1E-0-1 was used instead of compound 1E-0-5 and anhydride triperoxonane acid was used instead of dimethylcarbamodithioato.

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-11-3, except that the compound 1g-1e-1 was used instead of compound 1g-1e-3 and pyridine-4-Bronevoy acid was used instead of thiophene-3-Bronevoy acid.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 8,73 (2H, d, J=of 6.49 Hz), 8,10 (1H, s), 8,08 (1H, d, J=9,16 Hz), 7,78 (1H, d, J=9,16 Hz), 7,71-7,44 (6N, m), 4,19 (2H, s), of 2.56 (3H, s).

Compound 1g-13-1:

4-Methyl-3-(3-nitrobenzyl)-7-(dibenzylamino)-2-oxo-2H-1-benzopyran

Mixed compound 1g-1e-1 (88 mg, 0.2 mmol), BINAP (11 mg, 0.02 mmol), palladium(II)acetate (3 mg, of 0.013 mmol), cesium carbonate (164 mg, 0.5 mmol) and benzophenone (154 mg, 0.24 mmol) and the mixture is boiled under reflux in nitrogen atmosphere for 3.5 hours and Then it was purified by chromatography on silica gel (mixture of ethyl acetate:hexane = 8:1 to 4:1) to obtain the specified title compound (49 mg, 52%).

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 8,08 (1H, d, J=1,91 Hz), of 8.06 (1H, d, J=9,54 Hz), 7,76 (2H, d, J=7,25 Hz), to 7.64 (1H, d, J=7,63 Hz), 7,55-7,41 (5H, m), 7,29 (3H, m), 7,13 (2H, d, J=4,96 Hz), 6,70 (1H, DD, J=8,39 Hz, J=2,29 Hz), 6,67 (1H, d, J=1,91 Hz), 4,10 (2H, s), 2,42 (3H, s).

Connect the s 1g-14-1:

4-Methyl-3-(3-nitrobenzyl)-7-amino-2-oxo-2H-1-benzopyran

2.5 ml of 2 N hydrochloric acid was added to a mixture of compound 1g-13-1 (6.2 g) in THF (50 ml) and the resulting mixture was stirred at room temperature for 20 minutes and Then was added 1 N aqueous sodium hydroxide solution and extraction was performed with methylene chloride. After removal of the solvent received the product (3.9 g, 96%) solidification using a mixture of hexane and ethyl acetate (2:1).

1H-NMR (Bruker (ARX-300), 300 MHz, DMSO-d6) δ (ppm): 8,05 (Ls, C)of 8.04 (1H, d, J=of 6.49 Hz), to 7.68 (1H, d, J=7,63 Hz), 7,56 (1H, t, J=7,63 Hz), 7,47 (1H, d, J=8,78 Hz), to 6.58 (1H, d, J=8,39 Hz), 6.42 per (1H, s), the 6.06 (2H, s), was 4.02 (2H, s), a 2.36 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 311,35 (M+1).

Compound 1g-15-1:

4-Methyl-3-(3-nitrobenzyl)-7-iodine-2-oxo-2H-1-benzopyran

To a mixture of compound 1g-14-1 (620 mg, 0,064 mmol), of 0.013 ml of concentrated sulfuric acid and 0.13 ml of water was added an aqueous solution (0,013 ml) NaNO2(4.6 mg, 0,068 mmol) at 0°C for 1 h and Then was added dropwise an aqueous solution (0,09 ml), potassium iodide (32 mg, 0,192 mmol) at 0°C for 30 min and the mixture was stirred at room temperature for 1 h and Then it was purified by chromatography on silica gel (hexane:ethyl acetate = 2:1) to obtain the specified title compound (25 mg, 92%).

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) is (ppm): 8,08 (1H, C)8,07 (1H, d, J=of 6.49 Hz), 7,72 (1H, d, J=,53 Hz), the 7.65 (2H, DD, J=8,39 Hz, J=1,91 Hz), 7,46 (1H, t, J=7,63 Hz), 7,35 (1H, d, J=8,39 Hz), 4,14 (2H, s), 2,48 (3H, s).

MS (Micromass, Quattromicro, ESI-) m/z: 420,43 (M-1).

5-Tributylstannyl

A solution of n-BuLi (4,14 ml, 10 mmol) in hexane was added dropwise to a solution of 5-bromothiazole in anhydrous tetrahydrofuran (and 0.46 ml, 5.0 mmol) at -78°C under nitrogen atmosphere for 30 min and the mixture was stirred for 1 h and Then was added dropwise a solution of Bu3SnCl (1,41 ml, 5.0 mmol) in THF for 30 min at

-78°C and after stirring for 2 h the mixture was heated to room temperature and stirred for 1 h was Added three drops of 1N HCl and the organic layer was extracted twice from aqueous layer with 10 ml of diethyl ether. The solvent drove with obtaining specified in the title compound (650 mg, 35 ml).

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): a 9.09 (1H, s), 7,88 (1H, s), 1,61-0,87 (N, m).

MS (Micromass, Quattromicro, ESI+) m/z: 376,07 (M+1).

Compound 1g-16-1:

4-Methyl-3-(3-nitrobenzyl)-7-(thiazol-5-yl)-2-oxo-2H-1-benzopyran

Mixed compound 1g-15-1 (150 mg, 0.36 mmol), 5-tributylstannyl (173 mg, 0.46 mmol), bis(triphenylphosphine)palladium dichloride (6.5 mg, 0,009 mmol), three(2-furyl)phosphine (4.3 mg, 0.02 mmol) and acetonitrile (4.5 ml) and the mixture is boiled under reflux in an argon atmosphere during the course the e night. Then the mixture was purified by chromatography on silica gel (hexane:ethyl acetate = 2:1; a mixture of methylene chloride:hexane:ethyl acetate = 1:1:1) to obtain the specified title compound (126 mg, 70%).

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 8,84 (1H, s), to 8.20 (1H, s), 8,10 (1H, s), of 8.09 (1H, d, J=8,39 Hz), 7,68 (2H, t, J=6.87 in Hz), 7,54 (2H, m), 7,47 (1H, t, J=7,63 Hz), 4,17 (2H, s), 2,53 Hz (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 397,04 (M+1).

2-Tributylstannyl

To a mixture of 2-bromothiazole (4.6 ml, 50 mmol) and anhydrous diethyl ether (50 ml) was added dropwise a solution of n-BuLi in hexane (22 ml, 55 mmol) at -78°C under nitrogen atmosphere and the mixture was stirred for 30 minutes and Then was added dropwise a solution of n-Bu3SnCl (14 ml, 50 mmol) in diethyl ether (20 ml) at -70°C and after stirring for 4 h the mixture was heated to room temperature and stirred for 1 h After adding water (50 ml) the organic layer was extracted three times with diethyl ether (50 ml) and the solvent drove away. Then it was purified by chromatography on silica gel (hexane:ethyl acetate = 20:1) to obtain the specified title compound (17 g, 90%).

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 8,17 (1H, d, J=3,05 Hz), 7,54 (1H, d, J=3,05 Hz), 1,65-1.55V (6N, m), 1,38-1,19 (N, m), 0,89 (N, t, J=7,25 Hz).

Compound 1g-17-1:

4-Methyl-3-(3-nitrobenzyl)-7-(thiazol-2-yl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-16-1, except that 2-tributylstannyl was used instead of compound 5-tributylstannyl.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 8:12 (1H, s), 8,08 (1H, d, J=8,01 Hz), 7,94 (3H, m), 7,72 (1H, d, J=8,01 Hz), to 7.67 (1H, d, J=7,63 Hz), of 7.48 (1H, d, J=8,01 Hz), 7,44 (1H, d, J=3,43 Hz), 4,18 (2H, s)to 2.54 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 397,04 (M+1).

Compound 1g-18-1:

4-Methyl-3-(3-nitrobenzyl)-7-(pyridin-3-yl)-2-oxo-2H-1-benzopyran

2-Oxo-2H-3-(3-nitrobenzyl)-4-methyl-1-benzopyran-7-silt ether triptoreline acid (compound 1g-1E-1) was synthesized in the same conditions described in example obtain compound 1g-1-5, except that the compound 1E-0-1 was used instead of compound 1E-0-5 and anhydride triptoreline acid was used instead of dimethylcarbamodithioato.

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-11-3, except that the compound 1g-1E-1 was used instead of compound 1g-1E-3 and pyridine-3-Bronevoy acid was used instead of thiophene-3-Bronevoy acid.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 8,91 (1H, d, J=1,91 Hz), 8,67 (1H, DD, J=4,58 Hz, J=1,53 Hz), 8,11 (1H, s), 8,08 (1H, DD, J=8,77 Hz, =1,91 Hz), a 7.92 (1H, dt, J=8,01 Hz, J=2,29 Hz), 7,78-7,42 (6N, m), 4,19 (2H, s), of 2.56 (3H, s).

Compound 1g-19-3:

4-Methyl-3-(3-nitrobenzyl)-6-chloro-7-(3-methoxyphenyl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-11-3, except that 3-phenoxypropanol acid was used instead of thiophene-3-Bronevoy acid.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): of 8.09 (1H, s), 8,08 (1H, d, J=of 6.49 Hz), 7,74 (1H, s), the 7.65 (1H, d, J=7,63 Hz), 7,49 (1H, t, J=8,01 Hz), 7,39 (1H, t, J=8,77 Hz), 7,35 (1H, s), 7,03 (1H, DD, J=7,63 Hz, J=1,14 Hz), 6,99-6,97 (2H, m), 4,18 (2H, s), 3,86 (3H, s), 2,52 (3H, s).

1-Methyl-2-tributylstannyl-1H-imidazol

n-BuLi (7,6 ml of 18.9 mmol) was added dropwise at -10°C. in a nitrogen atmosphere for 30 min to a solution of 1-methyl-1H-imidazole (1.6 ml, of 18.8 mmol) in anhydrous tetrahydrofuran (20 ml) and the mixture was stirred for 2.5 hours Then added to the solution Bu3SnCl (5,1 ml of 18.8 mmol) in tetrahydrofuran (12 ml) for 1 h at

-78°C and then the mixture was heated to room temperature and was stirred overnight. Specified in the header connection (5,48 g, 79%) was obtained by distillation in vacuum (140-142°C, 0.5 mm RT. Art.).

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 7,20 (1H, s), 7,01 (1H, s), 3,68 (3H, s), and 1.56 (6N, m), 1,37-1,15 (N, m)0,88 (N, t, J=7.2 Hz).

Compound 1g-20-1:

p> 4-Methyl-3-(3-nitrobenzyl)-7-(1-methyl-1H-imidazol-2-yl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-16-1, except that 1-methyl-2-tributylstannyl-1H-imidazole was used instead of 5-tributylstannyl.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 8,10 (1H, s), 8,08 (1H, d, J=8,01 Hz), 7,74 (2H, s), to 7.67 (1H, d, J=7,25 Hz), 7,58 (1H, s), 7,47 (1H, t, J=7,63 Hz), 7,18 (1H, d, J=l,14 Hz),? 7.04 baby mortality (1H, d, J=0,76 Hz), 4,19 (2H, s), 3,85 (3H, C)to 2.55 (3H, s).

Compound 1g-21-3:

4-Methyl-3-(3-nitrobenzyl)-6-chloro-7-(5-acetylthiophene-2-yl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-11-3, except that 5-acetylthiophene-2-Bronevoy acid was used instead of thiophene-3-Bronevoy acid.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 8,15 with 8.05 (3H, m), 8,02 (1H, d, J=4,19 Hz), 7,83 (1H, s), 7,72 (2H, DD), 7,60 (1H, t), of 4.16 (2H, s), 2,60 (3H, s)to 2.54 (3H, s).

Compound 1g-22-1:

4-Methyl-3-(3-nitrobenzyl)-7-(3-acetylphenyl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-11-3, except that the connection de-1 was used instead of compound 1g-1E-3 and 3-acetylphenylalanine acid was used instead of thiophene-3-Bronevoy acid.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 8,23 (1H, t), with 8.05 (2H, m), 7,88 (1H, d, J=7,63 Hz), 7,82 (1H, d, J=7,63 Hz), of 7.75 (1H, m=1,49 Hz), 7,73 (1H, d, J=8,01 Hz), to 7.61 (3H, m), 7,45 (1H, t), 4,22 (2H, s)to 2.65 (3H, s)to 2.46 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 414,08 (M+1).

Compound 1g-23-1:

4-Methyl-3-(3-nitrobenzyl)-7-(4-acetylphenyl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-11-3, except that the compound 1g-1E-1 was used instead of compound 1g-1E-3 and 4-acetylphenylalanine acid was used instead of thiophene-3-Bronevoy acid.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 8,01 (4H, m), a 7.85 (1H, d, J=8,77 Hz), to 7.64 (4H, m), 7,45 (1H, t), 6,85 (1H, d, J=8,39 Hz), 4,22 (2H, s)to 2.65 (3H, s)to 2.46 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 414,08 (M+1).

Compound 1g-28-1:

4-Methyl-3-(3-nitrobenzyl)-7-(4-N,N-dimethylaminophenyl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-11-3, except that the compound 1g-1E-1 was used instead of compound 1g-1E-3 and 4-N,N-dimethylaminopropionic acid was used instead of thiophene-3-Bronevoy acid.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 8,11 (2H, etc, J=8,77 Hz), 7,53 (7H, m), is 6.78 (2H, d, J=8,77 Hz) 4,22 (2H, C)3,10 (6N, (C), 2,52 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 415,25 (M+1).

1-Methyl-5-tributylstannyl-1H-imidazol

To a solution of 1-methylimidazole (1.6 ml, of 18.8 mmol) in anhydrous tetrahydrofuran (10 ml) was added dropwise a mixture of n-BuLi (18 ml, 45 mmol) and TMEDA (6,7 ml, 44 6 mmol) at -20°C in nitrogen atmosphere. After stirring for 30 min the mixture was heated to room temperature and stirred for another 1 h After cooling to -20°C. to the mixture was added dropwise a solution of n-Bu3SnCl (12.5 ml, of 46.4 mmol) in tetrahydrofuran (10 ml) and was stirred for 17 hours the Reaction was stopped by adding water (15 ml) and then twice carried out the extraction with ethyl acetate (20 ml). Then the mixture was purified by chromatography on silica gel (mixture of ethyl acetate:methanol = 96:4) to obtain the specified title compound (2.2 g, 32%).

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): to 7.61 (1H, s), 7,02 (1H, s)to 3.67 (3H, s), 1,48-1,56 (6N, m)of 1.29 to 1.37 (6N, m)1,09 (6N, t, J=8,4 Hz), 0,89 (N, t, J=7.2 Hz).

MS (Micromass, Quattromicro, ESI+) m/z: 372,99 (M+2).

Compound 1g-32-1:

4-Methyl-3-(3-nitrobenzyl)-7-(3-methyl-3H-imidazol-4-yl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-16-1, except that 1-methyl-5-tributylstannyl-1H-imidazole was used instead of tributylstannyl.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 8,08 (2H, d, J=6.9 Hz), of 7.70 (2H, m), 7,58 (1H, s), 7,47 (1H, t, J=7.8 Hz), 7,38 (2H, m), 7,26 (1H, d, J=3,9 Hz), 4,18 (2H, s), 3,76 (3H, s), of 2.53 (3H, s).

Compound 1h-1-5:

2-Oxo-2H-3-(2-fluoro-3-aminobenzyl)-4-methyl-6-fluoro-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 34

The tin chloride (II) dihydrate (923 mg, 4.09 to mmol) was added to a solution of compound 1g-1-5 (342,5 mg, 0,819 mmol) in a mixture of ethanol/ethyl acetate (volume ratio 1:1, 50 ml) and the mixture was stirred at 80°C for 3 hours To the reaction solution were added ethyl acetate and the organic layer was washed with sodium carbonate solution and saturated salt solution and dried over anhydrous magnesium sulfate. The solvent drove under reduced pressure to obtain specified in the connection header (311,3 mg, 98%) as a white solid.

1H NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.41 (3H, s), 2,95 (3H, s)to 3.09 (3H, s)4,08 (2H, s), 6,21-of 6.26 (1H, m), 6,58 to 6.75 (2H, m), 7,47 (1H, d, J=6.8 Hz), 7,83 (1H, d, J=11.2 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 389 (M+H).

Compound 1h-1-1:

2-Oxo-2H-3-(3-aminobenzyl)-4-methyl-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 35

Specified in the title compound was synthesized in the same conditions, is the quiet is described in the example of obtaining compounds 1h-1-5, except that the compound 1g-1-1 was used instead of compound 1g-1-5.

1H NMR (CDCl3, 270 MHz) δ (ppm): to 2.42 (3H, s), 3,03 (3H, s), of 3.13 (3H, s), of 3.60 (2H, users), of 3.97 (2H, s), 6,51 (1H, DD, J=2.0 a, 7,7 Hz), to 6.58 (1H, s), only 6.64 (1H, d, J=7,7 Hz), 7,02 for 7.12 (3H, m), to 7.59 (1H, d, J=8,9 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 352 (M+H).

Compound 1h-1-2:

2-Oxo-2H-3-(3-aminobenzyl)-4-methyl-6-fluoro-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 36

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-1-2 was used instead of compound 1g-1-5.

1H NMR (CD3OD, 270 MHz) δ (ppm): 2,44 (3H, s), to 3.02 (3H, s)and 3.15 (3H, s), of 3.95 (2H, s), 6,54-6,60 (2H, m), 7,00 (1H, DD, J=7,6, 7,6 Hz), 7,29 (1H, d, J=6.6 Hz), to 7.64 (1H, d, J=11,1 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 371 (M+H).

Compound 1h-1-3:

2-Oxo-2H-3-(3-aminobenzyl)-4-methyl-6-chloro-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 37

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-1-3 was used instead of compound 1g-1-5.

1H-NMR (CDCl 3, 270 MHz) δ (ppm): 2,40 (3H, s), 3.04 from (3H, s)and 3.15 (3H, s), of 3.96 (2H, s), 6,45-of 6.65 (3H, m), 7,05 (Ls, DD, J=7,7 Hz), 7,25 (1H, s), to 7.64 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 387 (M+H).

Compound 1h-1-4:

2-Oxo-2H-3-(2-fluoro-3-aminobenzyl)-4-methyl-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 38

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-1-4 was used instead of compound 1g-1-5.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): at 2.93 (3H, s), 3,06 (3H, s), 3,91 (2H, s), 5,07 (2H, users), to 6.22 (1H, ushort, J=7,3 Hz), 6,55 to 6.75 (2H, m), 7,17 (1H, DD, J=8,7, and 2.3 Hz), 7,24 (1H, d, J=2.3 Hz), 7,83 (1H, d, J=8.7 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 371 (M+1H).

Compound 1h-1-7:

2-Oxo-2H-3-(3-aminobenzyl)-4-methyl-6-iodine-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 39

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-1-7 was used instead of compound 1g-1-5.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 2,43 (3H, s), 2,96 (3H, s), of 3.13 (3H, s), 3,83 (2H, s), 4,96 (2H, users), 6,35-6,38 (3H, m), 6.89 in (1H, DD, J=7,8, and 7.8 Hz), 7,37(1H, C), by 8.22 0,N, C).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 479 (M+H).

Compound 1h-1-8:

2-Oxo-2H-3-(3-aminobenzyl)-4-methyl-6-methyl-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 40

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-1-8 was used instead of compound 1g-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,22 (3H, s), 2,43 (3H, s)to 2.94 (3H, s), 3,10 (3H, s), 3,83 (2H, s), 4,96 (2H, users), 6,35-6,38 (3H, m), 6.90 to (1H, DD, J=8,1, 8.1 Hz), 7,21 (1H, s), 7,73 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 367 (M+H).

Compound 1h-1-9:

2-Oxo-2H-3-(3-aminobenzyl)-4-methyl-6-cyano-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 41

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-1-9 was used instead of compound 1g-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.46 (3H, s), of 2.97 (3H, s), of 3.12 (3H, s), a-3.84 (2H, s), 4,96 (2H, users), 6,36-6,38 (3H, m), 6.90 to (1H, DD, J=7,9, 7.9 Hz), to 7.59 (1H, s), 8,44 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 378 (M+H).

Connected the e 1h-1-10:

2-Oxo-2H-3-(2-aminopyridine-4-ylmethyl)-4-methyl-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 42

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1g-1-5, except that compound 5d-0-10 was used instead of compound 1E-0-5.

1H-NMR (300 MHz) (DMSO-d6) δ (ppm): to 2.42 (3H, s), 2,93, (3H, s), 3,06 (3H, s), 3,82 (2H, s), of 5.75 (2H, users), to 6.19 (1H, s), 6,37 (1H, DD, J=1,52, of 5.34 Hz), 7,18 (1H, DD, J=2,28, 8,77 Hz), 7,25 (1H, d, J=2,28 Hz), 7,76 (1H, d, J=5,34 Hz), to 7.84 (1H, d, J=8,77 Hz).

Compound 1h-1-11:

2-Oxo-2H-3-(2-aminopyridine-4-ylmethyl)-4-methyl-6-fluoro-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 43

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1g-1-5, except that compound 5d-0-11 used instead of compound 1E-0-5.

1H-NMR (300 MHz) (DMSO-d6) δ (ppm): to 2.41 (3H, s)to 2.94 (3H, s), is 3.08 (3H, s), 3,82 (2H, s), of 5.75 (2H, users), to 6.19 (1H, s), 6,37 (1H, d, J=4,95 Hz), of 7.48 (1H, d, J=7,24 Hz), 7,76 (1H, d, J=5,72 Hz), the 7.85 (1H, d, J=at 9.53 Hz).

Compound 1h-1-13:

3-(6-Aminopyridine-2-ylmethyl)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 44

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1g-1-5, except that compound 5d-0-13 used instead of compound 1E-0-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.42 (3H, s), with 2.93 (3H, s), of 3.07 (2H, d), 3,88 (2H, s), 5,79 (2H, users), 6,23 (1H, d, J=8.1 Hz), 6,30 (1H, d, J=8.1 Hz), 7,15-7,26 (3H, m), 7,83 (1H, d, J=10,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 354 (M+H).

Compound 1h-1-14:

3-(6-Aminopyridine-2-ylmethyl)-6-fluoro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 45

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1g-1-5, except that compound 5d-0-14 was used instead of compound 1E-0-5.

1H-NMR (CDCl3, 270 MHz) δ (ppm): 2,45 (3H, s), 3.04 from (3H, s)to 3.09 (3H, s), Android 4.04 (2H, s), of 6.31 (1H, d, J=7.8 Hz), is 6.54 (1H, d, J=7.8 Hz), 7,15-7,40 (3H, m).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 372 (M+H).

Compound 1h-1-15:

3-(6-Aminopyridine-2-ylmethyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 46

Specified in the title compound was synthesized under the same conditions described in example floor the treatment of compound 1g-1-5, except that compound 5d-0-15 was used instead of compound 1E-0-5.

1H-NMR (CDCl3, 270 MHz) δ (ppm): to 2.46 (3H, s), 3,05 (3H, s), 3,17 (3H, s), Android 4.04 (2H, s), of 6.31 (1H, d, J=7.8 Hz), 6,55 (1H, d, J=7.8 Hz), 7,20-to 7.35 (2H, m), 7,66 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 388 (M+H).

Compound 1h-1-4F:

3-(3-Amino-2-terbisil)-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 47

Ethyl acetate (2.0 ml) was added to 4-vermeil-3-(2-fluoro-3-nitrobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid (20.5 mg) (compound 6C-1-4) and the resulting suspension was added tin chloride (II) dihydrate (60 mg) while stirring at room temperature. The suspension is boiled under reflux for 1.5 h and after cooling to room temperature was added a saturated solution of sodium bicarbonate and the mixture was extracted with ethyl acetate. The resulting organic extract was washed with saturated salt solution and the organic layer was dried over anhydrous magnesium sulfate. The solvent is then drove away under reduced pressure to obtain specified in the title compound (19.5 mg).

1H-NMR (CDCl3, 270 MHz) δ (ppm):3,03 (3H, s), of 3.13 (3H, s), 4.09 to (2N, C), to 5.66 (2H, d, J=46,8 Hz), 6,62 (1H, ushort, 7.9 Hz), of 6.65 (1H, TD, J=7,9, and 1.0 Hz), 83 (1H, DD, J=7,9, 1.0 Hz), 7,12 (1H, DD, J=8,2, 2.3 Hz), to 7.15 (1H, d, J=2.3 Hz), 7,76 (1H, DD, J=8,2, 2,3 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 389 (M+H).

Compound 1h-1-1F:

3-(3-Aminobenzyl)-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 48

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-4F, except that the compound 6c-1-1 was used instead of compound 6c-1-4.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): at 2.93 (3H, s), of 3.07 (3H, s), 3,91 (2H, s), to 4.98 (2H, users), of 5.81 (2H, d, J=46,3 Hz), 6,29-to 6.43 (3H, m)6,91 (1H, t, J=8,2 Hz), 7,21 (1H, DD, J=8,7, and 2.3 Hz), 7,30 (1H, d, J=2.3 Hz), 7,89 (1H, d, J=8,7, 2,3 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 371 (M+H).

Compound 1h-1-2F:

3-(3-Aminobenzyl)-6-fluoro-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 49

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-4F, except that the compound 6c-1-2 was used instead of compound 6c-1-4.

1H-NMR (CDCl3, 270 MHz) δ (ppm): 3.04 from (3H, s)and 3.15 (3H, s), a 4.03 (2H, users), 5,59 (2H, d, J=47,0 Hz), 6,50-6,60 (3H, m), 7,01-7,10 (1H, m), 7,20-7,30 (1H, m), 7,54 (2H, 1H, DD, J=10,5, ,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 389 (M+H).

Compound 1h-1-3F:

6-Chloro-4-vermeil-3-(3-aminobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 50

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-4F, except that the compound 6c-1-3 was used instead of compound 6c-1-4.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): of 8.04 (s, 1H), 7,54 (s, 1H), 6.90 to (t, J=7.8 Hz, 1H), 6,36 (m, 3H), of 5.84 (d, J=46,0 Hz, 2H), 3,92 (s, 2 H), 3,11 (s, 3H), 2.95 and (s, 3H).

ESIMC m/z: 405 (M+H).

Compound 1h-1-38:

3-(3-Aminobenzyl)-6-carbarnoyl-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-1-38 used instead of compound 1g-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,47 (3H, s), 2,90 (3H, s), 3,05 (3H, s), 3,85 (2H, s), equal to 4.97 (2H, s), 6,35-6,38 (3H, m), 6.90 to (1H, t, J=7.8 Hz), 7,28 (1H, s)to 7.50 (1H, s), 7,80 (1H, s), 7,98 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 396 (M+H).

Compound 1h-1-39:

3-(3-Aminobenzyl)-4-methyl-2-oxo-6-trimethylsilylethynyl-2H-1-benzopyran-7-silt ether is metilcarbonievy acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-1-39 used instead of compound 1g-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 0,23 (N, C)of 2.44 (3H, s)to 2.94 (3H, s), 3,11 (3H, s), 3,82 (2H, s), 4,96 (2H, s), 6,12-x 6.15 (3H, m), of 6.66 (1H, t, J=8.1 Hz), 7,14 (1H, s), to 7.68 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 449 (M+H).

Compound 1h-1-40:

3-(3-Aminobenzyl)-6-ethinyl-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

TBAF (1.0 M solution in 0,245 ml THF) was added to a solution of compound 1g-1-39 (100 mg, 0,223 mmol) in THF (2 ml) and the mixture was stirred at room temperature for 1 h Then the reaction mixture was concentrated under reduced pressure to get crude product which was then purified column chromatography to obtain specified in the title compound (77 mg, 92%).

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,44 (3H, s)to 2.94 (3H, s)to 3.09 (3H, s), 3,83 (2H, s), of 4.45 (1H, s), equal to 4.97 (1H, users), 6,35-6,38 (3H, m), of 6.96 (1H, t, J=8.0 Hz), 7,38 (1H, s), of 7.97 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 377 (M+H).

Compound 1h-1-59:

3-(2-Aminobenzoylamino)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol to the slots

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-1-59 used instead of compound 1g-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 9,63 (s, 1H), 7,86 (d, 1H, J=8.7 Hz), 7,76 (d, 1H, J=6.6 Hz), 7,31 (d, 1H, J=2.3 Hz), 7,25-7,20 (m, 2H), 6.75 in (d, 1H, J=8,2 Hz), to 6.58 (t, 1H, J=7,3 Hz), 6,50 (s, 2H), is 3.08 (s, 3H), 2,94 (s, 3H), of 2.36 (s, 3H).

ESIMC m/z: 382 (M+H).

Compound 1h-1d-1:

3-(3-Aminobenzyl)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether pyrrolidin-1-carboxylic acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-1d-1 was used instead of compound 1g-1-5.

1H-NMR (CDCl3, 270 MHz) δ (ppm): 1,90-2,04 (4H, m), 2,42 (3H, s), 3,50 (2H, t, J=6.6 Hz), 3,56-3,61 (4H, m), of 3.97 (2H, s), of 6.49 of 6.66 (3H, m), 7,05 (1H, t, J=7.8 Hz), 7,09-7,17 (2H, m), to 7.59 (1H, d, J=7,4 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 379 (M+H).

Compound 1h-2-1:

4-Methyl-3-(3-aminobenzyl)-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 51

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that the soybean is inania 1g-2-1 was used instead of compound 1g-1-5.

1H-NMR (CDCl3, 270 MHz) δ (ppm): 2,45 (3H, s), 3,60 (1H, users), to 3.99 (2H, s), of 6.52 (1H, DD, J=2.0 a, 7,6 Hz), to 6.57 (1H, s), only 6.64 (1H, d, J=7,6 Hz), 7,06 (1H, DD, J=7,6, 7,6 Hz), 7,11 (1H, t, J=4,8 Hz), 7,16 (1H, DD, J=2,3, 8,7 Hz), 7.23 percent (1H, d, J=2.3 Hz), to 7.68 (1H, d, J=8.7 Hz), 8,59 (2H, d, J=4,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 360 (M+H).

Compound 1h-2-3:

4-Methyl-3-(3-aminobenzyl)-7-(pyrimidine-2-yloxy)-6-chloro-2-oxo-2H-1-benzopyran

Chemical formula 52

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-2-3 was used instead of compound 1g-1-5.

1H-NMR (CDCl3, 270 MHz) δ (ppm): to 2.42 (3H, s), of 4.00 (2H, s), of 6.52 (1H, d, J=7,7 Hz), 6,55 (1H, users), 6,63 (1H, d, J=7,7 Hz),? 7.04 baby mortality (1H, t, J=7,7 Hz), 7,10 (1H, t, J=4,8 Hz), 7,26 (1H, s), 7,72 (1H, s), at 8.60 (2H, d, J=4,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 394 (M+H).

Compound 1h-2-4:

4-Methyl-3-(2-fluoro-3-aminobenzyl)-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 53

The scheme of synthesis 1

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-2-4 was used instead of compound 1g-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ(ppm): 2,45 (MN, C)3,93 (2H, s)5,08 (2H, users), and 6.25 (1H, DDD, J=7,2, 1.7 Hz, JHF=7,2 Hz), is 6.61 (1H, DDD, J=8,2) and 1.7 Hz, JHF=8,2 HZ), WAS 6.73 (1H, DD, J=8,2, 7,2 Hz), 7,26 (1H, DD, J=8,8, 2.4 Hz), 7,34 (1H, t, J=4,8 Hz), 7,37 (1H, d, J=2.4 Hz), 7,89 (1H, d, J=8,8 Hz), 8,68 (2H, d, J=4,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 378 (M+H).

Compound 1h-2-4S2:

3-{2-Fluoro-3-aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzothiophen

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that compound 5d-0-4S2 was used instead of compound 4A-0-4.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): was 4.02 (2H, s), 5,09 (2H, s), 6,11 (1H, DD, J=7,0 Hz, JHF=7,0 Hz), 6,60 (1H, DD, J=8.5 Hz, JHF=8,5 Hz), of 6.71 (1H, DD, J=7,7, 7,7 Hz), 7,28 (1H, D. d, J=8,9, and 2.3 Hz), 7,31-7,42 (2H, m), to 7.61-to 7.64 (1H, m), 8,67-8,71 (2H, m).

The peak of CH3overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 394 (M+H).

Compound 1h-2-5:

2-Oxo-2H-3-(2-fluoro-3-aminobenzyl)-4-methyl-6-fluoro-7-(pyrimidine-2-yloxy)-1-benzopyran

Chemical formula 54

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-2-4, except that the compound 4A-0-5 was used instead of the joint is 1E-0-4.

1H-NMR (CD3OD, 270 MHz) δ (ppm): 2,39 (3H, s), a 4.03 (2H, s), 6,29-to 6.43 (1H, m), 6,69-of 6.78 (2H, m), 7,28-7,39 (3H, m), 7.68 per-7,72 (1H, m), 7,98 (1H, m).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 396 (M+H).

Compound 1h-2-6:

4-Methyl-3-(2-methyl-3-aminobenzyl)-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that compound 4A-0-6 was used instead of compound 4A-0-4.

1H NMR (Bruker 300 MHz, CDCl3) δ (ppm): 8,61 (2H, d, J=5.0 Hz), of 7.70 (1H, d, J=8,8 Hz), 7,26 (1H, d, J=3.1 Hz), 7,18 (1H, DD, J=2.7, and an 8.8 Hz), 7,12 (1H, t, J=4,8 Hz), to 6.88 (1H, t, J=7.8 Hz), 6,59 (1H, d, J=7,6 Hz), 6,32 (1H, d, J=a 7.6 Hz), was 4.02 (2H, s), of 3.73-3,63 (2H, usher.), of 2.35 (3H, s), 2,22 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 373,97 (M+H).

Compound 1h-2-10:

4-Methyl-3-(2-aminopyridine-4-ylmethyl)-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 55

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-2-4, except that compound 5d-0-10 was used instead of compound 1E-0-4.

1H NMR (CD3OD, 270 MHz) δ (ppm): at 2.36 (3H, s), 3,85 (2H, s), 6,32 (1H, users), 6.42 per (1H, d, J=5.7 Hz), 7,10-7,20 (3H, m), 7,66 (1H, d, J=4.9 Hz), of 7.75 (1H, d, J=8.6 Hz), charged 8.52 (2H, d, J=4,9 Hz).

<> ESI (LC/MS in the registration mode, the positively charged ions) m/z: 361 (M+H).

Compound 1h-2-12:

4-Methyl-3-(2-aminopyridine-4-ylmethyl)-7-(pyrimidine-2-yloxy)-6-chloro-2-oxo-2H-1-benzopyran

Chemical formula 56

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-2-4, except that compound 5d-0-12 used instead of compound 1E-0-4.

1H-NMR (CDCl3, 270 MHz) δ (ppm): to 2.42 (3H, s), of 3.96 (2H, s), 6.35mm (1H, users), 6,53 (1H, d, J=6.5 Hz), 7,13 (1H, DD, J=4.9 Hz), 7,31 (1H, s), 7,74 (1H, s), of 7.96 (1H, d, J=6.5 Hz), 8,59 (2H, d, J=4,9 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 395 (M+H).

Compound 1h-2-4F:

3-(3-Amino-2-terbisil)-4-vermeil-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 57

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 6c-2-4 was used instead of compound 1g-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 8,68 (d, J=4.9 Hz, 2H), 7,94 (DD, J=8,9, and 2.4 Hz, 1H), 7,41 (d, J=2.2 Hz, 1H), 7,33 (t, J=4.6 Hz, 1H), 7,29 (DD, J=8,7, 2.2 Hz, 1H), 6,72 (t, J=7,6 Hz, 1H), 6,60 (TD, J=8,1, 1,6 Hz, 1H), 6,24 (t, J=6.2 Hz, 1H), of 5.83 (d, J=46.2 Hz, 2H), to 5.08 (s, 2H), 4.00 points (s, 2H).

ESIMC m/z: 396 (M+H).

Compound 1h-2-16:

3-(3-Fluoro-2-amine is pyridine-4-ylmethyl)-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that compound 5d-0-16 was used instead of compound 4A-0-4.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,45-to 2.55 (3H, m), of 3.94 (2H, s), 6,12 (2H, users), 6,28 (1H, DD, J=4,7 Hz), 7,27 (1H, DD, J=8.6 Hz, J=2.1 Hz), 7,34 (1H, DD, J=4.9 Hz), 7,38 (1H, d, J=2.1 Hz), 7,58 (1H, d, J=4,7 Hz), to $ 7.91 (1H, d, J=8.6 Hz), 8,68 (2H, d, J=4,7 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 479 (M+H).

Compound 1h-2-17:

3-(2-Amino-3-herperidin-4-ylmethyl)-6-fluoro-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that compound 5d-0-17 was used instead of compound 4A-0-4.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,45 (3H, s), of 3.94 (2H, s), 6,13 (2H, s), 6,28 (1H, t, J=5,1 Hz), 7,38 (1H, t, J=4,8 Hz), to 7.59 (1H, d, J=5,1 Hz), the 7.65 (1H, d, J=6.8 Hz), 7,92 (1H, d, J=11.5 Hz), to $ 7.91 (1H, d, J=11.5 Hz), to 8.70 (2H, d, J=4,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 397 (M+H).

Compound 1h-2-19:

3-(3-fluoro-2-aminopyridine-4-ylmethyl)-4-methyl-6-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

The decree of the TES in the title compound was synthesized in the same conditions, described in the example of obtaining compounds 1h-2-4 (synthesis scheme 2), except that compound 5d-0-19 was used instead of compound 4A-0-4.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): of 2.15 (3H, s)to 2.46 (3H, s), 3,93 (2H, s), 6,10 (2H, users), 6,27 (1H, DD, J=5,1 Hz), 7,31 (1H, t, J=4,7 Hz), 7,58 (1H, d, J=5,1 Hz), 7,82 (1H, s), 8,66 (2H, d, J=8,66 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 393 (M+H).

Compound 1h-2-me:

3-(2-Amino-3-herperidin-4-ylmethyl)-4-ethyl-6-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that compound 5d-0-me was used instead of compound 4A-0-4.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 1,06 (3H, ushort, J=7,4 Hz)of 2.16 (3H, s), 2,89 (2H, userc, J=7,4 Hz), 3,91 (2H, s), 6,12 (2H, s), of 6.26 (1H, t, J=5,1 Hz), 7,28-7,37 (3H, m), 7,58 (1H, d, J=5,1 Hz), 7,83 (1H, s), 8,67 (2H, d, J=4,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 407 (M+H).

Compound 1h-2-45:

4-Methyl-3-(2-aminobenzyl)-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that the connection is of 4A-0-45 was used instead of compound 4A-0-4.

1H NMR (Bruker 300 MHz, CDCl3) δ (ppm): 8,59 (2H, d, J=4.6 Hz), 7,69 (1H, d, J=8,8 Hz), 7,24 (1H, d, J=2.3 Hz), 7,18 (1H, DD, J=2.3 Hz, 8,8 Hz), 7,11 (1H, t, J=4,8 Hz), 7,03 (1H, t, J=7.4 Hz), 6,97 (1H, d, J=7,2 Hz), 6,69 (2H, d, J=7,2 Hz), to 3.92 (2H, s), 2.49 USD (3H, s).

Compound 1h-2-46:

4-Methyl-3-(4-aminobenzyl)-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that compound 4A-0-46 was used instead of compound 4A-0-4.

1H NMR (Bruker 300 MHz, CDCl3) δ (ppm): 8,59 (2H, d, J=5.0 Hz), to 7.67 (1H, d, J=8,8 Hz), 7,22 (1H, d, J=2.3 Hz), to 7.15 (1H, DD, J=2.3 Hz, 8,8 Hz), 7,10 (1H, t, J=5.0 Hz), 7,05 (2H, d, J=8,4 Hz), is 6.61 (2H, d, J=8,4 Hz), and 5.30 (2H, s), of 3.95 (2H, s), a 2.45 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 359,99 (M+H).

Compound 1h-2-47:

3-(3-Aminobenzyl)-4-hydroxy-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-2-47 used instead of compound 1g-1-5.

1H-NMR (CD3OD, 270 MHz) δ (ppm): 8,54 (d, 2H, J=4,9 Hz), 7,94 (d, 1H, J=8,4 Hz), 7,32-7,25 (m, 2H), 7,20-7,10 (m, 4H), 7,02 (m, 1H), with 3.89 (s, 2H).

ESIMC m/z: 362 (M+H).

Compound 1h-2-51:

3-(3-Aminophenylamino)-4-methyl-7-(pyrimidine-2-yloxy)-2-OK what about-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that compound 4A-0-51 was used instead of compound 4A-0-4.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 8,69 (d, 2H, J=4,8 Hz), 7,81 (d, 1H, J=8.6 Hz), 7,38 (d, 1H, J=2.1 Hz), 7,33 (t, 1H, J=4,8 Hz), 7,29-7,24 (m, 2H), 6,80 (t, 1H, J=7,7 Hz), 6,00 (m, 2H), 5,86 (s, 1H), a 4.86 (s, 2H), 2.26 and (s, 3H).

ESIMC m/z: 361 (M+H).

Compound 1h-2-52:

3-(3-Aminophenoxy)-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that compound 5d-0-52 was used instead of compound 4A-0-4.

1H-NMR (CDCl3, 300 MHz) δ (ppm): 8,61 (1H, d, J=5.0 Hz), to 7.68 (1H, d, J=8,4 Hz), 7,28 (1H, d, J=2.3 Hz), 7,24 (1H, DD, J=2.3 Hz, J=8,4 Hz), 7,12 (1H, m), 7,06 (1H, m), 6,38 (1H, m), 6,33 (2H, m), of 3.69 (2H, s), 2.40 a (3N with).

MS (ESI+) m/z: 361,99 (M+H).

Compound 1h-2-53:

3-(3-Aminophenoxy)-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that compound 5d-0-53 used instead of the soybean is inane 4A-0-4.

1H-NMR (CDCl3, 300 MHz) δ (ppm): 8,61 (2H, d, J=4.6 Hz), of 7.75 (1H, d, J=8,8 Hz), 7,26 (1H, m), 7,21 (1H, DD, J=2.3 Hz, J=8,8 Hz), 7,13 (1H, m),? 7.04 baby mortality (1H, m), only 6.64 (1H, m), to 6.57 (1H, m), 6,50 (1H, m), 3,66 (2H, user. C)was 2.76 (3H, s).

MS (ESI+) m/z: 377,98 (M+H).

Compound 1h-2-74:

3-(2-Aminothiazol-4-ylmethyl)-7-(pyrimidine-2-yloxy)-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized using compound 5d-0-74 in the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2).

1H NMR (Bruker, (ARX-300), DMSO-d6) δ (ppm): 8,68 (2H, d, J=4.5 Hz), 7,88 (1H, d, J=8,4 Hz), 7,35-7,31 (2H, m), 7,24 (1H, DD, J=9,O Hz, J=2.4 Hz), 6,83 (2H, s), 6,10 (1H, s), with 3.79 (2H, s), 2,47 (3H, s).

Compound 1h-3-1:

4-Methyl-3-(3-aminobenzyl)-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 58

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-3-1 was used instead of compound 1g-1-5.

1H-NMR (CDCl3, 270 MHz) δ (ppm): to 2.46 (3H, s), of 4.00 (2H, s), 6,50 is 6.67 (3H, m), 6,92 (1H, d, J=3.8 Hz), 7,05 (1H, DD, J=7,8, and 7.8 Hz), 7,21-7,33 (3H, m), of 7.64 (1H, d, J=8,9 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 365 (M+H).

Compound 1h-3-3:

4-Methyl-3-(3-aminobenzyl)-7-(thiazol-2-yloxy)-6-chloro-2-oxo-2H-1-benzop is an

Chemical formula 59

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-3-3 was used instead of compound 1g-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,45 (3H, s), 3,83 (2H, s), 4,96 (2H, users), 6,35-6,37 (3H, m), 6,86-6,92 (1H, m), 7,28 (1H, d, J=3.6 Hz), 7,32 (1H, d, J=3.6 Hz), 7,73 (1H, s), of 8.09 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 399 (M+H).

Compound 1h-3-4:

4-Methyl-3-(2-fluoro-3-aminobenzyl)-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 60

The scheme of synthesis 1

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-3-4 was used instead of compound 1g-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,44 (3H, s)to 3.92 (2H?C)6,24 (1H, DDD, J=1,5, 7,0 Hz, JHF=7,0 Hz), is 6.61 (1H, DDD, J=1,5, 8,3 Hz, JHF=8,3 Hz), 6,72 (1H, DD, J=7,0, 8,3 Hz), 7,34-7,38 (4H, m), 7,49 (1H, d, J=2.5 Hz), 7,92 (1H, d, J=8,9 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 383 (M+H).

Compound 1h-3-8:

4-Methyl-3-(3-aminobenzyl)-7-(thiazol-2-yloxy)-6-methyl-2-oxo-2H-1-benzopyran

Chemical formula 61

Specified in zag is lowke compound was synthesized in the same conditions, described in the example of obtaining compounds 1h-1-5, except that compound 1g-3-8 was used instead of compound 1g-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): of 2.27 (3H, s), a 2.45 (3H, s), a-3.84 (2H, s), equal to 4.97 (2H, s), 6,33-6,40 (3H, m), 6.90 to (1H, DD, J=8,2, 8,2 Hz), 7,27-7,31 (2H, m), 7,44 (1H, s), to 7.84 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 379 (M+H).

Compound 1h-3-19:

3-(2-Amino-3-herperidin-4-ylmethyl)-4,6-dimethyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that compound 5d-0-19 was used instead of compound 4A-0-4.

1H-NMR (CDCl3, 270 MHz) δ (ppm): 7,87 (1H, s), 7,58 (1H, d, J=4,8 Hz), 7,45 (1H, s), 7,35-of 7.25 (2H, m), 6,27 (1H, DD, J=4,8 Hz), 6,10 (2H, users), 3,93 (2H, s)to 2.46 (3H, s), of 2.28 (3H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 398 (M+H).

Compound 1h-2A-4:

3-{2-Fluoro-3-aminobenzyl}-4-methyl-7-(5-ftorpirimidinu-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that 2-chloro-5-ftorpirimidinu used instead of 2-bromopyrimidine.

1H YAM who (Bruker, 300 MHz, CDCl3) δ (ppm): 8,44 (2H, s), of 7.69 (1H, d, J=8,8 Hz), 7,21 (1H, d, J=2.7 Hz), 7,14 (1H, DD, J=2.3 Hz, 8,8 Hz), for 6.81 (1H, m), 6,63 (1H, m), 6,55 (1H, m)4,06 (2H, s), 3,70 (2H, s), is 2.44 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 395,85 (M+H).

Compound 1h-2b-4:

3-{2-Fluoro-3-aminobenzyl}-4-methyl-7-(4-chloropyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that 2,4-dichloropyrimidine used instead of 2-bromopyrimidine.

1H NMR (Bruker 300 MHz, CDCl3) δ (ppm): 8,51 (1H, d, J=5.7 Hz), 7,69 (1H, d, J=8,8 Hz), 7,18 (1H, d, J=2.7 Hz), 7,13 (1H, DD, J=2.3 Hz, 8,8 Hz), 6,92 (1H, d, J=5.7 Hz), PC 6.82 (1H, m), only 6.64 (1H, m), to 6.57 (1H, m), 4,07 (2H, s), 3,71 (2N with), the 2.46 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 411,75 (M), 413,80 (M+2).

Compound 1h-5-4:

3-{2-Fluoro-3-aminobenzyl}-4-methyl-7-(2,4-dimethoxypyrimidine-6-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that 6-chloro-2,4-dimethoxypyrimidine used instead of 2-bromopyrimidine.

1H NMR (Bruker 300 MHz, CDCl3) δ (ppm): to 7.64 (1H, d, J=8,8 Hz), to 7.15 (1H, d, J=2.7 Hz), to 7.09 (1H, DD, J=2.3 Hz, J=8,8 Hz), for 6.81 (1H, m), only 6.64 (1H, m), to 6.57 (1H, m), 5,86 (1H, s), of 4.05 (2H, s), of 3.97 (3H, s)to 3.89 (3H, s), 3,70 (2H, Sirs), of 2.44 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 438,06 (M+H).

Compound 1h-3A-4:

3-(2-Fluoro-3-aminobenzyl)-4-methyl-7-(benzothiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-3-4 (synthesis scheme 2), except that 2-chlorobenzothiazole used instead of 2-bromothiazole.

1H NMR (Bruker 300 MHz, CDCl3) δ (ppm): 7,72 (3H, m), 7,47 (1H, d, J=2.7 Hz), 7,42 (1H, m), 7,32 (2H, m), PC 6.82 (1H, m), only 6.64 (1H, m), to 6.57 (1H, m), 4,07 (2H, s), 3,70 (2H, s), a 2.45 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 433,00 (M+H).

Compound 1h-1A-4:

4-Methyl-3-(2-fluoro-3-aminobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylthiocarbamyl acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-3-4 (synthesis scheme 2), except that dimethylthiocarbamate used instead of 2-bromothiazole.

1H NMR (Bruker 300 MHz, CDCl3) δ (ppm): to 7.64 (1H, d, J=9.5 Hz), 7,06 (1H, s),? 7.04 baby mortality (1H, DD, J=2.3 Hz, J=8.0 Hz), for 6.81 (1H, m), 6,63 (1H, m), 6,55 (1H, m), of 4.05 (2H, s), 3,70 (2H, s), 3,47 (3H, s)to 3.38 (3H, s), 2,43 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 387,04 (M+H).

Compound 1h-3b-4:

3-(2-Fluoro-3-aminobenzyl)-4-methyl-7-(5-bromothiazole-2-yloxy)-2-oxo-2H-1-benzopyran

p> Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-3-4 (synthesis scheme 2), except that 2,5-dibromothiazole used instead of 2-bromothiazole.

1H NMR (Bruker 300 MHz, CDCl3) δ (ppm): 7,66 (1H, d, J=8,8 Hz), 7,29 (1H, d, J=2.7 Hz), 7,21 (1H, DD, J=2.7 Hz, J=9.7 Hz), 7,19 (1H, s), for 6.81 (1H, m), 6,63 (1H, m), 6,55 (1H, m), of 4.05 (2H, s), 3,70 (2H, s), 2,43 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 460,67 (M),462,75 (M+2).

Compound 1h-2A-16:

4-Methyl-3-(3-fluoro-2-aminopyridine-4-ylmethyl)-7-(5-ftorpirimidinu-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that compound 5d-0-16 was used instead of compound 4A-0-4 and 2-chloro-5-ftorpirimidinu used instead of 2-bromopyrimidine.

1H NMR (Bruker 300 MHz, CDCl3) δ (ppm): 8,44 (2H, s), 7,71 (1H, d, J=5.3 Hz), 7,69 (1H, d, J=8,4 Hz), 7,22 (1H, d, J=1.9 Hz), 7,16 (1H, DD, J=1.9 Hz, J=8,4 Hz), 6,50 (1H, m), 4,55 (2H, users), of 4.05 (2H, s), 2,43 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 396,98 (M+H).

Compound 1h-2b-16:

4-Methyl-3-(3-fluoro-2-aminopyridine-4-ylmethyl)-7-(4-chloropyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example getting connected 1-2-4 (synthesis scheme 2), except that compound 5d-0-16 was used instead of compound 4A-0-4 and 2,4-dichloropyrimidine used instead of 2-bromopyrimidine.

1H NMR (Bruker 300 MHz, CDCl3) δ (ppm): charged 8.52 (1H, d, J=5.3 Hz), 7,73 (1H, d, J=1.9 Hz), 7,71 (1H, d, J=5.3 Hz), 7,21 (1H, d, J=2.7 Hz), to 7.15 (1H, DD, J=1.9 Hz, J=8,4 Hz), 6,93 (1H, d, J=5.7 Hz), 6,53 (1H, m), of 4.57 (2H, users), 4,06 (2N with), the 2.46 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 412,98 (M), 414,95 (M+2).

Compound 1h-5-16:

4-Methyl-3-(3-fluoro-2-aminopyridine-4-ylmethyl)-7-(2,4-dimethoxypyrimidine-6-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that compound 5d-0-16 was used instead of compound 4A-0-4 and 2,4-dimethoxy-6-chloropyrimidine used instead of 2-bromopyrimidine.

1H NMR (Bruker 300 MHz, CDCl3) δ (ppm): 7,72 (1H, d, J=5.3 Hz), the 7.65 (1H, d, J=8,8 Hz), 7,17 (1H, d, J=2.3 Hz), 7,12 (1H, DD, J=2.3 Hz, J=8,8 Hz), of 6.52 (1H, m), by 5.87 (1H, s), of 4.57 (2H, users), Android 4.04 (2H, s), 3,98 (3H, s)to 3.89 (3H, s)that is 2.44 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 439,02 (M+H).

Compound 1h-3A-16:

4-Methyl-3-(3-fluoro-2-aminopyridine-4-ylmethyl)-7-(benzothiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-2-4 (scheme Shin is ESA 2), except that compound 5d-0-16 was used instead of compound 4A-0-4 and 2-chlorobenzothiazole used instead of 2-bromopyrimidine.

1H NMR (Bruker 300 MHz, CDCl3) δ (ppm): 7,73 (4H, m)to 7.50 (1H, d, J=2.3 Hz), the 7.43 (1H, m), of 7.36 (1H, DD, J=2.7, and an 8.8 Hz), 7,33 (1H, m), 6,51 (1H, m), 4,58 (2H, user. C)of 4.05 (2H, s)to 2.46 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 433,96 (M+H).

Compound 1h-3b-16:

4-Methyl-3-(3-fluoro-2-aminopyridine-4-ylmethyl)-7-(5-bromothiazole-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that compound 5d-0-16 was used instead of compound 4A-0-4 and 2.5-dibromothiazole used instead of 2-bromopyrimidine.

1H NMR (Bruker 300 MHz, CDCl3) δ (ppm): 7,71 (1H, d, J=5.3 Hz), to 7.68 (1H, d, J=8,8 Hz), 7,31 (1H, d, J=2.3 Hz), 7,24 (1H, DD, J=2.7 Hz, J=8,8 Hz), 7,20 (1H, s), 6,50 (1H, m), 4,56 (2H, s), Android 4.04 (2H, s), is 2.44 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 461,90 (M), 463,90 (M+2).

Compound 1h-1A-16:

2-Oxo-2H-3-(2-amino-3-herperidin-4-ylmethyl)-4-methyl-1-benzopyran-7-silt ether dimethylthiocarbamyl acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that compound 5d-0-16 ispolzovalist compound 4A-0-4 and dimethylthiocarbamate used instead of 2-bromopyrimidine.

1H NMR (Bruker 300 MHz, CDCl3) δ (ppm): 7,71 (1H, d, J=5.3 Hz), the 7.65 (1H, d, J=9,2 Hz), was 7.08 (1H, s), 7,06 (1H, d, J=4.6 Hz), 6,50 (1H, m), 4,55 (2H, users), Android 4.04 (2H, s), 3,47 (3H, s)to 3.38 (3H, s), 2,43 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 388,00 (M+H).

Compound 1h-1b-1:

3-(3-Aminobenzyl)-7-isobutoxy-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-1b-1 was used instead of compound 1g-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 0,98 (3H, s), and 1.00 (3H, s), 1,95-2,12 (1H, m), 2,39 (3 H, s), with 3.79 (2H, s), 3,86 (2H, d, J=6.5 Hz), 4,96 (2H, users), 6,32-6,41 (3H, m), 6,82-to 7.00 (3H, m), 7,72 (1H, d, J=9.5 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 338 (M+H).

Compound 1h-1C-1:

3-(3-Aminobenzyl)-7-(2-floratone)-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-1s-1 was used instead of compound 1g-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,40 (3H, s), 3,80 (2H, s), 4,27-4,32 (1H, m), 4,37 is 4.45 (1H, m), 4,66-4,71 (1H, m), 4,84-4,89 (1H, m), 4,96 (2H, users), 6,32-to 6.39 (3H, m), 6.90 to (1H, DD, J=8,6, and 7.3 Hz), of 6.96-7,07 (2H, m), 7,75 (1H, d, J=8.6 Hz).

ESI (LC/MS in the registration mode, the positive charger, side buttons is the R ions) m/z: 328 (M+H).

Compound 1h-1s-3:

3-(3-Aminobenzyl)-6-chloro-7-(2-floratone)-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-1s-3 was used instead of compound 1g-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.41 (3H, s), 3,80 (2H, s), 4,36-4,43 (1H, m), 4,46-of 4.54 (1H, m), 4,68-of 4.75 (1H, m), 4,86-is 4.93 (1H, m), 4,96 (2H, users), 6,32-to 6.39 (3H, m), 6.90 to (1H, DD, J=8,6, 7,0 Hz), 7,29 (1H, s), of 7.90 (1H, C).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 362 (M+H).

Compound 1h-11-3:

4-Methyl-3-(3-aminobenzyl)-7-(thiophene-3-yl)-6-chloro-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-11-3 used instead of compound 1g-1-5.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): to 7.68 (1H, s), EUR 7.57 (1H, DD, J=3,05 Hz, J=1,14 Hz), 7,34-7,39 (2H, m), 7,35 (1H, DD, J=3,82 Hz, J=1,14 Hz), 7,06 (1H, t, J=8,01 Hz), only 6.64 (1H, d, J=8,01 Hz), 6,60 (1H, s), 6,53 (1H, DD, J=7,63 Hz, J=1,53 Hz)to 3.99 (2H, s), is 2.44 (3H, s), and 2.27 (2H, usher.).

Compound 1h-12-1:

4-Methyl-3-(3-aminobenzyl)-7-(pyridin-4-yl)-2-oxo-2H-1-benzopyran

2 ml of a mixture of the Meon and H2O (9:1), zinc metal (81 mg, 1,mmol) and ammonium chloride (20 mg, 1.6 mmol) was added to the compound 1g-12-1 (23 mg, holding 0.062 mmol) and the resulting mixture was stirred at room temperature for 2 days. Then it was purified by chromatography on silica gel (mixture of methylene chloride:methanol = 30:1) to obtain the specified title compound (15 mg, 73%).

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 8,72 (2H, d, J=6,10 Hz), 7,73 (1H, d, J=8,01 Hz), to 7.59-7,53 (4H, m), 7,06 (1H, t, J=7,63 Hz), of 6.66 (1H, d, J=7,63 Hz), 6,62 (1H, s), 6,53 (1H, DD, J=7,63 Hz, J=2,29 Hz)to 4.01 (2H, s), 2.49 USD (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 343,40 (M+1).

Compound 1h-16-1:

4-Methyl-3-(3-aminobenzyl)-7-(thiazol-5-yl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-16-1 was used instead of compound 1g-1-5.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 8,82 (Ls, C), 8,18 (1H, s), to 7.64 (1H, d, J=8,01 Hz), 7,52 (1H, s)to 7.50 (1H, d, J=8,39 Hz), 7,09 (Ls, t, J=7,63 Hz), of 6.66 (1H, d, J=7,63 Hz), 6,62 (1H, s), 6,53 (1H, d, J=7,63 Hz)to 3.99 (2H, s), the 2.46 (3H, s).

Compound 1h-17-1:

4-Methyl-3-(3-aminobenzyl)-7-(thiazol-2-yl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-17-1 was used instead of compound 1g-1-5./p>

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 8,02 (1H, d, J=3,05 Hz), 7,94 (2H, s), to $ 7.91 (1H, d, J=3,43 Hz), of 7.90 (1H, s)6,91 (1H, t, J=8,01 Hz), 6,40-6,36 (3H, m), of 4.95 (2H, s), 3,86 (2H, s), 2,47 (3H, s).

Compound 1h-18-1:

4-Methyl-3-(3-aminobenzyl)-7-(pyridin-3-yl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-12-1, except that the compound 1g-18-1 was used instead of compound 1g-12-1.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 8,89 (1H, d, J=1,91 Hz), 8,66 (1H, DD, J=4,96 Hz, J=1,53 Hz), 7,92 (1H, dt, J=8,01 Hz, J=1,91 Hz), 7,72 (1H, d, J=8,01 Hz), 7,54-7,51 (2H, m), 7,42 (1H, DD, J=7,63 Hz, J=0,30 Hz), 7,06 (1H, t, J=8,01 Hz), of 6.66 (1H, d, J=8,01 Hz), 6,62 (1H, s), of 6.52 (1H, DD, J=8,01 Hz, J=1,91 Hz)to 4.01 (2H, s), 2.49 USD (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 343,27 (M+1).

Compound 1h-19-3:

4-Methyl-3-(3-aminobenzyl)-6-chloro-7-(3-methoxyphenyl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-19-3 used instead of compound 1g-1-5.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): of 7.69 (1H, s), 7,38 (1H, t, J=7,63 Hz), 7,32 (1H, s), 7,09-of 6.96 (4H, m), only 6.64 (1H, d, J=7,25 Hz), 6,60 (1H, s), of 6.52 (1H, DD, J=8,01 Hz, J=2,29 Hz)to 3.99 (2H, s), a 3.87 (3H, s), 3,62 (2H, user. C)to 2.46 (3H, s).

Compound 1h-21-3:

4-Methyl-3-(3-aminobenzyl)-6-chloro-7-(5-acetylthiophene-2-yl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 1g-21-3 used instead of compound 1g-1-5.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 8,79 (2H, d, J=4,96 Hz), 8,17 (1H, s), 7,73 (1H, s), 7,46 (1H, t), 7,13 (2H, m), of 6.96 (1H, d, J=7,63 Hz)4,06 (2H, s), 2,60 (3H, s)to 2.41 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 424,09 (M+H).

Compound 1h-22-1:

4-Methyl-3-(3-aminobenzyl)-7-(3-acetylphenyl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-12-1, except that the compound 1g-22-1 was used instead of compound 1g-12-1.

1H-NMR (Bruker (ARX-300), 300 MHz, DMSO-d6) δ (ppm): 8,23 (1H, t), with 8.05 (1H, d, J=8,01 Hz), 7,95 (1H, d, J=8,39 Hz), to 7.84 (1H, d, J=1,53 Hz), 7,78 (1H, DD, J=8,01 Hz), the 7.65 (2H, t)6,91 (1H, t), to 6.43 (3H, m), to 4.98 (2H, s), 3,85 (2H, s), 2,71 (3H, C)of 2.50 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 384,35 (M+1).

Compound 1h-23-1:

4-Methyl-3-(3-aminobenzyl)-7-(4-acetylphenyl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-12-1, except that what about that what connection 1g-23-1 was used instead of compound 1g-12-1.

MS (Micromass, Quattromicro, ESI+) m/z: 413,27 (M+Na).

Compound 1h-1E-1:

4-Methyl-3-(3-aminobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether triftormetilfullerenov acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-12-1, except that the compound 1g-1E-1 was used instead of compound 1g-12-1.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): to 7.67 (1H, d, J=8,77 Hz), 7,22 (2H, m), 7,05 (1H, t), 6,59 (3H, t,d, J=8,39 Hz), from 5.29 (1H, s), was 4.02 (2H, s)to 2.46 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 414,10 (M+1).

Compound 1g-28-1:

4-Methyl-3-(3-aminobenzyl)-7-(4-N,N-dimethylaminophenyl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-12-1, except that the compound 1g-28-1 was used instead of compound 1g-12-1.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): the 7.65 (5H, m), 6,63 (2H, d, J=8,77 Hz), of 6.65 (2H, d, J=8,39 Hz), 6,53 (2H, DD, J=8.6 Hz), was 4.02 (2H, s)to 3.64 (2H, users), 3,15 (6N, (C), 2,43 (3H, s).

Compound 1j-1-5-1:

3-{2-Fluoro-3-(aminosulfonyl)aminobenzyl}-6-fluoro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 62

Formic acid (754 μl, 10.0 mmol) was added to chlorosulfonylisocyanate (1,74 ml, 20.0 mmol) at 0°C and the mixture was stirred at room temperature for 1 h Then to the mixture was added dichloromethane (10 ml) and the mixture was additionally stirred for 2 hours the solution (3,71 ml) was added to a solution of compound 1h-1-5 (2,88 g, 7,42 mmol) and pyridine (1,21 ml, 15 mmol) in dichloromethane (50 ml) and the mixture was stirred at room temperature for 16 hours Then the reaction solution was added the ethyl acetate and the solution was washed with sodium carbonate solution and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate and the solvent is kept at reduced pressure. The obtained residue was purified column chromatography on silica gel with obtaining specified in the title compound (680 mg, 20%).

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.42 (3H, s)to 2.94 (3H, s), is 3.08 (3H, s), of 3.97 (2H, s), at 6.84 (1H, m), 7,00 (Ls, DD, J=7,8, and 7.8 Hz), 7,10 (2H, users), 7,33 (1H, m), of 7.48 (1H, d, J=6.8 Hz), 7,86 (1H, d, J=11,4 Hz), 9,12 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 468 (M+2H-Na).

Compound 1j-1-5-1Na:

3-{2-Fluoro-3-(aminosulfonyl)aminobenzyl}-6-fluoro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid sodium salt

Chemical formula 63

One equivalent of a solution g is droxia sodium in methanol was added dropwise at room temperature to a mixture of compound 1j-1-5-1 and methylene chloride. After 30 min the solvent drove with obtaining specified in the connection header.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,39 (3H, s)to 2.94 (3H, s)to 3.09 (3H, s), 3,88 (2H, s), 5,43 (1H, users), 6,21 (1H, m), to 6.67 (1H, m), 7,19 (1H, m), the 7.43 (1H, d, J=6.8 Hz), 7,83 (1H, d, J=11.2 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 468 (M+2H - Na).

Compound 1j-1-5-1K:

3-{2-Fluoro-3-(aminosulfonyl)aminobenzyl}-6-fluoro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid potassium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that KOH was used instead of NaOH.

1H NMR (CD3OD) δ (ppm): to 7.67 (1,0N, d, J=11,0 Hz), 7,40-of 7.25 (2H, m), 6,88 (1,0N, t, J=7.9 Hz), 6,64 (1,0N, t, J=7.9 Hz), 4.04 the (2,0N,) and 3.15 (3H, s), 3,03 (3H, s), is 2.44 (3H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 468 (M+2H-K).

Compound 1j-1-1-1:

3-{3-(Aminosulfonyl)aminobenzyl}-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 64

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that the compound 1h-1-1 was used instead of compound 1h-1-5.

1H-NMR (DCl 3, 270 MHz) δ (ppm): 2,43 (3H, s), to 3.02 (3H, s), of 3.12 (3H, s), 3,98 (2H, s), 6.87 in-to 7.09 (5H, m), 7,18 (1H, DD, J=8.1 Hz), 7,60 (1H, d, J=8,1 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 432 (M+H).

Compound 1j-1-2-1:

3-{3-(Aminosulfonyl)aminobenzyl}-6-fluoro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 65

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that the compound 1h-1-2 was used instead of compound 1h-1-5.

1H NMR (CD3OD, 270 MHz) δ (ppm): to 2.46 (3H, s), a 3.01 (3H, s)and 3.15 (3H, s); was 4.02 (2H, s), to 6.95 (1H, d, J=7,3 Hz), 7,06-7,22 (3H, m), 7,27 (1H, d, J=6.8 Hz), to 7.64 (1H, d, J=11,1 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 450 (M+H).

Compound 1j-1-3-1:

3-{3-(Aminosulfonyl)aminobenzyl}-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 66

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that the compound 1h-1-3 was used instead of compound 1h-1-5.

lH-NMR (CDCl3, 270 MHz) δ (ppm) : to 2.42 (3H, s), 3,05 (3H, s), up 3.22 (3H, s), of 3.95 (2H, s), 6,80-7,20 (4H, m), 7,25 (1H, s), 7,60 (1H, s).

ESI (LC/MS in the dir the IU register positively charged ions) m/z: 466 (M+H).

Compound 1j-1-4-1:

3(3-Aminosulfonyl-2-terbisil)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 67

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that the compound 1h-1-4 was used instead of compound 1h-1-5.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 2,44 (3H, s), with 2.93 (3H, s), of 3.07 (3H, s), of 3.97 (2H, s), PC 6.82 (1H, ushort, J=8.6 Hz), 6,99 (1H, ushort, J=8.6 Hz), 7,19 (1H, DD, J=8,9, and 2.3 Hz), 7, 25 (1H, d, J=2.3 Hz), 7,33 (1H, ushort, J=8.6 Hz), 7,86 (1H, d, J=8,9 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 450 (M+H).

Compound 1j-1-4-1Na:

3-{3-(Aminosulfonyl)amino-2-terbisil}-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid sodium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-1-4-1 was used instead of compound 1j-1-5-1.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): to 2.41 (3H, s), with 2.93 (3H, s), of 3.07 (3H, s), 3,88 (2H, s), 6,18-6,23 (1H, m), to 6.67 (1H, DD, J=7,6, 7.9 Hz), 7,14-7,22 (2H, m), 7,24 (1H, d, J=2.3 Hz), 7,83 (1H, d, J=8.6 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 450 (M+2H-Na).

Compound 1j-1-7-1:

3-{3-(Aminosulfonyl)aminobenzyl}-6-iodine-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 68

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that the compound 1h-1-7 was used instead of compound 1h-1-5.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 2,45 (3H, s), 2,96 (3H, s), of 3.13 (3H, s), 3,93 (2H, s), 6,83 (1H, d, J=8.1 Hz), 6,94 (1H, s), 7,02-7,05 (2H, m), 7,16 (1H, DD, J=8,1, 8.1 Hz), 7,38 (1H, s), 8,24 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 558 (M+H).

Compound 1j-1-7-1Na:

3-{3-(Sulfanilamide)benzyl}-6-iodine-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid sodium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-1-7-1 was used instead of compound 1j-1-5-1.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 2,44 (3H, s), 2,96 (3H, s), of 3.13 (3H, s), 3,83 (2H, s), 6,36 (1H, d, J=7,6 Hz), of 6.68 (1H, s), 6,77 (1H, d, J=7.9 Hz), to 6.88 (1H, DD, J=7,6, 7.9 Hz), 7,35 (1H, s), to 8.20 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 558 (M+2H-Na).

Compound 1j-1-7-1K:

3-{3-(Sulfanilamide)benzyl}-6-iodine-4-methyl-2-oxo-2H-1-benzopyran-7-and the new ether dimethylcarbinol acid potassium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-1-7-1 was used instead of compound 1j-1-5-1 and KOH was used instead of NaOH.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 2,45 (3H, s), 2,96 (3H, s), of 3.13 (3H, s), 3,85 (2H, s), 6.48 in (1H, d, J=7.8 Hz), 6,74 (1H, s), 6,83 (1H, d, J=7,6 Hz), to 6.95 (1H, DD, J=7,6, and 7.8 Hz), was 7.36 (1H, s), 8,21 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 558 (M+2H - K).

Compound 1j-1-8-1:

3-{3-(Aminosulfonyl)aminobenzyl}-6-methyl-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 69

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that the compound 1h-1-8 was used instead of compound 1h-1-5.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 2,22 (3H, s), a 2.45 (3H, s)to 2.94 (3H, s)to 3.09 (3H, s), 3,93 (2H, s), 6,83 (1H, d, J=8.1 Hz), to 6.95 (1H, s), 7,02-7,05 (2H, m), 7,16 (1H, DD, J=8,1, 8.1 Hz), 7,21 (1H, s), of 7.75 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 446 (M+H).

Compound 1j-1-9-1:

3-{3-(Aminosulfonyl)aminobenzyl}-6-cyano-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 70

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that the compound 1h-1-9 was used instead of compound 1h-1-5.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 2,97 (3H, s), of 3.12 (3H, s), of 3.94 (2H, s), at 6.84 (1H, d, J=8.1 Hz), 6,97 (1H, s), 7,02-7,05 (2H, m), 7,16 (1H, DD, J=8,1, 8.1 Hz), 7,60 (1H, s), 8,46 (1H, s).

One of the peaks of CH3overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 457 (M+H).

Compound 1j-1-4-1F:

3-(3-Aminosulfonyl-2-terbisil)-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 71

Chlorosulfonylisocyanate (0,150 ml) and formic acid (0,065 ml) were mixed at 0°C and the mixture was stirred at room temperature for 1 h To this mixture was added dichloromethane (1.2 ml) and was dissolved and the mixture is additionally stirred at room temperature for 4 h were Selected to 0.060 ml of solution was added at 0°C. to a solution of 3-(3-amino-2-terbisil)-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid (compound 1h-1-4F) of 25.2 mg) in a mixture of dichloromethane (1.0 ml)/pyridine (0,0065 ml) and the mixture was stirred at room temperature for 3 h Then the reaction solution was added a saturated solution of bicarbonate n is sodium and the mixture was extracted with ethyl acetate. The extract was washed with saturated salt solution and the organic layer was dried over anhydrous magnesium sulfate. The solvent is kept under reduced pressure and the obtained residue was purified by thin-layer chromatography on silica gel (Aminogen) (mixture of dichloromethane:methanol = 90:10) to obtain the specified title compound (12.0 mg).

1H-NMR (270 MHz, DMSO-d6) δ (ppm): at 2.93 (3H, s), of 3.07 (3H, s)4,06 (2H, s), of 5.84 (2H, d, J=45,8 Hz), at 6.84 (1H, ushort, J=7,7 Hz), 7,01 (1H, ushort, J=7,7 Hz), 7,12 (1H, users), 7,29-7,40 (2H, m), 7, 92 (1H, DD, J=8,9, and 2.1 Hz)to 9.15 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 468 (M+H).

Compound 1j-1-3-1F-other:

3-{3-((tert-Butoxycarbonyl)aminosulfonyl)aminobenzyl}-6-chloro-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 72

The triethylamine (34 μl, 0.25 mmol) and N-(tert-butoxycarbonyl)-N-{4-(dimethylethanolamine)-1,4-dihydropyridines-1-ylsulphonyl}asanid (49 mg, 0.16 mmol) were added sequentially to a solution of 3-(3-aminobenzyl)-6-chloro-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid (compound 1h-1-3F) (33 mg, 0,082 mmol) in anhydrous dichloromethane (1.0 ml) and the mixture was stirred at room temperature overnight. Then the reaction mixture was poured into water and was extracted with ethyl acetate. Organic is xtract washed with saturated salt solution and dried over magnesium sulfate. Then the crude solid was obtained by concentration in vacuo and was purified preparative TLC (mixture of ethyl acetate:hexane = 1:2) to obtain the specified title compound (30 mg, 63%) as a white powder.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 8,07 (s, 1 H), 7,56 (s, 1H), 7,20-to 6.80 (m, 6H), 5,86 (d, J=46.2 Hz, 2H), a 4.03 (s, 2H), 3,11 (s, 3H), 2.95 and (s, 3H), of 1.29 (s, 9H).

ESIMC m/z: 528 (M-tBu+2N).

Compound 1j-1-3-1F:

3-{3-(Aminosulfonyl)aminobenzyl}-6-chloro-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 73

Triperoxonane acid (0.1 ml) was added to a solution of 3-{3-((tert-butoxycarbonyl)aminosulfonyl)aminobenzyl}-6-chloro-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid (compound 1j-1-3-1F-other) (23 mg, 0,039 mmol) in anhydrous dichloromethane (1.0 ml) and the mixture was stirred at room temperature for 3 h Then the reaction mixture was poured into saturated sodium bicarbonate solution and was extracted with ethyl acetate. The organic extract was washed with saturated salt solution and dried over magnesium sulfate. The crude solid was obtained by concentration in vacuo and was purified preparative TLC (mixture of ethyl acetate:hexane = 1:1) to obtain the specified title compound (19 mg, 100%) as a pale yellow powder.

1H-NMR (270 MHz,DMSO-d 6) δ (ppm): 9,40 (users, 1H), 8,07 (s, 1H), 7,56 (s, 1H), 7,17 (t, J=8.0 Hz, 1H), 7,05 (C+d, 3H), of 6.96 (s, 1H), PC 6.82 (d, J=7,3 Hz, 1H), 5,86 (d, J=46.2 Hz, 2H), a 4.03 (s, 2H), 3,11 (s, 3H), 2.95 and (s, 3H).

ESIMC m/z: 484 (M+H).

Compound 1j-1-1-1F:

3-{3-(Aminosulfonyl)aminobenzyl}-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 74

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that the compound 1h-1-1F was used instead of compound 1h-1-5.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): at 2.93 (3H, s), of 3.07 (3H, s), was 4.02 (2H, s), of 5.83 (2H, d, J=46,0 Hz), for 6.81 (1H, userd, J=7,4 Hz), of 6.96 (1H, users), 7,05 (3H, m), to 7.15 (1H, d, J=7,6 Hz), 7,22 (1H, DD, J=8,7, and 2.3 Hz), 7,30 (1H, d, J=2,3 Hz), to $ 7.91 (1H, DD, J=8,7, and 2.3 Hz), 9,39 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 450 (M+H).

Compound 1j-1-2-1F:

3-{3-(Aminosulfonyl)aminobenzyl}-6-fluoro-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 75

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that the compound 1h-1-2F was used instead of compound 1h-1-5.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): to 2.94 (3H, s)to 3.09 (3H, s), a 4.03 (2H, s), of 5.82(2H, d, J=46,0 Hz), for 6.81 (1H, d, J=8.1 Hz), of 6.96 (1H, s), 7,05 (2H, m), 7,17 (1H, t, J=7,7 Hz), 7,54 (1H, d, J=6.9 Hz), 7,89 (1H, d, J=9.7 Hz), 9,36 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 468 (M+H).

Compound 1j-1-3-home:

3-{3-(Aminosulfonyl)aminobenzyl}-6-chloro-4-methoxymethyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that the compound 7d-1-one was used instead of compound 1h-1-5.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 9,38 (s, 1H), 8,01 (s, 1H), 7,50 (s, 1H), 7,17 (t, 1H, J=8.0 Hz), 7,06-to 6.95 (m, 4H), PC 6.82 (d, 1H, J=7,3 Hz), 4.72 in (s, 2H), 4.00 points (s, 2H), 3,34 (s, 3H), 3,10 (s, 3H), 2.95 and (s, 3H).

ESI m/z: 496 (M+H).

Compound 1j-1-36-1:

3-{(3-Aminosulfonyl)amino-4-terbisil}-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Compound 1j-1-1-1 (300 mg, 0.70 mmol) and N,N-debtor-2,2'-bipyridine bis(tetrafluoroborate) (256 mg, 0.70 mmol) was stirred in acetonitrile at 50°C for 10 hours Specified in the title compound was obtained by chromatography on silica gel using a solvent mixture of ethyl acetate-hexane.

1H-NMR (270 MHz, THF-d8) δ (ppm): 2,96 (3H, s), is 3.08 (3H, s), of 4.00 (2H, s), 6 (2H, usher.), of 6.96 (2H, m), 7,10 (2H, m), 7.5 (d, J=8,2 Hz), 7,72 (1H, d, J=8.6 Hz), 8,30 (1H of usher.).

One of the methyl peaks overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 450 (M+H).

Compound 1j-1-37-1:

3-{(3-Aminosulfonyl)amino-6-terbisil}-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was obtained in the form of a separate faction in the formulation column chromatography of the reaction mixture when the connection 1j-1-36-1.

1H-NMR (270 MHz, CD3OD) δ (ppm): 2,50 (3H, s), 3,03 (3H, s)and 3.15 (3H, s)4,06 (2H, s), of 6.99 (2H, m), 7,20 (3H, m), 7,83 (1H, DD, J=8,6 0,7 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 450 (M+H).

Compound 1j-1-38-1:

3-(3-(Aminosulfonyl)aminobenzyl)-6-carbarnoyl-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that the compound 1h-1-38 used instead of compound 1h-1-5.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 2,90 (3H, s), 3,05 (3H, s), of 3.95 (2H, s), 6,83 (1H, d, J=7,4 Hz), 6,95-was 7.08 (4H, m), 7,17 (1H, DD, J=7,4, 8.1 Hz), 7,29 (1H, s)to 7.50 (1H, users), 7,81 (1H, users), of 8.00 (1H, s), 9,37 (1H, users).

The peak of CH3overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged and the new) m/z: 475 (M+H).

Compound 1j-1-39-1:

3-(3-(Aminosulfonyl)aminobenzyl)-4-methyl-2-oxo-6-trimethylsilylethynyl-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that the compound 1h-1-39 used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 0,23 (9H, s)to 2.46 (3H, s)to 2.94 (3H, s), 3,10 (3H, s), 3,93 (2H, s), 6,83 (1H, d, J=7.8 Hz), 6,93-to 7.09 (4H, m), 7,16 (1H, t, J=7.8 Hz), to 7.15 (1H, s), of 7.70 (1H, s), 9,13 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 528 (M+H).

Compound 1j-1-40-1:

3-(3-(Aminosulfonyl)aminobenzyl)-6-ethinyl-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that the compound 1h-1-40 was used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.46 (3H, s)to 2.94 (3H, s)to 3.09 (3H, s), 3,93 (2H, s), of 4.45 (1H, s), at 6.84 (1H, d, J=7,4 Hz), of 6.96 (1H, s), of 6.96 for 7.12 (3H, m), 7,16 (1H, t, J=7.9 Hz), 7,38 (1H, s), to 7.99 (1H, s), 9,36 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 456 (M+H).

Compound 1j-1-72-1:

3-(3-(Aminosulfonyl)aminobenzyl is)-4-methyl-2-oxo-2H-pyrano[2,3-b]pyridine-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that 3-(3-aminobenzyl)-4-methyl-2-oxo-2H-pyrano[2,3-b]pyridine-7-silt ether dimethylcarbinol acid (compound 1h-1-72) was used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,47 (3H, s), 2,95 (3H, s), 3,06 (3H, s), of 3.94 (2H, s), 6,85 (1H, d, J=7,6 Hz), 6.90 to-7,22 (1H, users), 6,97 (1H, s),? 7.04 baby mortality (1H, d, J=7.8 Hz), 7,17 (1H, DD, J=7,6, and 7.8 Hz), 7,27 (1H, d, J=8,1 Hz), 8,43 (1H, d, J=8,1 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 433 (M+H).

Compound 1j-1d-1-1:

3-(3-(Aminosulfonyl)aminobenzyl)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether pyrrolidin-1-carboxylic acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that the compound 1h-1d-1 was used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 1,84-of 1.94 (4H, m), the 2.46 (3H, s)to 3.36 (2H, t, J=6.6 Hz), 3,52 (2H, t, J=6.6 Hz), 3,93 (2H, s), at 6.84 (1H, d, J=7,3 Hz), 6,94-was 7.08 (4H, m), 7,13-7,21 (2H, m), 7,26 (1H, d, J=2.2 Hz), 7,86 (1H, d, J=8.7 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 458 (M+H).

Compound 1j-2-4-1:

3-{2-Fluoro-3-(aminosulfonyl)aminobenzyl}-4-methyl-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzop the Russian Academy of Sciences

Chemical formula 76

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that the compound 1h-2-4 was used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.46 (3H, s)to 3.99 (2H, s), 6,80-to 6.88 (1H, m), 6,97-7,05 (1H, m), 7,06 (2H, users), 7,28 (1H, DD, J=8,9, and 2.3 Hz), 7,30-7,38 (2H, m), 7,38 (1H, d, J=2.3 Hz), 7,60 (1H, d, J=8,9 Hz), 8,69 (2H, d, J=4,9 Hz), 9,13 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 457 (M+H).

Compound 1j-2-4-1Na:

3-{2-Fluoro-3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran sodium salt

Chemical formula 77

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-2-4-1 was used instead of compound 1j-1-5-1.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,43 (3H, s)to 3.89 (2H, s), 6,12-6,21 (1H, m), 6,60-6,70 (1H, m), 7,13-7,29 (2H, m), 7,33 (1H, t, J=4,8 Hz), was 7.36 (1H, d, J=2.3 Hz), 7,88 (1H, d, J=8,9 Hz), 8,69 (2H, d, J=4,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 457 (M+2H-Na).

Compound 1j-2-4-1K:

3-(3-Sulfanilamide-2-terbisil)-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran potassium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-2-4-1 was used instead of compound 1j-1-5-1 and KOH was used instead of NaOH.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,44 (3H, s), 3,91 (2H, s), 6,27-6,32 (1H, m), of 6.73 (1H, DD, J=7,7, 7.9 Hz), 7.18 in-7,27 (2H, m), 7,33 (1H, t, J=4,8 Hz), 7,37 (1H, d, J=2.3 Hz), 7,89 (1H, d, J=8,9 Hz), 8,69 (1H, d, J=4,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 457 (M+2H-K).

Compound 1j-3-1-1:

3-{3-(Aminosulfonyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 78

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that the compound 1h-3-1 was used instead of compound 1h-1-5.

1H-NMR (CDCl3, 270 MHz) δ (ppm): 2.49 USD (3H, s), Android 4.04 (2H, s), 6,92 (1H, d, J=3.8 Hz),? 7.04 baby mortality-to 7.09 (3H, m), 7,11-7,14 (1H, m), 7,22-7,31 (3H, m), to 7.67 (1H, d, J=8,9 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 444 (M+H).

Compound 1j-3-3-1:

3-{3-(Aminosulfonyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-6-chloro-2-oxo-2H-1-benzopyran

Chemical formula 79

Specified in the title compound was synthesized in the same conditions as described in the application is e obtain compound 1j-1-5-1, except that the compound 1h-3-3 was used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 3,95 (2H, s), at 6.84 (1H, d, J=6.9 Hz), 6,97 (1H, s), 7,02-7,05 (2H, m), 7,17 (1H, DD, J=6,9 and 6.9 Hz), 7,29 (1H, d, J=3,7 Hz), 7,34 (1H, d, J=3,7 Hz), of 7.75 (1H, s)to 8.12 (1H, s).

One of the peaks of CH3overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 478 (M+H).

Compound 1j-3-4-1:

3-{2-Fluoro-3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 80

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that the compound 1h-3-4 was used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.46 (3H, s), 3,98 (2H, s), PC 6.82-6.87 in (1H, m), 6,98? 7.04 baby mortality (1H, m), 7,10 (1H, users), 7,31-7,39 (4H, m), 7,49 (1H, d, J=2.0 Hz), 7,95 (1H, d, J=8,9 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 462 (M+H).

Compound 1j-3-4-1Na:

3-(3-Sulfanilamide-2-terbisil)-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran sodium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-3-4-1 was used instead of compound j-1-5-1.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.42 (3H, s)to 3.89 (2H, s), of 6.20 and 6.25 (1H, m), of 6.68 (1H, DD, J=7,9, 8.1 Hz), 7,19 (1H, DD, J=8,2, 8,4 Hz), 7,33-7,37 (3H, m), of 7.48 (1H, d, J=2.5 Hz), 7,92 (1H, d, J=8,9 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 462 (M+2H-Na).

Compound 1j-3-4-1K:

3-(3-Sulfanilamide-2-terbisil)-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran potassium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-3-4-1 was used instead of compound 1j-1-5-1 and KOH was used instead of NaOH.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,44 (3H, s)to 3.92 (2H, s), 6,39-of 6.45 (1H, m), 6,79 (1H, DD, J=7,1, 8.1 Hz), 7,24 (1H, DD, J=7,9, 8.1 Hz), 7,34-7,38 (3H, m), of 7.48 (1H, d, J=2.4 Hz), 7,92 (1H, d, J=8,9 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 462 (M+2H-K).

Compound 1j-3-8-1:

3-{3-(Aminosulfonyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-6-methyl-2-oxo-2H-1-benzopyran

Chemical formula 81

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that the compound 1h-3-8 was used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): and 2.26 (3H, s)to 2.46 (3H, s), 3,93 (2H, s), 6,83 (1H, d, J=7,7 Hz), 6,3-7,10 (3H, m), 7,16 (1H, DD, J=7,7, 7,7 Hz), 7,26-7,30 (2H, m), 7,44 (1H, s), a 7.85 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 458 (M+H).

Compound 1j-3-6-1:

3-{2-Chloro-3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 82

In the synthesis of compound 1j-3-4-1 specified in the title compound was isolated as a side product.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,39 (3H, s), a 4.03 (2H, s), 6,79 (1H, d, J=6.8 Hz), 7,12-7,20 (3H, m), 7,35-7,44 (4H, m), 7,52 (1H, d, J=2.5 Hz), of 7.96 (1H, d, J=9,2 Hz), 8,66 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 478 (M+H).

Compound 1j-16-1-1:

4-Methyl-3-(3-(aminosulfonyl)aminobenzyl}-7-(thiazol-5-yl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that the compound 1h-16-1 was used instead of compound 1h-1-5.

1H-NMR (Bruker (ARX-300), 300 MHz, DMSO-d6) δ (ppm): 9,17 (1H, s), 8,53 (1H, s), 7,89 (1H, d, J=8,39 Hz), 7,79 (1H, s), to 7.68 (1H, DD, J=8,39 Hz, J=1,91 Hz), 7,17 (1H, t, J=7,63 Hz), 7,03 (1H, d, J=9,54 Hz), of 6.99 (1H, s), at 6.84 (1H, d, J=7,63 Hz), 3.95 to (2H, s), 2,47 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 450,02 (M+Na).

Compound 1j-17-1-1:

4-Methyl-3-(3-(aminosulfonyl)aminobenzyl)-7-(thiazol-2-yl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that the compound 1h-17-1 was used instead of compound 1h-1-5.

1H-NMR (Bruker (ARX-300), 300 MHz, DMSO-d6) δ (ppm): 8,03 (1H, d, J=3,05 Hz), of 7.96 (2H, s), 7,92 (2H, s), 7,17 (1H, t, J=6.87 in Hz), 7,06-of 6.99 (3H, m)6,86 (1H, DD, J=8,39 Hz, J=1,91 Hz), of 3.95 (2H, s)of 2.50 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 449,88 (M+Na).

Compound 1j-20-1-1:

4-Methyl-3-(3-(aminosulfonyl)aminobenzyl)-7-(1-methyl-1H-imidazol-2-yl)-2-oxo-2H-1-benzopyran

Compound 1h-20-1 (4-methyl-3-(3-aminobenzyl)-7-(1-methyl-1H-imidazol-2-yl)-2-oxo-2H-1-benzopyran) was synthesized in the same conditions described in example obtain compound 1h-1-5, except that compound 1g-20-1 was used instead of compound 1g-1-5.

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that the compound 1h-20-1 was used instead of compound 1h-1-5.

1H-NMR (Bruker (ARX-300), 300 MHz, DMSO-d6) δ (ppm): to 7.93 (1H, d, J=8,39 Hz), of 7.75 (1H, d, J=8,39 Hz), of 7.70 (1H, s), 7,34 (1H, s), 7,17 (1H, t, J=7,63 Hz), 7,05 (1H, s), 7,03 (1H, d, J=6,10 Hz), of 6.99 (1H, s), at 6.84 (1H, d, J=7,63 Hz), of 3.97 (2H, s), of 3.85 (3H, s)of 2.50 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 424,95 (M+1).

Compound 1j-32-1-1:

4-Methyl-3-(3-(aminosulfonyl)aminobenzyl)-7-(3-methyl-3H-imida the ol-4-yl)-2-oxo-2H-1-benzopyran

Compound 1h-32-1 (4-methyl-3-(3-aminobenzyl)-7-(3-methyl-3H-imidazol-4-yl)-2-oxo-2H-1-benzopyran) was synthesized in the same conditions described in example obtain compound 1h-1-5, except that compound 1g-32-1 used instead of compound 1g-1-5.

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1, except that the compound 1h-32-1 used instead of compound 1h-1-5.

1H-NMR (Bruker (ARX-300), 300 MHz, DMSO-d6) δ (ppm): 9,34 (1H, s), 7,89 (1H, d, J=8.7 Hz), 7,78 (1H, s), 7,54 (2H, m), 7,27 (1H, s), 7,17 (1H, t, J=8.1 Hz), 7,02 (4H, m), 6,85 (1H, d, J=7.8 Hz), of 3.95 (2H, s), of 3.78 (2H, s), 2,48 (3H, s).

MS (Micromass, Quattromicro, ESI+) m/z: 425,01 (M+1).

Compound 1j-1-5-2:

6-Fluoro-4-methyl-3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 83

N-(N-methylsulfonyl)-2-oxazolidinone (27.0 mg, 0.15 mmol) was added to a solution of compound 1h-1-5 (26 mg, 0.07 mmol) in acetonitrile (4 ml) and the mixture was stirred at 80°C for 18 h Then the reaction solution was added ethyl acetate and the solution was washed with sodium carbonate solution and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate and the solvent drove under reduced davleniyeni the residue was purified column chromatography on silica gel with obtaining specified in the connection header (14,7 mg, 45%).

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,43 (3H, s), 2,53 (3H, d, J=5,1 Hz)to 2.94 (3H, s)to 3.09 (3H, s), 3,98 (2H, s), to 6.88 (1H, DD, J=6,3, 7.9 Hz), 7,01 (1H, DD, J=7,9, 7.9 Hz), 7,22 (1H, q, J=5,1 Hz), 7,27 (1H, DD, J=9,6, 8,2 Hz), of 7.48 (1H, d, J=6.8 Hz), 7,86 (1H, d, J=11,4 Hz), 9,38 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 482 (M+H).

Compound 1j-1-3-2:

3-(3-(N-methylsulfonyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 84

Sulfurylchloride (2,04 ml of 24.8 mmol) was dissolved in dichloromethane (120 ml) was added a solution of methylamine in THF (11,64 ml, with 23.3 mmol) and dimethylaminopyridine (also referred to in this document "DMAP") (2,84 g, with 23.3 mmol) at -78°C. the Mixture was stirred at room temperature for 2 h to obtain the corresponding sulfhemoglobin. To the reaction solution was added 3-(3-aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid (compound 1h-1-3) (3.0 g, 7,76 mmol), pyridine (3.2 ml) and dichloromethane (60 ml) and the mixture was stirred at room temperature overnight. Then to the reaction solution were added water and the solution was extracted with dichloromethane. After washing with sodium bicarbonate solution and saturated salt solution the organic layer was dried over anhydrous magnesium sulfate and the solvent distillate is whether under reduced pressure. The obtained residue was purified column chromatography on silica gel with obtaining specified in the title compound (540 mg).

1H-NMR (CDCl3, 270 MHz) δ (ppm): 2,44 (3H, s), 2,68 (3H, d, J=5,1 Hz), 3,05 (3H, s), 3,17 (3H, s), was 4.02 (2H, s), of 4.57 (1H, m), is 6.54 (1H, usher.), 6,90-7,00 (2H, m), to 7.09 (1H, users), 7,19-7,30 (1H, m), 7,66 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 480 (M+H).

Compound 1j-1-3-2Na:

6-Chloro-4-methyl-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid sodium salt

Chemical formula 85

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-1-3-2 was used instead of compound 1j-1-5-1.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,28 (3H, s), 2,43 (3H, s), 2,95 (3H, s), 3,11 (3H, s), 3,80 (2H, s), 4,78 (1H, usher.), of 6.29 (1H, d, J=8.1 Hz), 6,66 (1H, users), was 6.73 (1H, d, J=8.1 Hz), PC 6.82 (1H, DD, J=8,1, 8.1 Hz), 7,46 (1H, s), of 7.97 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 480 (M+2H - Na).

Compound 1j-1-3-2K:

3-(3-(N-methylsulfonyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid potassium salt

Specified in the title compound was synthesized in the same conditions that OPI is Ana in the example of a compound 1j-1-5-1Na, except that the compound 1j-1-3-2 was used instead of compound 1j-1-5-1 and KOH was used instead of NaOH.

1H NMR (CD3OD) δ (ppm): to $ 7.91 (1H, d, J=5.6 Hz), 7,32 (1H, s), 7,14-6,98 (3H, m), 6,77 (1H, d, J=7,4 Hz), was 4.02 (2H, s)3,18 (3H, s), to 3.02 (3H, s), of 2.53 (3H, s), 2,48 (3H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 480 (M+2H-K).

Compound 1j-1-1-2:

4-Methyl-3-{3-methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 86

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-2, except that the compound 1h-1-1 was used instead of compound 1h-1-3.

1H-NMR (CDCl3, 270 MHz) δ (ppm): 2,44 (3H, s)of 2.64 (3H, d, J=5,1 Hz), is 3.08 (3H, s), 3,17 (3H, s)to 4.01 (2H, s), 4,55 with 4.65 (1H, m), 6,54-7,30 (6H, m), to 7.59 (1H, d, J=5.4 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 446 (M+H).

Compound 1j-1-1S3-2:

4-Methyl-3-{3-methylaminomethyl)aminobenzyl}-2-thioxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

50 mg (0.11 mmol) of compound 1j-1-1-2 was dissolved in 1,4-dioxane and the solution was added 30 mg (0.07 mmol) of the reagent Lawson. The mixture was boiled under reflux in nitrogen atmosphere for 4 hours, the Reaction mixture was purified by HPLC Poluchenie 5 mg (10%) of compound 1j-1-1S3-2 as a yellow powder.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.42 (6H, s), 2,95 (3H, s), is 3.08 (3H, s), and 4.40 (2H, s), 6,83 (1H, d, J=7,6 Hz), of 6.96 (1H, s), 7,02 (1H, d, J=7,7 Hz), 7,16 (1H, DD, J=7,7, a 7.6 Hz), 7,22 (1H, users), 7,30 (1H, DD, J=9,0, 2,0 Hz), 7,49 (1H, d, J=2.0 Hz), of 7.96 (1H, d, J=9.0 Hz), at 9.53 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 462 (M+H).

Compound 1j-1-2-2:

6-Fluoro-4-methyl-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 87

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-1-2 was used instead of compound 1h-1-5.

1H-NMR (CD3OD, 270 MHz) δ (ppm): 2,47 (3H, s)of 2.50 (3H, s), to 3.02 (3H, s)and 3.15 (3H, s), a 4.03 (2H, s), 6,93 (1H, d, J=7.8 Hz), 7.03 is-7,13 (2H, m), 7,19 (1H, DD, J=7,8, and 7.8 Hz), 7,29 (1H, d, J=6.8 Hz), 7,66 (1H, d, J=of 11.0 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 464 (M+H).

Compound 1j-1-4-2:

3-(3-Methylmonoethanolamine-2-terbisil)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 88

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-1-4 used VM is a hundred compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,44 (3H, s), with 2.93 (3H, s), of 3.07 (3H, s), 3,98 (2H, s), 6.87 in (1H, ushort, J=7,6 Hz), 7,01 (1H, t, J=7,6 Hz), 7,15-to 7.32 (4H, m), 7,86 (1H, d, J=8.7 Hz), 9,37 (1H, users).

One of the peaks of CH3overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 464 (M+H).

Compound 1j-1-4-2Na:

3-(3-(N-methylsulfonyl)amino-2-terbisil)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid sodium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-1-4-2 was used instead of compound 1j-1-5-1.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,35 (3H, s)2:41 (3H, s), with 2.93 (3H, s), of 3.07 (3H, s), 3,88 (2H, s), of 6.20 and 6.25 (1H, m), of 6.66 (1H, DD, J=7,7, 7.9 Hz), 7,14-7,21 (2H, m), 7,24 (1H, d, J=2.3 Hz), 7,83 (1H, d, J=8.6 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 464 (M+2H-Na).

Compound 1j-1-7-2:

6-Iodine-4-methyl-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 89

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-1-7 was used instead of the who surveillance 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,43 (3H, d, J=2.7 Hz), a 2.45 (3H, s), 2,96 (3H, s), of 3.13 (3H, s), 3,93 (2H, s)6,86 (1H, d, J=8.1 Hz), 6,98-7,03 (2H, m), 7,14-of 7.23 (2H, m), 7,38 (1H, s), 8,24 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 572 (M+H).

Compound 1j-1-7-2Na:

3-(3-(N-methylsulfonyl)aminobenzyl)-6-iodine-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid sodium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-1-7-2 was used instead of compound 1j-1-5-1.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): was 2.34 (3H, s), a 2.45 (3H, s), 2,96 (3H, s), of 3.13 (3H, s), 3,86 (2H, s), of 6.52 (1H, d, J=7,7 Hz), 6,79 (1H, s), 6,85 (1H, d, J=7.8 Hz), of 6.96 (1H, DD, J=7,7, 7,8 Hz), was 7.36 (1H, s), by 8.22 (1H, C).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 572 (M+2H-Na).

Compound 1j-1-7-2K:

3-(3-(N-methylsulfonyl)aminobenzyl)-6-iodine-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid potassium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-1-7-2 was used instead of compound 1j-1-5-1 and KOH was used instead of NaOH.

1H-NMR (DMSO-d6, 27 MHz) δ (ppm): at 2.36 (3H, C)to 2.42 (3H, s), 2,96 (3H, s), 3,14 (3H, s), 3,88 (2H, s), is 6.61 (1H, d, J=7,6 Hz), at 6.84 (1H, s), 6.89 in (1H, d, J=8.1 Hz), 7,02 (1H, DD, J=7,6, 8.1 Hz), 7,37 (1H, s), by 8.22 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 572 (M+2H-K).

Compound 1j-1-8-2:

6-Methyl-4-methyl-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 90

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-1-8 was used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): of 2.23 (3H, s), 2,42 (3H, d, J=5.4 Hz), the 2.46 (3H, s)to 2.94 (3H, s), 3,10 (3H, s), 3,93 (2H, s)6,86 (1H, d, J=8.1 Hz), 7,00? 7.04 baby mortality (2H, m), 7,14-7,22 (3H, m), of 7.75 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 460 (M+H).

Compound 1j-1-8-2Na:

3-(3-(N-methylsulfonyl)aminobenzyl)-4,6-dimethyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid sodium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-1-8-2 was used instead of compound 1j-1-5-1.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,22 (3H, s), 2,32 (3H, s), is 2.44 (3H, s)to 2.94 (3H, s)to 3.09 (3H, s), a-3.84 (2H, s), 6,44 (1, d, J=7,4 Hz), to 6.75 (1H, s), for 6.81 (1H, d, J=8.1 Hz), 6,91 (1H, DD, J=7,4, 8.1 Hz), 7,20 (1H, s), 7,72 (1H, s)

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 460 (M+2H-Na).

Compound 1j-1-8-2K:

3-(3-(N-methylsulfonyl)aminobenzyl)-4,6-dimethyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid potassium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-1-8-2 was used instead of compound 1j-1-5-1 and KOH was used instead of NaOH.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,22 (3H, s), of 2.33 (3H, s), is 2.44 (3H, s)to 2.94 (3H, s)to 3.09 (3H, s), a-3.84 (2H, s), 6.48 in (1H, d, J=7.5 Hz), 6,78 (1H, s), 6,83 (1H, d, J=8,3 Hz), 6,93 (1H, DD, J=7,5, 8,3 Hz), 7,19 (1H, C)7,72 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 460 (M+2H-K).

Compound 1j-1-9-2:

6-Cyano-4-methyl-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 91

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-1-9 was used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,42 (3H, d, J=5.4 Hz), of 2.97 (3H, s), of 3.12 (3H, s), of 3.94 (2H, s), 6.87 in (1H, is, J=8.1 Hz), 7,01? 7.04 baby mortality (2H, m), 7,15-of 7.25 (2H, m), 7,60 (1H, s), 8,46 (1H, s).

One of the peaks of CH3overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 471 (M+H).

Compound 1j-1-9-2Na:

6-Cyano-4-methyl-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid sodium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-1-9-2 was used instead of compound 1j-1-5-1.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 8,42 (s, 1H), EUR 7.57 (s, 1H), PC 6.82 (t, 1H, J=7.5 Hz), 6,74 (d, 1H, J=7.9 Hz), of 6.65 (s, 1H), 6.30-in (d, 1H, J=7.4 Hz), 3,81 (s, 2H), 3,11 (s, 3H), 2,96 (s, 3H), of 2.45 (s, 3H), of 2.28 (s, 3H).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 471 (M+2H - Na).

Compound 1j-1-9-2K:

6-Cyano-4-methyl-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid potassium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-1-9-2 was used instead of compound 1j-1-5-1 and KOH was used instead of NaOH.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 8,44 (s, 1H), to 7.59 (s, 1H), 6.89 in (t, 1H, J=7.5 for the TS) is 6.78 (d, 1H, J=7.9 Hz), 6,62 (s, 1H), 6,33 (d, 1H, J=7.4 Hz), of 3.84 (s, 2H), 3,12 (s, 3H), of 2.97 (s, 3H), 2,48 (s, 3H), of 2.30 (s, 3H).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 471 (M+2H - K).

Compound 1j-1-10-2:

4-Methyl-3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 92

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-1-10 was used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,40-2,60 (6H, m), with 2.93 (3H, s), of 3.07 (3H, s), of 3.96 (2H, s), 6.75 in-6,84 (2H, m), 6,85-7,10 (1H, users), 7,18 (1H, DD, J=8,9, and 2.4 Hz), 7,27 (1H, d, J=2.4 Hz), 7,87 (1H, d, J=8.6 Hz), 8,04-8,10 (1H, m).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 447 (M+H).

Compound 1j-1-11-2:

4-Methyl-3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-6-fluoro-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinolacid

Chemical formula 93

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-1-11 was used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,40-2,60 (6H, m), 2,92 (3H;C), totaling 3.04 (3H, what), as 4.02 (2H, s), 6.75 in-PC 6.82 (2H, m), 6,82-7,05 (1H, users), of 7.48 (1H, d, J=6.2 Hz), 7,87 (1H, d, J=10,2 Hz), 8,07 (1H, m), 10,00-of 10.25 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 465 (M+H).

Compound 1j-1-11-2Na:

3-(2-(N-methylsulfonyl)aminopyridine-4-ylmethyl)-6-fluoro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid sodium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-1-11-2 was used instead of compound 1j-1-5-1.

1H NMR (CD3OD, 270 MHz) δ (ppm): 2,45 (3H, s)of 2.50 (3H, s)to 2.65 (3H, s), to 3.02 (3H, s), of 3.95 (2H, s), 6,55 (1H, DD, J=5,1 Hz, J<1.0 Hz), is 6.61 (1H, users), 7,30 (1H, d, J=6.8 Hz), to 7.67 (1H, d, J=11,1 Hz), of 7.90 (1H, d, J=5,1 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 465 (M+2H-Na).

Compound 1j-1-11-2K:

3-(2-(N-methylsulfonyl)aminopyridine-4-ylmethyl)-6-fluoro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid potassium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-1-11-2 was used instead of compound 1j-1-5-1 and KOH was used instead of NaOH.

1H NMR (CD3OD, 270 MHz) δ (ppm): 2,45 (3H, s)of 2.50 (3H, s), 265 (3H, C)to 3.02 (3H, s), of 3.95 (2H, s), 6,55 (1H, DD, J=5,1 Hz, J<1.0 Hz), is 6.61 (1H, users), 7,30 (1H, d, J=6.8 Hz), to 7.67 (1H, d, J=11,1 Hz), of 7.90 (1H, d, J=5,1 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 465 (M+2H-K).

Compound 1j-1-12-2:

4-Methyl-3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-6-chloro-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 94

2-Oxo-2H-3-(2-aminopyridine-4-ylmethyl)-4-methyl-6-chloro-1-benzopyran-7-silt ether dimethylcarbinol acid (compound 1h-1-12) was synthesized in the same conditions described in example obtain compound 1g-1-5, except that compound 5d-0-12 used instead of compound 1e-0-5.

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-1-12 was used instead of compound 1h-1-5.

1H NMR (CD3OD, 270 MHz) δ (ppm): of 2.51 (3H, s), 2.63 in (3H, s), 3.04 from (3H, s)3,18 (3H, s), of 4.13 (2H, s), 7,07 (1H, s), was 7.08 (1H, d, J=7.8 Hz), 7,35 (1H, s), of 7.97 (1H, s)to 8.12 (1H, d, J=7,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 481 (M+H).

Compound 1j-1-13-2:

4-Methyl-3-{6-(methylaminomethyl)aminopyridine-2-ylmethyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 95

1H NMR (CD3OD, 270 MHz) δ (ppm): 2,50 (3H, d, J=8.1 Hz), 3,01 (3H, s), of 3.13 (3H, s)to 4.15 (2H, s), 6,79 (1H, d, J=8.1 Hz), of 6.99 (1H, d, J=8.1 Hz), 7,10-7,20 (2H, m), 7,63 (1H, DD, J=8.1 Hz), 7,81 (1H, d, J=8.1 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 447 (M+H).

Compound 1j-1-14-2:

4-Methyl-3-{6-(methylaminomethyl)aminopyridine-2-ylmethyl}-6-fluoro-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 96

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-1-14 was used instead of compound 1h-1-5.

1H NMR (CD3OD, 270 MHz) δ (ppm): 2,25 (3H, d, J=1.9 Hz), 3,01 (3H, s)and 3.15 (3H, s)to 4.15 (2H, s), 6,79 (1H, d, J=8.1 Hz), 7,00 (1H, d, J=8.1 Hz), 7,31 (1H, d, J=6.5 Hz), a 7.62 (1H, DD, J=8.1 Hz), 7,66 (1H, d, J=11,0 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 465 (M+H).

Compound 1j-1-15-2:

4-Methyl-3-{6-(methylaminomethyl)aminopyridine-2-ylmethyl}-6-chloro-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 97

Specified in the title compound was synthesized in the same conditions, which describe the s in the example of a compound 1j-1-5-2, except that the compound 1h-1-15 was used instead of compound 1h-1-5.

1H NMR (CD3OD, 270 MHz) δ (ppm): 2,50 (3H, users), to 3.02 (3H, s), 3,17 (3H, s), 4,14 (2H, s), 6,79 (1H, d, J=7,6 Hz), of 6.99 (1H, d, J=7,6 Hz), 7,32 (1H, s), a 7.62 (1H, DD, J=7,6 Hz), 7,89 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 481 (M+H).

Compound 1j-1-4-2F:

3-(3-Methylmonoethanolamine-2-terbisil)-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 98

Acetonitrile (1.0 ml) was added to 3-(3-amino-2-terbisil)-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid (compound 1h-1-4F) (18.5 mg) and the resulting suspension was added triethylamine (0,022 ml) and methylamide 2 oxoacridine-3-sulfonic acid (19,0 mg) under stirring at room temperature. The suspension is boiled under reflux for 11 h, then the reaction mixture was added triethylamine (0,022 ml) and methylamide 2 oxoacridine-3-sulfonic acid (19,0 mg) and the mixture was further heated under reflux for 8 hours After cooling to room temperature, the reaction solution was diluted with a mixed solvent of ethyl acetate and THF (volume ratio 1:1). The organic layer was washed with 0.5 M sodium carbonate solution and saturated salt solution and ZAT is dried over anhydrous magnesium sulfate. The solvent is kept under reduced pressure and the obtained residue was purified by thin-layer chromatography on silica gel (Aminogen) (mixture diclomelan:methanol = 95:5) to obtain the specified title compound (9.8 mg).

1H NMR (CD3OD, 270 MHz) δ (ppm): is 2.74 (3H, d, J=5.4 Hz), 3.04 from (3H, s), of 3.13 (3H, s), 4,11 (2 H, s), 5,67 (2H, d, J=46,7 Hz), 6,97-7,05 (2H, m), 7,10-7,30 (2H, m), 7,37 was 7.45 (1H, m), 7,78 (1H, dt, J=7,2, 1.8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 482 (M+H).

Compound 1j-1-1-2F:

3-{3-(Methylaminomethyl)aminobenzyl}-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 99

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-4-2F, except that the compound 1h-1-1F was used instead of compound 1h-1-4F.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,42 (3H, d, J=5,1 Hz), with 2.93 (3H, s), of 3.07 (3H, s), was 4.02 (2H, users), of 5.84 (2H, d, J=46.2 Hz), at 6.84 (1H, userd, J=7,7 Hz), 7,00 (1H, users), 7,02 (1H, d, J=7,7 Hz), 7,10-7,30 (3H, m), 7,31 (1H, d, J=2.3 Hz), to $ 7.91 (1H, DD, J=8,7, and 2.3 Hz), of 9.56 (1H , users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 464 (M+H).

Compound 1j-1-2-2F:

3-{3-(Methylaminomethyl)aminobenzyl}-6-fluoro-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical forms of the La 100

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-4-2F, except that the compound 1h-1-2F was used instead of compound 1h-1-4F.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,42 (1H, d, J=5,1 Hz)to 2.94 (3H, s)to 3.09 (3H, s), a 4.03 (2H, users), of 5.83 (2H, d, J=46,3 Hz), at 6.84 (1H, d, J=7,7 Hz), 7,00 (1H, s), 7,02 (1H, userd, J=,7 Hz), 7,18 (1H, t, J=7,7 Hz), 7.23 percent (1H, q, J=5,1 Hz), 7,54 (1H, d, J=6.8 Hz), 7,89 (1H, DD, J=11,9, and 2.3 Hz), of 9.55 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 482 (M+H).

Compound 1j-1-3-2F:

6-Chloro-4-vermeil-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 101

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-4-2F, except that the compound 1h-1-3F was used instead of compound 1h-1-4F.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 9.57 (users, 1H), 8,07 (s, 1H), 7,56 (s, 1H), 7,24 (m, 1H), 7,17 (d, J=7.9 Hz, 1H),? 7.04 baby mortality (d, J=9.1 Hz, 1H), 7,00 (s, 1H), at 6.84 (d, J=7,3 Hz, 1H), 5,86 (d, J=46.2 Hz, 2H), Android 4.04 (s, 2H), 3,11 (s, 3H), 2.95 and (s, 3H), 2,42 (d, J=4,8 Hz, 3H).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 498 (M+H).

Compound 1j-1-3-2FNa:

3-{3-(Methylaminomethyl)aminobenzyl}-6-chloro-4-vermeil-2-oxo-2H-1-be supiran-7-silt ether dimethylcarbinol acid sodium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-1-3-2F was used instead of compound 1j-1-5-1.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.29 (3H, s), 2,95 (3H, s), 3,11 (3H, s), 3,90 (2H, s), of 5.84 (1H, d, J=46.2 Hz), of 6.31 (1H, userd, J=7,3 Hz), of 6.65 (1H, users), 6,76 (1H, userd, J=7,3 Hz), at 6.84 (1H, t, J=7,3 Hz), 7,53 (1H, s), 8,02 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 498 (M+2H-Na).

Compound 1j-1-3-2FK:

3-{3-(Methylaminomethyl)aminobenzyl}-6-chloro-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid potassium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-1-3-2F was used instead of compound 1j-1-5-1 and KOH was used instead of NaOH.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.29 (3H, s), 2,95 (3H, s), 3,11 (3H, s), 3,90 (2H, s), of 5.84 (1H, d, J=46.2 Hz), of 6.31 (1H, userd, J=7,3 Hz), of 6.65 (1H, users), 6,76 (1H, userd, J=7,3 Hz), at 6.84 (1H, t, J=7,3 Hz), 7,53 (1H, s), 8,02 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 498 (M+2H-K).

Compound 1j-1-3-2HE:

6-Chloro-4-(2-hydroxyethyl)-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt aired on methylcarbamyl acid

Chemical formula 102

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-4-2F, except that the compound 7d-1-3OH used instead of compound 1h-1-4F.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 8,07 (s, 1H), 7,51 (s, 1H), 7.23 percent (m, 1H), 7,16 (d, J=7.9 Hz, 1H), 7,03 (d, J=9.1 Hz, 1H), 6,98 (s, 1H), at 6.84 (d, J=7,3 Hz, 1H), 4,89 (m, 1H), 3,98 (s, 2H), 3,60 (m, 2H), 3,11 (s, 3H), 3,00 (m, 2H), 2.95 and (s, 3H), 2,42 (d, J=4,8 Hz, 3H).

ESIMC m/z: 510 (M+H).

Compound 1j-1-1-2HE:

4-(2-Hydroxyethyl)-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 103

Introduction hydroxymethylene group in the compound 1g-1-1 were carried out in the same conditions described in example obtaining compounds 7C-1-ON (connection 7C-1-ON) and the restoration of the nitro group was carried out in the same conditions described in example obtaining compounds 1h-1-5 (with connection 7d-1-ON). Then there was Sultanalieva in the same conditions described in example obtain compound 1j-1-4-2F, obtaining specified in the connection header.

1H-NMR (CDCl3, 270 MHz) δ (ppm): a 7.62 (d, J=8,4 Hz, 1H), 7,26 (s, 1H), 7,20-to 6.80 (m, 5H), 5.25-inch (d, J=5.3 Hz, 1H), 4.00 points (s, 2H), to 3.58 (m, 2H), 3,10 (s, 3H), 3,05 (m, 2H), to 3.02 (s, 3H), 2,60 (d, J=4.9 Hz, 3H), 1,79 (s, 1H).

ESMC m/z: 476 (M+H).

Compound 1j-1-3-2SD:

6-Chloro-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-4-(2-oxopropyl)-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 104

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-4-2F, except that the compound 7g-1-3CO was used instead of compound 1h-1-4F.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): of 9.56 (s, 1H), to $ 7.91 (s, 1H), 7,51 (s, 1H), 7,22 (kV, J=5,1 Hz, 1H), 7,15 (t, J=8,1 Hz, 1H), 7,02 (d, J=8.0 Hz, 1H), 6,97 (s, 1H), 6,80 (d, J=8.0 Hz, 1H), 4,30 (s, 2H), 3,91 (s, 2H), 3,10 (s, 3H), 2.95 and (s, 3H), 2,42 (d, J=4,8 Hz, 3H) 2,22 (s, 3H).

ESIMC m/z: 522 (M+H).

Compound 1j-1-3-mean:

6-Chloro-4-(2-hydroxypropyl)-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 105

Conducted the restoration of the nitro group in the 6-chloro-4-(2-hydroxypropyl)-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran-7-silt live dimethylcarbinol acid (compound 7C-1-mean) in the same conditions described in example obtain compound 1h-1-5 (with connection 7d-1-mean) and then spent Sultanalieva in the same conditions described in example obtain compound 1j-1-4-2F obtaining specified in the connection header.

1H-NMR (DMSO-d 6, 270 MHz) δ (ppm): 9,54 (s, 1 H), 8,07 (s, 1H), 7,49 (s, 1H), 7,24 (kV, J=5,1 Hz, 1H), 7,17 (t, J=8,1 Hz, 1H), 7,03 (d, J=8.0 Hz, 1H), 6,97 (s, 1H), PC 6.82 (d, J=8.0 Hz, 1H), 4,87 (d, J=5.4 Hz, 1H), was 4.02 (d, J=14,8 Hz, 1H), 3,98 (d, J=14,8 Hz, 1H), 3,85 (m, 1H), 3,10 (s, 3H), of 3.00 (m, 2H), 2.95 and (s, 3H), 2,42 (d, J=4,8 Hz, 3H) to 1.21 (d, J=5.5 Hz, 3H).

ESIMC m/z: 524 (M+H).

Compound 1j-1-3-Soome:

Methyl ester {3-(3-(methylaminomethyl)aminobenzyl)-7-dimethylcarbamoyl-2-oxo-2H-1-benzopyran-4-yl}acetic acid

Chemical formula 106

Conducted the restoration of the nitro group in the methyl ether {3-(3-nitrobenzyl)-7-dimethylcarbamoyl-2-oxo-2H-1-benzopyran-4-yl}acetic acid (compound 7f-1-coome) in the same conditions described in example obtain compound 1h-1-5 (with connection 7g-1-coome) and then spent Sultanalieva in the same conditions described in example obtain compound 1j-1-4-2F obtaining specified in the connection header.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 7,76 (d, J=8.7 Hz, 1H), 7,29 (d, J=2.5 Hz, 1H), 7.23 percent-7,13 (m, 3H), 7,03 (d, J=8,1 Hz, 1H), 6,98 (s, 1H), for 6.81 (d, J=7,6 Hz, 1H), 4,10 (s, 2H), 3,95 (s, 2H), 3,52 (s, 2H), of 3.07 (s, 3H), with 2.93 (s, 2H), 2,43 (d, J=4,8 Hz, 3H).

ESIMC m/z: 504 (M+H).

Compound 1j-1-3-2NH2:

4-Carbamoylmethyl-6-chloro-3-(3-(methylaminomethyl)aminobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the header is the compound was synthesized under the same conditions, described in the example of a connection 1j-1-5-2, except that the compound 7g-1-3CONH2was used instead of compound 1h-1-5.

1H NMR (270 MHz, DMSO-d6+CD3OD (1:4)) δ (ppm): to 8.57 (s, 1H), 8,07 (s, 1H), 7,89 (t, 1H, J=8.1 Hz), 7,76-7,73 (m, 2H), 7,65 (d, 1H, J=5.4 Hz), 4.72 in (s, 2H), 4,63 (s, 2H), 3,81 (s, 3H), 3,70 (s, 3H), 3,17 (s, 3H).

ESIMC m/z: 523 (M+H).

Compound 1j-1-3-2N2:

6-chloro-4-dimethylcarbamoyl-3-(3-(methylaminomethyl)aminobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 7g-1-3CON2was used instead of compound 1h-1-5.

1H NMR (270 MHz, CDCl3) δ (ppm): to 7.32 (s, 1H), 7,30-to 7.15 (m, 2H), 6,99 (s, 1H), 6,80 (d, 1H, J=7,2 Hz), of 6.45 (s, 1H), 6,02 (m, 1H), 3,95 (s, 2H), 3,91 (s, 2H), 3,19 (s, 3H), of 3.12 (s, 3H), of 3.07 (s, 3H), 2,98 (s, 3H), 2,56 (, 3H).

ESIMC m/z: 551 (M+H).

Compound 1j-1-37-2:

3-(3-(Methylaminomethyl)amino-6-terbisil)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-36-1, except that the compound 1j-1-1-2 was used instead of compound 1j-1-1-1.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): is 2.37 (3H, s), is 2.44 (3H, s), with 2.93 (3H, s), to 3.02 (3H, s), 3,93 (2H, s), 6.87 in (1H, m),? 7.04 baby mortality-7,22 (4H, m), 7,27 (1H, usher.), 7,88 (1H, d, J=10,8 Hz), 9,40 (1H, usher.).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 464 (M+H).

Compound 1j-1-65-2:

3-(3-(Methylaminomethyl)amino-6-terbisil)-4,6-dimethyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-36-1, except that the compound 1j-1-8-2 was used instead of compound 1j-1-1-1.

1H-NMR (CD3OD, 270 MHz) δ (ppm): 2,30 (3H, s), 2.49 USD (3H, s), 2,52 (3H, s), to 3.02 (3H, s), 3,17 (3H, s), a 4.03 (2H, s), 6,99? 7.04 baby mortality (2H, m), 7,22 (1H, m), 7,14 (1H, s), 7,71 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 478 (M+H).

Compound 1j-1-39-2:

3-(3-(Methylaminomethyl)aminobenzyl)-4-methyl-2-oxo-6-trimethylsilylethynyl-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-1-39 used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 0,24 (9H, s), 2,43 (3H, d, J=4.6 Hz), 2,47 (3H, s), 2,95 (3H, s), 3,11 (3H, s), of 3.94 (2H, s), 6,63 (1, d, J=6.9 Hz), 6,74-PC 6.82 (3H, m), 6.89 in-7,03 (2H, m), to 7.15 (1H, s), of 7.70 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 542 (M+H).

Compound 1j-1-40-2:

3-(3-(Methylaminomethyl)aminobenzyl)-6-ethinyl-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-1-40 was used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,42 (3H, d, J=4.6 Hz), the 2.46 (3H, s)to 2.94 (3H, s)to 3.09 (3H, s), 3,93 (2H, s), of 4.45 (1H, s)6,86 (1H, d, J=7,6 Hz), 6,93-7,10 (2H, m), 7,07-to 7.35 (2H, m), 7,38 (1H, s), to 7.99 (1H, s), 9,54 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 470 (M+H).

Compound 1j-1-72-2:

3-(3-(Methylaminomethyl)aminobenzyl)-4-methyl-2-oxo-2H-pyrano[2,3-b]pyridine-7-silt ether dimethylcarbinol acid

3-(3-Aminobenzyl)-4-methyl-2-oxo-2H-pyrano[2,3-b]pyridine-7-silt ether dimethylcarbinol acid (compound 1h-1-72) was synthesized in the same conditions described in example obtain compound 1h-1-5, except that compound 1g-1-72 used instead of compound 1g-1-5.

Specified in the title compound was synthesized under the same conditions described in example floor the treatment of compound 1j-1-5-2, except that the compound 1h-1-72 used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.42 (3H, s), 2,47 (3H, s), 2,95 (3H, s), 3,06 (3H, s), of 3.94 (2H, s), 6.87 in (1H, d, J=7,3 Hz), 7,01 (1H, s), 7,02 (1H, d, J=7,1 Hz), 7,14-7,20 (2H, m), 7,27 (1H, d, J=8,2 Hz), 8,43 (1H, d, J=8,2 Hz), at 9.53 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 447 (M+H).

Compound 1j-1C-1-2:

3-{3-(Methylaminomethyl)aminobenzyl}-7-(2-floratone)-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-1s-1 was used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.41 (3H, s), 3,90 (2H, s), 4,28-to 4.33 (1H, m), 4,39-of 4.44 (1H, m), 4,67-4,71 (1H, m), 4,84-4,88 (1H, m), only 6.64 (1H, d, J=7,6 Hz), 6,99-7,06 (4H, m), 7,16 (1H, DD, J=8,1, 7,8 Hz), 7,21 (1H, users), to 7.77 (1H, d, J=8.6 Hz), of 9.51 (1H, users).

One of the peaks of CH3overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 421 (M+H).

Compound 1j-1d-1-2:

3-(3-(Methylaminomethyl)aminobenzyl)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether pyrrolidin-1-carboxylic acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, drop the tion, that compound 1h-1d-1 was used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 1,84-of 1.94 (4H, m), 2,42 (3H, d, J=3.3 Hz), the 2.46 (3H, s)to 3.36 (2H, t, J=6.6 Hz), 3,52 (2H, t, J=6.6 Hz), 3,93 (2H, s)6,86 (1H, d, J=7.8 Hz), 6,98-7,05 (2H, m), 7,13-of 7.23 (3H, m), 7,26 (1H, d, J=2.3 Hz), 7,86 (1H, d, J=8,9 Hz), at 9.53 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 472 (M+H).

Compound 1j-2-4-2:

3-{2-Fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 107

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-2-4 was used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,45 (3H, s)to 3.99 (2H, s), 6,83-6,92 (1H, m), 6,97-7,06 (1H, m), 7,17 (1H, users), 7,34-7,40 (4H, m), to $ 7.91 (1H, d, J=8,4 Hz), 8,69 (2H, DD, J=4,8, 1.2 Hz), 9,38 (1H, users).

One of the peaks of CH3overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 471 (M+H).

Compound 1j-2-4-2Na:

3-{2-Fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran sodium salt

Chemical formula 108

Specified in the title compound was synthesized under the same conditions described in example receipt with the unity 1j-1-5-1Na, except that the compound 1j-2-4-2 was used instead of compound 1j-1-5-1.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,33 (3H, d, J=3.3 Hz), 2,43 (3H, s)to 3.89 (2H, s), 6,10-to 6.19 (1H, m), 6,58 of 6.66 (1H, m), 7,17 (1H, DDD, J=8,3, 1.5 Hz, JHF=8,3 HZ), 7,25 (1H, DD, J=8,7, and 2.3 Hz), 7,33 (1H, t, J=4,8 Hz), 7,37 (1H, d, J=2.3 Hz), 7,88 (1H, d, J=8.7 Hz), 8,69 (2H, d, J=4,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 471 (M+2H-Na).

Compound 1j-2-4-2K:

3-{2-Fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran potassium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-2-4-2 was used instead of compound 1j-1-5-1 and KOH was used instead of NaOH.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 8,69 (d, 2H, J=4,8 Hz), 7,88 (d, 1H, J=8.7 Hz), was 7.36 (d, 1H, J=2.3 Hz), 7,33 (t, 1H, J=4,8 Hz), 7,25 (DD, 1H, J=8,7, and 2.3 Hz), 7,16 (TD, 1H, J=8,5, and 1.4 Hz), 6,59 (t, 1H, J=7.8 Hz), 6,10 (t, 1H, J=6.3 Hz), was 4.76 (q, 1H, J=5.8 Hz), 3,88 (s, 2H), 2,43 (s, 3H), 2,32 (d, 3H, J=5.6 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 471 (M+2H-K).

Compound 1j-2-4S1-2:

3-{2-Fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-ylthio)-2-oxo-2H-1-benzopyran

Compound 1h-2-4S1 synthesized in the same conditions described in example floor the treatment of compound 1h-2-4 (synthesis scheme 2), except that compound 5d-2-4S1 was used instead of compound 4A-0-4.

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-2-4S1 was used instead of compound 1h-2-16.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,48 (3H, s)to 4.01 (2H, s), 6,83-6,92 (1H, m), 6,98-7,05 (1H, m), 7,16 (1H, users), 7,25-to 7.35 (2H, m), 7,60 (1H, d, J=8.5 Hz), 7,70-7,74 (1H, m), 7,92 (1H, d, J=8.5 Hz), 8,64 (2H, d, J=4,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 487 (M+H).

Compound 1j-2-4S2-2:

3-{2-Fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzothiophen

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-2-4S2 was used instead of compound 1h-2-16.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.54 (3H, s)4,08 (2H, s)6,70 (1H, DD, J=7,3 Hz, JHF=7,3 Hz), of 6.99 (1H, DD, J=7.9 Hz, JHF=7.9 Hz), 7,14 (1H, users), 7,28 (1H, DD, J=8,0, 8.0 Hz), 7,34 (1H, dt, J=4,9, 1.3 Hz), 7,40 (1H, DD, J=8,7, 2.2 Hz), to 7.64 (1H, d, J=2.4 Hz), 8,16 (1H, d, J=8.7 Hz), to 8.70 (2H, DD, J=4,9, 1.2 Hz), 9,44 (1H, users).

One of the peaks of CH3overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 487 (M+H).

Compound 1j-2-5-2:

3-{2-Fluoro--(methylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-6-fluoro-2-oxo-2H-1-benzopyran

Chemical formula 109

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-2-5 was used instead of compound 1h-1-5.

1H-NMR (CD3OD, 270 MHz) δ (ppm): 2,40 (3H, s), 2,68 (3H, s), 4.09 to (2H, s), 6,78? 7.04 baby mortality (3H, m), 7,17-7,39 (4H, m), 7,70-7,89 (1H, m), 8,61-8,63 (2H, m).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 489 (M+H).

Compound 1j-2-6-2:

3-{2-Methyl-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-2-6 was used instead of compound 1h-2-16.

1H NMR (Bruker 300 MHz, CDCl3) δ (ppm): 8,61 (2H, d, J=4.6 Hz), 7,72 (1H, d, J=8,4 Hz), 7,32 (1H, d, J=7,6 Hz), 7,27 (1H, d, J=3.1 Hz), 7,21 (1H, DD, J=2,3, and 8.4 Hz), 7,13 (1H, t, J=5.0 Hz), 7,07 (1H, t, J=7.8 Hz), was 6.73 (1H, d, J=a 7.6 Hz), 6,17 (1H, s), 4,36 (1H, HF), a 4.03 (2H, s), and 2.79 (3H, d, J=5.3 Hz), is 2.41 (3H, s), of 2.38 (3H, s).

MC (Micromass, Quattromicro, ESI-) m/z: 465,08 (M - H)

Compound 1j-2-4-2F:

3-{2-Fluoro-3-(methylaminomethyl)aminobenzyl}-4-vermeil-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 110

Specified in the title compound was synthesized is in the same conditions, described in the example of a connection 1j-1-5-2, except that the compound 1h-2-4F was used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 9,36 (s, 1H), 8,68 (d, J=4.9 Hz, 2H), of 7.96 (DD, J=8,9 and 2.2 Hz, 1H), 7,42 (d, J=2.4 Hz, 1H), was 7.36-7.18 in (m, 3H), 7,02 (t, J=7,0 Hz, 1H), to 6.88 (t, J=7,0 Hz, 1H), 5,86 (d, J=46.2 Hz, 2H), 4,07 (s, 2H), of 2.51 (d, J=5,1 Hz, 3H).

ESIMC m/z: 489 (M+H)

Compound 1j-2-4-2FNa:

3-{2-Fluoro-3-(methylaminomethyl)aminobenzyl}-4-vermeil-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran sodium salt

Chemical formula 111

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-2-4-2F was used instead of compound 1j-1-5-1.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 8,68 (d, J=4.9 Hz, 2H), 7,92 (DD, J=8,9, 2.7 Hz, 1H), 7,40 (d, J=2.2 Hz, 1H), 7,32 (t, J=4,7 Hz, 1H), 7,28 (DD, J=8,8, 2.3 Hz, 1H), 7,15 (t, J=8,9 Hz, 1H), return of 6.58 (t, J=7.7 Hz, 1H), 6,09 (t, J=7.8 Hz, 1H), of 5.81 (d, J=46.2 Hz, 2H), 4,71 (kV, J=5.7 Hz, 1H), 3,94 (s, 2H), 2,30 (d, J=5.7 Hz, 3H).

ESIMC m/z: 489 (M+2H-Na)

Compound 1j-2-4-2FK:

3-{2-Fluoro-3-(methylaminomethyl)aminobenzyl}-4-vermeil-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran potassium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except FR the compound 1j-2-4-2F was used instead of compound 1j-1-5-1 and KOH was used instead of NaOH.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 8,69 (d, 2H, J=4,8 Hz), 7,94 (DD, 1H, J=8,8, 2.2 Hz), 7,42 (d, 1H, J=2.3 Hz), 7,34 (t, 1H, J=4,7 Hz), 7,30 (DD, 1H, J=8,8, 2.3 Hz), 7,18 (t, 1H, J=8,9 Hz), 6,62 (t, 1H, J=7,7 Hz), 6,13 (t, 1H, J=7.8 Hz), of 5.92 (d, 2H, J=46.2 Hz), 4,80 (kV, 1H, J=5.7 Hz), of 3.96 (s, 2H), 2,33 (d, 3H, J=5.7 Hz).

Compound 1j-2-10-2:

3-{2-(Methylaminomethyl)aminopyridine-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 112

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-2-10 was used instead of compound 1h-1-5.

1H-NMR (CDCl3, 270 MHz) δ (ppm): 2,53 (3H, s), 2,82 (3H, s), 4,18 (2H, s), 7,10-to 7.35 (4H, m), 7,70-7,80 (2H, m), 8,01 (1H, d, J=6.2 Hz), 8,61 (2H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 454 (M+H).

Compound 1j-2-12-2:

3-{2-(Methylaminomethyl)aminopyridine-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-6-chloro-2-oxo-2H-1-benzopyran

Chemical formula 113

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-2-12 was used instead of compound 1h-1-5.

1H-NMR (CD3OD, 270 MHz) δ (ppm): 2,52 (3H, s)of 2.64 (3H, s), 4,11 (2H, s), 7,11 (1H, d, J=6.5 Hz), 7,13 (1H, s), 7,27 (1H, DD, J=4,9 Hz) 7,37 (1H, C)of 8.00 (1H, s)to 8.12 (1H, d, J=6.5 Hz), to 8.62 (2H, d, J=4,9 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 488 (M+H).

Compound 1j-2-16-2:

3-{2-(Methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Methylamine (158 μl, 317 mmol) and DMAP (38,7 mg, 317 mmol) was added at

-78°C to a solution of sulfurylchloride (28 μl, 340 μmol) in dichloromethane (2 ml) and the mixture is then stirred at room temperature for 2 h to obtain the corresponding sulfhemoglobin. 3-(2-Amino-3-herperidin-4-ylmethyl)-7-(pyrimidine-2-yloxy)-4-methyl-2-oxo-2H-1-benzopyran (compound 1h-2-16)(60 mg, 159 μmol), pyridine (65 μl, 795 mmol) and dichloromethane (2 ml) was added to the reaction solution and the mixture was stirred at room temperature for 4 hours After addition of water the organic layer was extracted with dichloromethane. After washing with sodium bicarbonate solution and saturated salt solution the organic layer was dried over anhydrous magnesium sulfate and the solvent is kept at reduced pressure. The obtained residue was purified column chromatography on silica gel with obtaining specified in the title compound (32 mg, 43%).

1H-NMR (CD3OD, 270 MHz) δ (ppm): to 2.54 (3H, s), 2,62 (3H, s), 4,22 (2H, s), at 6.84 (1H, DD, J=5.4 Hz), 7,20-7,30 (3H, m), 7,80-of 7.95 (2H, m), 8,63 (2H, d, J=4,9 Hz).

ESI (W IS/MS in the registration mode, the positively charged ions) m/z: 472 (M+H).

Compound 1j-2-16-2Na:

3-(2-(N-Methylsulfonyl)amino-3-herperidin-4-ylmethyl)-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran sodium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-2-16-2 was used instead of compound 1j-1-5-1.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,30 (3H, s)to 2.46 (3H, s)to 3.89 (2H, s), of 5.68 (1H, users), 6,09-6,23 (1H, m), 7,20 (1H, DD, J=2,4, and 8.7 Hz), 7,34 (1H, t, J=4,8 Hz), 7,38 (1H, d, J=2.4 Hz), 7,55 (1H, d, J=5.3 Hz), of 7.90 (1H, d, J=8.7 Hz), 8,69 (1H, d, J=4,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 472 (M+2H - Na).

Compound 1j-2-16-2K:

3-(2-(N-Methylsulfonyl)amino-3-herperidin-4-ylmethyl)-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran potassium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-2-16-2 was used instead of compound 1j-1-5-1 and KOH was used instead of NaOH.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): at 2.36 (3H, s), 2,47 (3H, s), 3,93 (2H, s), 6,26-6,40 (1H, m), 7,27 (1H, DD, J=2,3, 8.6 Hz), 7,34 (1H, t, J=4,8 Hz), 7,39 (1H, d, J=2.3 Hz), to 7.64 (1H, d, J=4,8 Hz), to $ 7.91 (1H, d, J=8.6 Hz), 8,69 (1H, d, J=4,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 472 (is+2H-K).

Compound 1j-2-16-2A:

3-{2-(Ethylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that ethylamine was used instead of methylamine.

1H-NMR (CD3OD, 270 MHz) δ (ppm): a 1.11 (3H, t, J=7.2 Hz), of 2.54 (3H, s), 3,03 (2H, q, J=7.2 Hz), of 4.12 (2H, s), at 6.84 (1H, DD, J=5.4 Hz), 7,20 7,30 (3H, m), 7,80-of 7.95 (2H, m), 8,63 (2H, d, J=4,6 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 486 (M+H).

Compound 1j-2-16-2b:

3-{2-(Isopropylaminocarbonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that Isopropylamine was used instead of methylamine.

1H-NMR (CD3OD, 270 MHz) δ (ppm): 0,85-of 1.30 (6H, m), 2,52 (3H, s), 3,45-4,20 (1H, m), 4,11 (2H, s), PC 6.82 (1H, DD, J=5.4 Hz), 7,20-7,30 (3H, m), 7,80-of 7.95 (2H, m), 8,63 (2H, d, J=4,6 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 500 (M+H).

Compound 1j-2-17-2:

3-{2-(Methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-fluoro-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-2-17 was used instead of compound 1h-2-16.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,40-2,70 (3H, m), a 4.03 (2H, s), 6.75 in-6,83 (1H, m), 6,97 (1H, users), 7,38 (1H, DD, J=4.5 Hz), 7,66 (1H, d, J=6.5 Hz), to 7.93 (1H, d, J=11,1 Hz), of 7.90-of 7.95 (1H, m), to 8.70 (2H, d, J=4,5), 10,36 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 490 (M+H).

Compound 1j-2-17-2C:

3-{2-(Cyclopropanesulfonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-fluoro-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-2-17 was used instead of compound 1h-2-16 and cyclopropylamine was used instead of methylamine.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 0,40-0,60 (4H, m), 2,24 to 2.35 (1H, m), 2.40 a-2,70 (3H, m), was 4.02 (2H, s), 6.75 in-6,85 (1H, m), 7,38 (1H, DD, J=4.5 Hz), 7,66 (1H, d, J=6.5 Hz), to 7.93 (1H, d, J=11,1 Hz), of 7.90-of 7.95 (1H, m), to 8.70 (2H,, d, J=4,5).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 516 (M+H).

Compound 1j-2-18-2:

3-{2-(Methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-chloro-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

-(2-Amino-3-herperidin-4-ylmethyl)-4-methyl-6-chloro-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran (compound 1h-2-18) was synthesized in the same conditions, described in the example of obtaining compounds 1h-2-4 (synthesis scheme 2), except that compound 5d-0-18 used instead of compound 4A-0-4.

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-2-18 used instead of compound 1h-2-16.

1H NMR (CDCl3, 270 MHz) δ (ppm): 2,47 (3H, s), was 2.76 (3H, s)4,08 (2H, s), 6,85 (1H, DD, J=5,1 Hz), 7,13 (1H, DD, J=4.9 Hz), 7,31 (1H, s), 7,73 (1H, s), to 7.93 (1H, d, J=5,1 Hz), 8,61 (2H, d, J=4,9 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 506 (M+H).

Compound 1j-2-19-2:

3-{2-(Methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-2-19 used instead of compound 1h-2-16.

1H-NMR (CD3OD, 270 MHz) δ (ppm): 2,24 (3H, s), of 2.53 (3H, s), 2,62 (3H, s), 4,11 (2H, s), for 6.81 (1H, DD, J=5,1 Hz), 7,19 (1H, s), 7,25 (1H, t, J=4,7 Hz), 7,79 (1H, s), 7,92 (1H, d, J=5,1 Hz), 8,61 (2H, d, J=4,9 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 486 (M+H).

Compound 1j-2-19-2Na:

3-(2-(N-Methylsulfonyl)amino-3-herperidin-4-ylmethyl)-4,6-dimethyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-banter the n-sodium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-2-19-2 was used instead of compound 1j-1-5-1.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): of 2.15 (3H, s), is 2.30 (3H, s), a 2.45 (3H, s)to 3.89 (2H, s), to 5.66 (1H, users), 6,07-6,21 (1H, m), 7,29-7,33 (2H, m), 7,54 (1H, d, J=5.3 Hz), 7,82 (1H, s), 8,67 (2H, DD, J=0,9, 4,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 486 (M+2H-Na).

Compound 1j-2-19-2K:

3-(2-(N-Methylsulfonyl)amino-3-herperidin-4-ylmethyl)-4,6-dimethyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran potassium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-1-19-2 was used instead of compound 1j-1-5-1 and KOH was used instead of NaOH.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): of 2.15 (3H, s), is 2.37 (3H, s), 2,47 (3H, s), 3,93 (2H, s), 6.30-in-6.42 per (1H, m), 7,29-7,33 (2H, m), to 7.67 (1H, d, J=5.3 Hz), 7,83 (1H, s), 8,67 (2H, DD, J=0,8, 4,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 486 (M+2H-K).

Compound 1j-2-19-me:

3-{2-(Methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-ethyl-6-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the header is the compound was synthesized under the same conditions, described in the example of a connection 1j-2-16-2, except that the compound 1h-2-me was used instead of compound 1h-2-16.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 1,13 (1H, t, J=7.4 Hz), 2,17 (3H, s)to 2.46 (3H, s), 2,92 (1H, userc, J=7,4 Hz), 4,00 (2H), PC 6.82 (1H, ushort, J=4,9 Hz), 7,00 (1H, userc, J=4,8 Hz), 7,32 (1H, t, J=4,8 Hz), 7,34 (1H, s), 7,86 (1H, ), to 7.93 (1H, d, J=4.9 Hz), 8,67 (2H, d, J=4,8 Hz), 10,36 (1H, s).

One of the methyl peaks overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 500 (M+H).

Compound 1j-2-19-2Na:

3-{2-(Methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-ethyl-6-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran sodium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-2-19-me was used instead of compound 1j-1-5-1.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 1,12 (1H, t, J=7,4 Hz)of 2.16 (3H, s), 2,28 (1H, d, J=5.8 Hz), 2,87 (1H, userc, J=7,4 Hz), 3,17 (3H, s), 3,85 (2H, s), of 5.50 (1H, q, J=5.8 Hz), 6,04 (1H, t, J=5,1 Hz), 7,32 (1H, s), 7,32 (1H, t, J=4,8 Hz)to 7.50 (1H, d, J=5,1 Hz), 7,82 (1H, s), 8,67 (2H, d, J=4,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 500 (M+2H-Na).

Compound 1j-2-19-Mac:

3-{2-(Methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-ethyl-6-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran Alieva salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-2-19-me was used instead of compound 1j-1-5-1 and KOH was used instead of NaOH.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 1,12 (1H, t, J=7,4 Hz)of 2.16 (3H, s), 2,28 (1H, d, J=5.8 Hz), 2,87 (1H, userc, J=7,4 Hz), 3,17 (3H, s), 3,85 (2H, s), of 5.50 (1H, q, J=5.8 Hz), 6,04 (1H, t, J=5,1 Hz), 7,32 (1H, s), 7,32 (1H, t, J=4,8 Hz)to 7.50 (1H, d, J=5,1 Hz), 7,82 (1H, s), 8,67 (2H, d, J=4,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 500 (M+2H-K).

Compound 1j-2-19-2C:

3-{2-(Cyclopropanesulfonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-2-19 used instead of compound 1h-2-16 and cyclopropylamine was used instead of methylamine.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 0,46-0,55 (4H, m)of 2.16 (3H, s), 2.26 and-is 2.37 (1H, m), a 4.03 (2H, s), 6,76-6,86 (1H, m), 7,30-7,33 (2H, m), 7,54 (1H, users), a 7.85 (1H, s), to 7.93 (1H, d, J=5.4 Hz), 8,67 (2H, d, J=4,8 Hz), 10,50 (1H, users).

One of the peaks of CH3overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 512 (M+H).

Connected the e 1j-2-16-2C:

3-{2-(Cyclopropanesulfonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that cyclopropylamine was used instead of methylamine.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 0,40-0,60 (4H, m), 2,24 to 2.35 (1H, m), 2.40 a-2,70 (3H, m), was 4.02 (2H, s), 6.75 in-6,85 (1H, m), 7,28 (1H, DD, J=1,9, and 8.4 Hz), 7,32 (1H, DD, J=4.5 Hz), 7,39 (1H, d, J=2.4 Hz), 7,52 (1H, users), to 7.93 (1H, d, J=8,4 Hz), of 7.90-of 7.95 (1H, m), 8,69 (2H, d, J=4.5 Hz), 10,49 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 498 (M+H).

Compound 1j-2-41-2:

3-{2-(Methylaminomethyl)amino-3-chloropyridin-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

2-(Di-tert-butyloxycarbonyl)amino-3-chloro-4-methylpyridine (compound 5b-0-41) was synthesized using 3-chloro-4-methyl-2-aminopyridine in the same conditions described in example obtaining compounds 5b-0-13.

2-(Di-tert-butyloxycarbonyl)amino-3-chloro-4-bromomethylphenyl (compound 5C-0-41) was synthesized using the compounds 5b-0-41 in the same conditions described in example obtaining compounds 5b-0-13.

Ethyl ester of 2-{2-(di-tert-butyloxycarbonyl)amino-3-chloropyridin-4-ylmethyl}-3-exomala the th acid (compound 5t-0-41) was synthesized using the compounds 5C-0-41 in the same conditions, described in the example of a connection 5t-0-10.

3-(3-Chloro-2-aminopyridine-4-ylmethyl)-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran (compound 5d-0-41) was synthesized using compound 5t-0-41 in the same conditions described in example obtaining compounds 5d-0-12.

3-(3-Chloro-2-aminopyridine-4-ylmethyl)-7-(pyrimidine-2-yloxy)-4-methyl-2-oxo-2H-1-benzopyran (compound 1h-2-41) was synthesized in the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that compound 5d-0-41 was used instead of compound 4A-0-4.

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-2-41 was used instead of compound 1h-2-16.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,44 (3H, s), Android 4.04 (2H, s), of 6.75 (1H, m), 7,29 (1H, DD, J=2.2, while the 8.9 Hz), 7,34 (1H, t, J=4,8 Hz), 7,41 (1H, d, J=2.2 Hz), the 7.65 (1H, userd, J=4,8 Hz), 7,94 (1H, d, J=8,9 Hz), of 8.04 (1H, m), 8,69 (2H, d, J=4,8 Hz).

One of the methyl peaks overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 488 (M+H).

Compound 1j-2-45-2:

3-{2-(Methylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtaining the soybean is inane 1j-2-16-2, except that the compound 1h-2-45 used instead of compound 1h-2-16.

1H-NMR (Bruker 300 MHz, DMSO-d6) δ (ppm): to 8.94 (1H, s), 8,69 (2H, d, J=5.0 Hz), 7,89 (1H, d, J=8,8 Hz), 7,39 (1H, d, J=2.3 Hz), 7,33 (2H, m), 7,26 (1H, DD, J=2.3 Hz, 8,8 Hz), 7.23 percent? 7.04 baby mortality (3H, m)6,91 (1H, d, J=7,6 Hz), 4.09 to (2H, s), 2,61 (3H, d, J=5.0 Hz), is 2.37 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 452,97 (M+H).

Compound 1j-2-46-2:

3-{4-(Methylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-2-46 used instead of compound 1h-2-16.

1H-NMR (Bruker 300 MHz, CDCl3) δ (ppm): 8,59 (2H, d, J=5.0 Hz), 7,69 (1H, d, J=8.7 Hz), 7.23 percent (3H, m), 7,18 (1H, DD, J=2.1 Hz, 8.7 Hz), 7,13-to 7.09 (3H, m), to 6.43 (1H, s), and 4.40 (1H, m), a 4.03 (2H, s), 2,71 (3H, d, J=5.4 Hz), 2,48 (3H, s).

MC (Micromass, Quattromicro, ESI-) m/z: 451,03 (M - H).

Compound 1j-2-52-2:

3-(3-(Methylaminomethyl)aminophenoxy)-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-2-52 was used instead of compound 1h-2-16.

1H-NMR (300 MHz, DMSO-d6) δ (ppm): 9,67 (1H, user. C)8,69 (2H, d, J=5.0 Hz), of 7.90 (1H, d, J=8,8 Hz), 7,46 (1H, q, j =2.3 Hz), 7,34 (3H, m), 7,19 (1H, m), to 6.88 (1H, m), PC 6.82 (1H, m), 6,63 (1H, DD, J=2.3 Hz, J=8,4 Hz), a 2.45 (3H, d, J=4.6 Hz), is 2.37 (3H, s).

MS(ESI+) m/z: 455,09 (M+H).

Compound 1j-2-53-2:

3-(3-(Methylaminomethyl)aminothiophenol)-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-2-53 was used instead of compound 1h-2-16.

1H-NMR (300 MHz, DMSO-d6) δ (ppm): 9,65 (1H, user. C)to 8.70 (2H, d, J=5.0 Hz), 8,00 (1H, d, J=8,8 Hz), 7,44 (1H, d, J=2.7 Hz), 7,35 (2H, m), 7,32 (1H, DD, J=2.3 Hz, J=8,8 Hz), 7,20 (1H, m), 7,00 (1H, m), of 6.96 (1H, m), 6,85 (1H, m)of 2.75 (3H, s), 2,42 (3H, d, J=4,6 Hz).

MS (ESI+) m/z: 471,03 (M+H).

Compound 1j-3-1-2:

3-{3-(Methylaminomethyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 114

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-3-1 was used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,43 (3H, d, J=3.1 Hz), of 3.94 (2H, s), 6.87 in (1H, d, J=7,3 Hz), 6,99-7,05 (2H, m), 7,13-of 7.25 (2H, m), 7,32-7,40 (3H, m), 7,49 (1H, d, J=2.5 Hz), 7,94 (1H, d, J=8,9 Hz).

One of the methyl peaks overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions)m/z: 458 (M+H).

Compound 1j-3-1-2Na:

3-(3-(N-Methylsulfonyl)aminobenzyl)-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran sodium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-3-1-2 was used instead of compound 1j-1-5-1.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,47 (3H, s), 3,91 (2H, s)of 6.71 (1H, d, J=7.5 Hz), 6,85? 7.04 baby mortality (2H, m), 7,07 (1H, t, J=7,7 Hz), 7,33-7,38 (3H, m), of 7.48 (1H, d, J=2.5 Hz), 7,92 (1H, d, J=8.7 Hz).

One of the peaks of CH3overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 458 (M+2H-Na).

Compound 1j-3-1-2K:

3-{3-(Methylaminomethyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran potassium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-3-1-2 was used instead of compound 1j-1-5-1 and KOH was used instead of NaOH.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,47 (3H, s), 3,86 (2H, s), 6,53 (1H, d, J=6.9 Hz), 6,78-6,85 (2H, m)6,94 (1H, t, J=7.8 Hz), 7,32-7,38 (3H, m), 7,47 (1H, DD, J=1,2, 2,3 Hz), 7,92 (1H, d, J=8,9 Hz).

One of the peaks of CH3overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 458 M+2N - K).

Compound 1j-3-3-2:

3-{3-(Methylaminomethyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-6-chloro-2-oxo-2H-1-benzopyran

Chemical formula 115

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-3-3 was used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,42 (3H, d, J=4.9 Hz), of 3.95 (2H, s), 6.87 in (1H, d, J=7.9 Hz), 7,01? 7.04 baby mortality (2H, m), 7,18 (1H, DD, J=7,9, 7.9 Hz), 7,25 (1H, d, J=4.9 Hz), 7,29 (1H, d, J=3.8 Hz), 7,34 (1H, d, J=3.8 Hz), 7,75 (1H, s), 8,13 (1H, s), of 9.56 (1H, s).

One of the peaks of CH3overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 492 (M+H).

Compound 1j-3-4-2:

3-{2-Fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 116

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-3-4 was used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.46 (3H, s), 3,98 (2H, s), 6,85-of 6.90 (1H, m), 6,98? 7.04 baby mortality (1H, m), 7,20 (1H, d, J=5.0 Hz), 7,29 (1H, DDD, J=1.5 and 7.8 Hz, JHP=7,8 HZ), 7,34-7,39 (3H, m), 7,49 (1H, d, J=2.5 Hz), 7,95 (1H, d, J=8,9 Hz), 9,39 (1H, users).

One of the peaks of CH3overlap the peak of DMSO.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 476 (M+H).

Compound 1j-3-4-2Na:

3-(3-(N-Methylsulfonyl)amino-2-terbisil)-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran sodium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-3-4-2 was used instead of compound 1j-1-5-1.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): is 2.37 (3H, s), 2,43 (3H, s)to 3.89 (2H, s), are 5.36 (1H, users), 6,28-6,32 (1H, m), 6,69 (1H, DD, J=7,8 and 8.1 Hz), 7,19 (1H, DD, J=7,8, 8.6 Hz), 7,31-7,40 (3H, m), 7,47 (1H, m), 7,92 (1H, d, J=8.6 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 476 (M+2H-Na).

Compound 1j-3-4-2K:

3-(3-(N-Methylsulfonyl)amino-2-terbisil}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran potassium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-3-4-2 was used instead of compound 1j-1-5-1 and KOH was used instead of NaOH.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,40 (3H, s), is 2.44 (3H, s), 3,91 (2H, s), to 5.66 (1H, users), 6,37-6.42 per (1H, m), of 6.75 (1H, DD, J=7,9, 8.0 Hz), 7,24 (1H, DD, J=8.0 a, 8,4 Hz), 7,34-7,38 (3H, m), of 7.48 (1H, DD, J=1,3, 2,3 Hz), 7,92 (1H, d, J=8,9 Hz).

ESI (LC/MS in the registration mode, the positive is on charged ions) m/z: 476 (M+2N - K).

Compound 1j-3-8-2:

3-{3-(Methylaminomethyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-6-methyl-2-oxo-2H-1-benzopyran

Chemical formula 117

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-3-8 was used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): and 2.26 (3H, s)to 2.41 (3H, d, J=4,1 Hz), the 2.46 (3H, s), 3,93 (2H, s), 6,85 (1H, d, J=7,4 Hz), 6,97? 7.04 baby mortality (2H, m), 7,13-7,24 (2H, m), 7,26-7,30 (2H, m), 7,44 (1H, s), a 7.85 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 472 (M+H).

Compound 1j-3-8-2Na:

3-(3-(N-Methylsulfonyl)aminobenzyl)-4,6-dimethyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran sodium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-3-8-2 was used instead of compound 1j-1-5-1.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): of 2.27 (3H, s), of 2.34 (3H, s)to 2.46 (3H, s), a 3.87 (2H, s), 6,53 (1H, d, J=7,1 Hz), 6,80-6,99 (4H, m), 7,27-7,31 (2H, m), 7,44 (1H, s), to 7.84 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 472 (M+2H-Na).

Compound 1j-3-8-2K:

3-(3-(N-Methylsulfonyl)aminobenzyl)-4,6-dimethyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran ka is Ieva salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-3-8-2 was used instead of compound 1j-1-5-1 and KOH was used instead of NaOH.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): of 2.27 (3H, s), of 2.34 (3H, s)to 2.46 (3H, s), a 3.87 (2H, s), 6,53 (1H, d, J=6.9 Hz), 6,79-6,99 (4H, m), 7,27-7,31 (2H, m), 7,44 (1H, s), to 7.84 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 472 (M+2H-K).

Compound 1j-3-12-2:

3-{2-(Methylaminomethyl)aminopyridine-4-ylmethyl}-4-methyl-6-chloro-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

3-(2-Aminopyridine-4-ylmethyl)-4-methyl-6-chloro-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran (compound 1h-3-12) was synthesized in the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that compound 5d-0-12 used instead of compound 4A-0-4.

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-3-12 was used instead of compound 1h-2-16.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.42 (3H, s), 2,48 (3H, s), of 3.95 (2H, s), 6,74-6,77 (2H, m), 7,25-to 7.35 (2H, m), of 7.75 (1H, s), 8,03 (1H, d, J=4.9 Hz), 8,13 (s, 1H).

ESI (LC/MS in the registration mode, the positively charged ions) m/z 493 (M+H).

Compound 1j-3-19-2:

3-{2-(Methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

3-{2-Amino-3-herperidin-4-ylmethyl}-4-methyl-6-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran (compound 1h-3-19) was synthesized in the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that compound 5d-0-18 used instead of compound 4A-0-4.

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-3-19 used instead of compound 1h-2-16.

1H NMR (CD3OD, 270 MHz) δ (ppm): was 2.34 (3H, s), of 2.51 (3H, s), 2,62 (3H, s), 4,10 (2H, s), for 6.81 (1H, DD, J=5,1 Hz), 7,13 (1H, d, J=3.8 Hz), 7,20-7,30 (2H, m), 7,80 (1H, s), 7,92 (1H, d, J=5,1 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 491 (M+H).

Compound 1j-3-19-2Na:

3-(2-(N-Methylsulfonyl)amino-3-herperidin-4-ylmethyl)-4,6-dimethyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran sodium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-3-19-2 was used instead of compound 1j-1-5-1.

1H-NMR (DMSO-d6) δ (ppm): 7,86 (1H, s)to 7.50 (1H, d, J=5,2 Hz), 7,45 (1H, s), 7,35-of 7.25 (2H, m)6,09 (1H, usher.), a 3.87 (2H, s), a 2.45 (3H, s), of 2.28 (3H, s), and 2.27 (3H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 491 (M+2H-Na).

Compound 1j-3-19-2C:

3-{2-(Cyclopropanesulfonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-3-19 used instead of compound 1h-2-16 and cyclopropylamine was used instead of methylamine.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 0,47-0,55 (4H, m), 2,23-is 2.37 (1H, m), of 2.28 (3H, s), 2.49 USD (3H, s), was 4.02 (2H, s), 6,76-6,87 (1H, m), 7,29 (2H, s), 7,47 (1H, s), 7,55 (1H, users), 7,89 (1H, s), 7,89-7,94 (1H, m), 10,48 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 517 (M+H).

Compound 1j-3-20-2:

3-{2-(Methylaminomethyl)aminopyridine-4-ylmethyl}-4-methyl-6-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

3-(2-Aminopyridine-4-ylmethyl)-7-hydroxy-6-methyl-4-methyl-2-oxo-2H-1-benzopyran (compound 5d-0-20) was synthesized using compound 5t-0-10V and 4-methylresorcinol in the same conditions described in example obtaining compounds 5d-0-12.

3-(2-Aminopyridine-4-ylmethyl)-7-(thiazol-2-ylmethyl)-6-methyl-4-methyl-2-oxo-2H-1-benzopyran (Obedinenie 1h-3-20) was synthesized in the same conditions, described in the example of obtaining compounds 1h-2-4 (synthesis scheme 2), except that compound 5d-0-20 used instead of compound 4A-0-4.

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-3-20 was used instead of compound 1h-2-16.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,28 (3H, s), a 2.45 (3H, s), 2,47 (3H, s), of 3.96 (2H, s), 6,82-6,84 (2H}m)of 6.96 (1H, usher.), 7,27-7,31 (2H, m), 7,45 (1H, s), 7,87 (1H, s), 8,07 (1H, d, J=4.3 Hz), of 10.25 (1H, usher.).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 473 (M+H).

Compound 1j-3-20-4:

{4-[4,6-Dimethyl-2-oxo-7-(thiazol-2-yloxy)-2H-1-benzopyran-3-ylmethyl]pyridine-2-yl}sulfamic acid

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,28 (3H, s)to 2.46 (3H, s), 3,90 (2H), 6,50-6,55 (1H, m), 7,13 (1H, s), 7,25-to 7.35 (2H, m), the 7.43 (1H, s), 7,80-of 8.00 (3H, m).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 460 (M+H).

Compound 1j-3-44-2:

3-{2-(Methylaminomethyl)amino-3-chloropyridin-4-ylmethyl}-4-methyl-6-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

3-(3-Chloro-2-aminopyridine-4-ylmethyl)-7-hydroxy-6-methyl-4-methyl-2-oxo-2H-1-benzopyran (compound 5d-0-44) was synthesized using compound 5t-0-41 and 4-methylresorcinol in the same conditions, described is the example for obtaining compounds 5d-0-12.

3-(3-Chloro-2-aminopyridine-4-ylmethyl)-7-(thiazol-2-yloxy)-6-methyl-4-methyl-2-oxo-2H-1-benzopyran (compound 1h-0-44) was synthesized in the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that compound 5d-0-44 was used instead of compound 4A-0-4.

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-3-44 was used instead of compound 1h-2-16.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.29 (3H, s), 2,43 (3H, s), 3,17 (3H, DD, J=1,3, 5.3 Hz), a 4.03 (2H, s), of 6.73 (1H, d, J=3.3 Hz), 9,95 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 507 (M+H).

Compound 1j-2A-4-2:

3-{2-Fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(5-ftorpirimidinu-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-2A-4 was used instead of compound 1h-2-16.

1H-NMR (Bruker 300 MHz, CDCl3) δ (ppm): 8,44 (2H, s), 7,71 (1H, d, J=8,8 Hz), 7,40 (1H, m), 7,22 (1H, d, J=2.7 Hz), 7,17 (1H, DD, J=2.3 Hz, J=9,2 Hz), 7,0 (2H, m), to 6.58 (1H, users), to 4.38 (1H, m), 4,08 (2H, s), was 2.76 (3H, d, J=5.3 Hz), 2,47 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 488,76 (M+H).

Compound 1j-2b-4-2:

3-{2-Fluoro-3-(methylamino sulfonyl)aminobenzyl}-4-methyl-7-(4-chloropyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-2b-4 was used instead of compound 1h-2-16.

1H-NMR (Bruker 300 MHz, CDCl3) δ (ppm): 8,51 (1H, d, J=5.7 Hz), 7,72 (1H, d, J=8,8 Hz), 7,41 (1H, m), 7,20 (1H, d, J=2.3 Hz), to 7.15 (1H, J=2.3 Hz, J=8,8 Hz), 7,01 (2H, m), 6,93 (1H, d, J=5.7 Hz), to 6.58 (1H, users), 4,39 (1H, m), 4.09 to (2H with), 2,77 (3H, d, J=5.3 Hz), 2,48 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 504,63 (M+H).

Compound 1j-5-4-2:

3-{2-Fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(2,4-dimethoxypyrimidine-6-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-5-4 was used instead of compound 1h-2-16.

1H-NMR (Bruker 300 MHz, CDCl3) δ (ppm): 7,66 (1H, d, J=8,8 Hz), 7,40 (1H, m), 7,16 (1H, d, J=2.3 Hz), 7,12 (1H, DD, J=2.3 Hz, J=8,8 Hz), 7,02 (1H, m), 6,97 (1H, m), is 6.61 (1H, users), 5,88 (1H, s), 4,43 (1H, m), 4,08 (2H, s), of 3.97 (3H, C)to 3.89 (3H, s), was 2.76 (3H, d, J=5.3 Hz), the 2.46 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 531,07 (M+H).

Compound 1j-3A-4-2:

3-{2-Fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(benzothiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized in the same conditions, which is s described in the example of obtaining compounds 1j-2-16-2, except that the compound 1h-3A-4 was used instead of compound 1h-2-16.

1H-NMR (Bruker 300 MHz, CDCl3) δ (ppm): 7,74 (2H, m), 7,72 (1H, d, J=8,8 Hz), 7,49 (1H, d, J=2.3 Hz), 7,38 (4H, m), 7,02 (1H, m), of 6.99 (1H, m), 6,62 (1H, user. C)of 4.44 (1H, m), 4.09 to (2H, s), was 2.76 (3H, d, J=5.3 Hz), 2,48 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 526,01 (M+H).

Compound 1j-3b-4-2:

3-{2-Fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(5-bromothiazole-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-3b-4 was used instead of compound 1h-2-16.

1H-NMR (Bruker 300 MHz, CDCl3) δ (ppm): of 7.69 (1H, d, J=8,8 Hz), 7,40 (1H, m), 7,30 (1H, d, J=2.3 Hz), 7,24 (1H, DD, J=2.3 Hz, J=8,8 Hz), 7,20 (1H, s), 7,01 (1H, m), of 6.96 (1H, m), is 6.61 (1H, users), 4,43 (1H, m), 4,07 (2H, s), was 2.76 (3H, d, J=5.3 Hz), the 2.46 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 553,79 (M), 555,78 (M+2).

Compound 1j-1A-4-2:

4-Methyl-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-1A-4 was used instead of compound 1h-2-16.

1H-NMR (Bruker 300 MHz, CDCl3) δ (ppm): 7,66 (1H, m), 7,40 (1H, m), 7,06 2H, m), 7,01 (1H, d, J=8.0 Hz), of 6.96 (1H, m), to 6.58 (1H, m), and 4.40 (1H, m), 4,07 (2H, s), 3,47 (3H, s)to 3.38 (3H, s), was 2.76 (3H, d, J=5.3 Hz), a 2.45 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 480,09 (M+H).

Compound 1j-2A-16-2:

3-{2-(Methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(5-ftorpirimidinu-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-2A-16 was used instead of compound 1h-2-16.

1H-NMR (Bruker 300 MHz, CDCl3) δ (ppm): 8,44 (2H, s), 7,71 (1H, d, J=8,8 Hz), 7,40 (1H, m), 7,22 (1H, d, J=2.7 Hz), 7,17 (1H, DD, J=2.3 Hz, J=9,2 Hz), 7,0 (2H, m), to 6.58 (1H, users), to 4.38 (1H, m), 4,08 (2H, s), was 2.76 (3H, d, J=5.3 Hz), 2,47 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 488,76 (M+H).

Compound 1j-2b-16-2:

3-{2-(Methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(4-chloropyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-2b-16 was used instead of compound 1h-2-16.

1H-NMR (Bruker 300 MHz, CDCl3) δ (ppm): charged 8.52 (1H, d, J=5.7 Hz), of 7.96 (1H, m), 7,73 (1H, d, J=8,8 Hz), 7,21 (1H, d, J=2.3 Hz), 7,17 (1H, DD, J=2.7 Hz, J=8,8 Hz), to 7.09 (1H, m)6,94 (1H, d, J=5.7 Hz), 6,90 (1H, m), vs. 5.47 (1H, m), 4.09 to (2H, s), was 2.76 (3H, d, J=5.3 Hz), 2.49 USD (3H, s).

MC (Micromass, Quattromicro, ESI+) m/: 505,87 (M), 507,86 (M+2).

Compound 1j-5-16-2:

3-{2-(Methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(2,4-dimethoxypyrimidine-6-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-5-16 used instead of compound 1h-2-16.

1H-NMR (Bruker 300 MHz, CDCl3) δ (ppm): 7,94 (1H, m), to 7.67 (1H, d, J=8,8 Hz), 7,18 (1H, d, J=2.3 Hz), 7,14 (1H, DD, J=2.3 Hz, 8,8 Hz), to 7.09 (1H, m), to 6.88 (1H, m), of 5.89 (1H, s), vs. 5.47 (1H, m), 4,08 (2H, s), 3,98 (3H, s)to 3.89 (3H, s)that was 2.76 (3H, d, J=5.3 Hz), 2,47,(3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 531,91 (M + H).

Compound 1j-3A-16-2:

3-{2-(Methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(benzothiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-3A-16 was used instead of compound 1h-2-16.

1H-NMR (Bruker 300 MHz, CDCl3) δ (ppm): 7,94 (1H, d, J=5.3 Hz), 7,73 (3H, m), 7,52 (1H, d, J=2.3 Hz), the 7.43 (1H, m), 7,39 (1H, DD, J=2.7, and an 8.8 Hz), 7,33 (1H, m), to 7.15 (1H, m), to 6.88 (1H, m), of 5.48 (1H, m), 4.09 to (2H, s), was 2.76 (3H, d, J=5.3 Hz), 2,48 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 526,73 (M + H).

Compound 1j-3b-16-2:

3-{2-(Methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(5-brontis the l-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-3b-16 was used instead of compound 1h-2-16.

1H-NMR (Bruker 300 MHz, CDCl3) δ (ppm): 7,94 (1H, m), of 7.70 (1H, d, J=8,8 Hz)}to 7.32 (1H, d, J=2.3 Hz), 7,26 (1H, d, J=2.7 Hz), 7,20 (1H, s), to 7.09 (1H, m), 6.89 in (1H, m), vs. 5.47 (1H, m), 4,07 (2H, s), was 2.76 (3H, d, J=5.3 Hz), the 2.46 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 554,62 (M), 556,54 (M+2).

Compound 1j-4-16-2:

3-{2-(Methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyrazin-2-yloxy)-2-oxo-2H-1-benzopyran

3-{2-Amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyrazin-2-yloxy)-2-oxo-2H-1-benzopyran (compound 1h-4-16) was synthesized in the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that compound 5d-0-16 was used instead of compound 4A-0-4 and bromelain used instead of 2-bromopyrimidine.

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-4-16 was used instead of compound 1h-2-16.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,44 (3H, s), 2,52 (3H, s)to 4.01 (2H, s), of 3.96 (2H, s), 6,72 (1H, d, J=5.0 Hz), 7,10-7,20 (2H, m), 7,78-a 7.85 (2H, m), of 8.09 (1H, DD, J=1,3, 2,5 Hz), of 8.27 (1H, d, J=2.5 Hz) 8,42 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 472 (M+H).

Compound 1j-6-16-2:

3-{2-(Methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyridine-2-yloxy)-2-oxo-2H-1-benzopyran

3-{2-Amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyridine-2-yloxy)-2-oxo-2H-1-benzopyran (compound 1h-6-16) was synthesized in the same conditions described in example obtain compound 1h-2-4 (synthesis scheme 2), except that compound 5d-0-16 was used instead of compound 4A-0-4 and 2-bromopyridin used instead of 2-bromopyrimidine.

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-6-16 used instead of compound 1h-2-16.

1H NMR (CD3OD, 270 MHz) δ (ppm): 2,52 (3H, s), 2,60 (3H, s), 4.09 to (2H), 6.75 in (1H, ushort, J=5.3 Hz), 7,07-7,28 (4H, m), 7,73 (1H, m), 7,83-of 7.95 (2H, m), 8,21 (1H, DD, J=1,2, 4,9 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 471 (M+H).

Compound 1j-2-47-2:

3-(3-(Methylaminomethyl)aminobenzyl)-4-hydroxy-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-2, except that the compound 1h-2-7 was used instead of compound 1h-1-3.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): of 9.51 (s, 1H), 8,68 (d, 2H, J=4,8 Hz), 8,00 (d, 1H, J=8,2 Hz), 7,33 (t, 1H, J=4,8 Hz), 7,28 (d, 1H, J=2.1 Hz), 7,19 (DD, 1H, J=8,2, 2.6 Hz), 7,13 (d, 1H, J=7,6 Hz), 7,02-7,00 (m, 2H), 6.87 in (d, 1H, J=7.4 Hz), 3,81 (s, 2H), 2,43 (d, 3H, J=4,9 Hz).

ESIMC m/z: 455 (M+H).

Compound 1j-2-51-2:

3-(3-(Methylaminomethyl)aminophenylamino)-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-2, except that the compound 1h-2-51 was used instead of compound 1h-1-3.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 9,42 (s, 1H), 8,69 (d, 2H, J=4,8 Hz), 7,83 (d, 1H, J=8.7 Hz), 7,68 (s, 1H), 7,39 (d, 1H, J=2.0 Hz), 7,33 (t, 1H, J=4,8 Hz), 7,28 (d, 1H, J=8.7 Hz), 7,14 (d, 1H, J=5,1 Hz), 7,05 (t, 1H, J=8,4 Hz), is 6.61 (d, 1H, J=8,4 Hz), 6,44 (m, 2H), 2,42 (d, 3H, J=5.4 Hz), and 2.26 (s, 3H).

ESIMC m/z: 454 (M+H).

Compound 1j-1-59-2:

3-(2-(Methylaminomethyl)aminobenzoylamino)methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-1-59 used instead of compound 1h-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 10,67 (s, 1H), 10,33 (s, 1H), 8,07 (d, 1H, J=8.1 Hz), 7,89 (d, 1H, J=8.7 Hz), 7,69 (kV, 1H, J=4.9 Hz), 7,62-6,59 (m, 2H), 7,34 (d, 1H, J=2.3 Hz), 7,267,22 (m, 2H), is 3.08 (s, 3H), 2.95 and (s, 3H), 2,48 (d, 3H, J=4.9 Hz), 2,42 (s, 3H).

ESIMC m/z: 475 (M+H).

Compound 1j-20-1-2:

4-Methyl-3-(3-(methylaminomethyl)aminobenzyl)-7-(1-methyl-1H-imidazol-2-yl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-20-1 was used instead of compound 1h-1-5.

1H-NMR (Bruker 300 MHz, CDCl3) δ (ppm): to 9.57 (1H, s), to 7.93 (1H, d, J=8,39 Hz), of 7.75 (1H, d, J=8,39 Hz), 7,71 (1H, s), 7,34 (1H, s), 7,21-7,16 (2H, m), 7,05 (3H, s), to 6.88 (1H, d, J=7,25 Hz), of 3.97 (2H, s), 3,85 (3H, s)of 2.50 (3H, s), 2,43 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 439,00 (M + 1).

Compound 1j-30-1-2:

4-Methyl-3-(3-(methylaminomethyl)aminobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether N-methyl-N-2-gidroksietilirovannogo acid

Compound 1j-0-1-2 (7-hydroxy-4-methyl-3-(3-(methylaminomethyl)aminobenzyl)-2-oxo-2H-1-benzopyran) was synthesized in the same conditions described in example obtain compound 1j-1-5-2, except that the compound 4A-0-1 was used instead of compound 1h-1-5.

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-31-1-2, except that N-methyl-N-2-hydroxyethylamine used instead of N-methyl-N-carbamoylation.

1/sup> H-NMR (Bruker (ARX-300), 300 MHz, MeOD-d4) δ (ppm): 7,83 (1H, d, J=8,77 Hz), 7,25-to 7.09 (5H, m), 7,03 (1H, d, J=7,25 Hz)4,06 (2H, s), of 3.78 (2H, t), of 3.60 (2H, t), 3,22-3,10 (3H, user. C)of 2.50 (3H, s)to 2.46 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 498,35 (M + Na).

Compound 1j-31-1-2:

4-Methyl-3-(3-(methylaminomethyl)aminobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether N-methyl-N-carbamoyltransferase acid

Compound 1j-0-1-2 (7-hydroxy-4-methyl-3-(3-(methylaminomethyl)aminobenzyl)-2-oxo-2H-1-benzopyran) was synthesized in the same conditions described in example obtain compound 1j-1-5-2, except that the compound 4A-0-1 was used instead of compound 1h-1-5.

Then to a solution of compound 1j-0-1-2 (of 33.4 mg, 0.09 mmol) in dimethylformamide (1 ml) was added triethylamine (86 μl, of 0.62 mmol) and p-NO2PhCOCl (27 μl, 0.13 mmol) at room temperature and after stirring for 30 min was added N-methyl-N-carbamoylmethyl (33 μl, 0.27 mmol) and the mixture was stirred for 10 minutes Then add the water and the organic layer was extracted twice with ethyl acetate and purified by chromatography on silica gel (mixture of methylene chloride:methanol = 20:1) to obtain the specified title compound (18 mg, 41%).

1H-NMR (Bruker (ARX-300), 300 MHz, MeOD-d4) δ (ppm): a 7.85 (1H, DD, J=8,39 Hz), 7,27-7,10 (5H, m), 6,97 (1H, d, J=7,63 Hz), 4.09 to (1H, s)4,06 (3H, s), 3,30-is 3.21 (3H, user. C)of 2.50 (3H, s)to 2.46 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/: 511,42 (M + 1).

Compound 1j-1-3-3:

6-Chloro-4-methyl-3-{3-(dimethylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 118

Compound 1h-1-3 (50 mg, 0,129 mmol) was dissolved in dichloromethane (1 ml) and pyridine (42 μl, 0,516 mmol) and to the mixture was added dimethylsulphamoyl (41 μl, 0,387 mmol). The mixture was stirred at room temperature for 24 h the Solvent in the reaction mixture is kept under reduced pressure and the obtained residue was purified column chromatography on Aminogen (dichloromethane) to obtain the specified title compound (50 mg, 79%) as a white solid.

1H-NMR (CDCl3, 270 MHz) δ (ppm): 2,45 (3H, s), was 2.76 (6H, s), 3,05 (3H, s), up 3.22 (3H, s), of 4.05 (2H, s), 6,80-of 7.60 (5H, m), 7,68 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 494 (M+H).

Compound 1j-1-3-3Na:

3-(3-(N,N-dimethylsulphamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid sodium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-1-3-3 was used instead of compound 1j-1-5-1.

1H NMR (CD3OD) δ (ppm): of 7.90 (1H, s), 7,31 (1H, s), 7.03 is-6,90 (3H,t), and 6.5 (1H, d, J=7,4 Hz)to 4.01 (2H, s)3,18 (3H, s), to 3.02 (3H, s), 2,61 (6N, C)to 2.46 (3H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 494 (M+2H - Na).

Compound 1j-1-3-3K:

3-(3-(N,N-dimethylsulphamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid potassium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-1-3-3 was used instead of compound 1j-1-5-1 and KOH was used instead of NaOH.

1H NMR (CD3OD) δ (ppm): of 7.90 (1H, s), 7,31 (1H, s), 7.03 is-of 6.90 (3H, m), of 6.65 (1H, d, J=7,4 Hz)to 4.01 (2H, s)3,18 (3H, s), to 3.02 (3H, s), 2,61 (6H, s)to 2.46 (3H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 494 (M+2H-K).

Compound 1j-2-4-3:

3-{2-Fluoro-3-(dimethylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 119

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-3, except that the compound 1h-2-4 was used instead of compound 1h-1-3.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,48 (3H, s), 2,69 (6H, s), of 4.00 (2H, s), 6,88-6,97 (1H, m), 6,97-7,06 (1H, m), 7.24 to 7,40 (4H, m), to $ 7.91 (1H, d, J=8,9 Hz), 8,69 (2H, d, J=4,8 Hz), to 9.66 (1H, users).

ESI (LC/MS in regioregularity positively charged ions) m/z: 485 (M+H).

Compound 1j-1b-1-3:

3-{3-(Dimethylaminomethyl)aminobenzyl}-7-isobutoxy-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-3, except that the compound 1h-1b-1 was used instead of compound 1h-1-3.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 0,98 (3H, s), and 1.00 (3H, s), 1,98-2,10 (1H, m), is 2.41 (3H, s), 2,61 (6H, s), 3,86 (2H, d, J=6.6 Hz), 3,90 (2H, s)6,91 (1H, d, J=7.8 Hz), 6,94? 7.04 baby mortality (4H, m), 7,18 (1H, DD, J=7,8, and 7.6 Hz), of 7.75 (1H, d, J=9.6 Hz), 9,79 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 445 (M+H).

Compound 1j-1C-1-3:

3-{3-(Dimethylaminomethyl)aminobenzyl}-7-(2-floratone)-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-3, except that the compound 1h-1s-1 was used instead of compound 1h-1-3.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,43 (3H, s), 2,61 (6H, s), 3,91 (2H, s), 4,28-to 4.33 (1H, m), 4,40-of 4.44 (1H, m), 4,67-4,71 (1H, m), 4,84-4,89 (1H, m)6,91 (1H, d, J=7,4 Hz), 6,97-7,06 (4H, m), 7,18 (1H, DD, J=8.0 a, 7,6 Hz), to 7.77 (1H, d, J=8.6 Hz), 9,79 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 435 (M+H).

Compound 1j-1C-3-3:

3-{3-(Dimethylaminomethyl)aminobenzyl}-6-chloro-7-(2-flora is hydroxy)-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-3, except that the compound 1h-1s-1 was used instead of compound 1h-1-3.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,43 (3H, s), 2,62 (6H, s), 3,91 (2H, s), to 4.38-4,43 (1H, m), 4,40-of 4.45 (1H, m), 4,70-of 4.75 (1H, m), 4,87 to 4.92 (1H, m)6,91 (1H, d, J=7.9 Hz), 7,00 (l,H, d, J=7.9 Hz), 7,03 (1H, s), 7.18 in (1H, DD, J=7,94 7.9 Hz), 7,30 (1H, s), to 7.93 (1H, s), 9,80 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 469 (M+H).

Compound 1j-1d-1-3:

3-(3-(Dimethylaminomethyl)aminobenzyl)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether pyrrolidin-1-carboxylic acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-2-3, except that the compound 1h-1d-1 was used instead of compound 1h-1-3.

1H NMR (CDCl3, 270 MHz) δ (ppm): 1,92-2,04 (4H, m), of 2.45 (3H, s), 2,80 (6H, s)a 3.50 (2H, t, J=6,7 Hz)and 3.59 (2H, t, J=6,7 Hz), a 4.03 (2H, s), 6,37 (1H, users), 6,97-was 7.08 (3H, m), 7,12-7,16 (2H, m), 7,19 (1H, d, J=7.4 Hz), to 7.61 (1H, d, J=9.4 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 486 (M+H).

Compound 1j-11-3-3:

4-Methyl-3-(3-(dimethylaminomethyl)aminobenzyl)-7-(thiophene-3-yl)-6-chloro-2-oxo-2H-1-benzopyran

Specified in the connection was synthesized in the same conditions, described in the example of a connection 1j-1-3-3, except that the compound 1h-11-3 used instead of compound 1h-1-3.

1H-NMR (Bruker 300 MHz, CDCl3) δ (ppm): of 7.70 (1H, s), 7,58 (1H, DD, J=3,05 Hz, J=1,53 Hz), 7,42 (1H, DD, J=4,96 Hz, J=0,60 Hz), 7,38 Hz (1H, s), 7,35 (1H, DD, J=4,96 Hz, J=1,53 Hz), 7,22 (1H, t, J=7,63 Hz), 7,10 (1H, s), 7,02 (2H, DD, J=8,01 Hz, J=l,91 Hz), to 6.43 (1H, s), of 4.05 (2H, s), 2,82 (6H, s), 2,47 (3H, s).

MC (Micromass, Quattromicro, ESI-) m/z: 487,25 (M - 1).

Compound 1j-12-1-3:

4-Methyl-3-(3-(dimethylaminomethyl)aminobenzyl)-7-(pyridin-4-yl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-3, except that the compound 1h-12-1 was used instead of compound 1h-1-3.

1H-NMR (Bruker (ARX-300), 300 MHz, MeOD-d4) δ (ppm): 8,72 (2H, d, J=4,58 Hz), of 7.75 (1H, d, J=8,77 Hz), to 7.59 (1H, s), 7,56 (1H, DD, J=6.87 in Hz, J=1,91 Hz), 7,53 (2H, d, J=5,72 Hz), 7,22 (1H, d, J=8,01 Hz), 7,10 (1H, s), 7,05 (1H, d, 8,39 Hz), 7,02 (1H, d, J=7,25 Hz), to 6.43 (1H, s)4,08 (2H, s), 2,82 (6H, s), 2,52 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 450,42 (M + 1).

Compound 1j-17-1-2:

4-Methyl-3-(3-(methylaminomethyl)aminobenzyl)-7-(thiazol-2-yl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-17-1 used the junction 1h-1-5.

1H-NMR (Bruker (ARX-300), 300 MHz, DMSO-d6) δ (ppm): at 9.53 (1H, s), 8,02 (1H, d, J=3,05 Hz), of 7.96 (2H, s), 7,92 (2H, d, J=3,43 Hz), 7,17 (2H, t, J=8,01 Hz), 7,02 (2H, s), 6.87 in (1H, d, J=7,63 Hz), of 3.96 (2H, s)of 2.50 (3H, s), 2,42 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 463,98 (M + Na).

Compound 1j-18-1-3:

4-Methyl-3-(3-(dimethylaminomethyl)aminobenzyl)-7-(pyridin-3-yl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-3, except that the compound 1h-18-1 was used instead of compound 1h-1-3.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 8,91 (1H, s), 8,67 (1H, s), 7,92 (1H, d, J=8,01 Hz), 7,74 (1H, d, J=8,77 Hz), 7,55 (1H, s), 7,53 (1H, DD, J=6,10 Hz, J=1,53 Hz), the 7.43 (1H, DD, J=7,25 Hz, J=0,90 Hz), 7,22 (1H, d, J=8,01 Hz), 7,11 (1H with), 7,05 (1H, d, J=8,01 Hz), 7,02 (1H, DD, J=8,77 Hz, J=1,91 Hz), 6,40 (1H, s)4,07 (2H, s), 2,82 (6H, s), 2,52 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 450,44 (M + 1).

Compound 1h-19-3-3:

4-Methyl-3-(3-(dimethylaminomethyl)aminobenzyl)-6-chloro-7-( 3-methoxyphenyl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-3, except that the compound 1h-19-3 used instead of compound 1h-1-3.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 7,71 (1H, s), 7,39 (1H, TD, J=9,16 Hz, J=1,14 Hz), 7,32 (1H, s), 7,22 (1H, t, J=8,01 Hz), 7,10 (1H, t, J=1,53 Hz), ? 7.04 baby mortality-of 6.96 (5H, m), 6,40 (1H, s)4,06 (2H, s), 3,86 (3H, s), 2,82 (6H, s), 2.49 USD (3H, s).

MC (Micromass, Quattromicro, ESI-) m/z: 511,03 (M-1).

Compound 1h-21-3-3:

4-Methyl-3-(3-(dimethylaminomethyl)aminobenzyl)-6-chloro-7-(5-acetylthiophene-2-yl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-3, except that the compound 1h-21-3 used instead of compound 1h-1-3.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): to 7.77 (2H, m), 7,44 (2H, m), 7,26 (1H, t), 7,02-to 7.00 (3H, m), 6,76 (1H, s), Android 4.04 (2H, s), of 2.81 (6H, s)at 2.59 (3H, s)to 2.46 (3H, s).

MC (Micromass, Quattromicro, ESI-) m/z: 529,15 (M - N).

Compound 1j-22-1-3:

4-Methyl-3-(3-(dimethylaminomethyl)aminobenzyl)-7-(3-acetylphenyl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-3, except that the compound 1h-22-1 was used instead of compound 1h-1-3.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): by 8.22 (1H, s), of 8.00 (1H, d, J=7,63 Hz), 7,81 (1H, d, J=8,01 Hz), 7,69 (1H, d, J=8,77 Hz), 7,62-rate of 7.54 (4H, m), 7,22 (1H, t), 7,14-7,00 (2H, m), 6.48 in (1H, user. C)of 3.95 (2H, s), of 2.81 (6H, s), 2,61 (3H, s), of 2.51 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 513,14 (M+Na).

Compound 1j-23-1-3:

4-Methyl-3-(3-(dimethylaminomethyl)aminobenzyl)-7-(4-acetylphenyl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-3, except that the compound 1h-23-1 was used instead of compound 1h-1-3.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 8,08 (2H, d, J=8,77 Hz), 7,73 (4H, d, J=8,77 Hz), 7,56 (2H, m), 7,19 (3H, m), 6.48 in (1H, user. C)to 4.15 (2H, s), of 2.81 (6H, s)to 2.65 (3H, s), of 2.51 (3H, s).

MC (Micromass, Quattromicro, ESI-) m/z: 489,07 (M - 1).

Compound 1j-1E-1-3:

4-Methyl-3-(3-(dimethylaminomethyl)aminobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether triftormetilfullerenov acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-3, except that the compound 1h-1E-1 was used instead of compound 1h-1-3.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 7,63 (2H, d, J=8,77 Hz), 7,22 (2H, m), to 7.09 (3H, m), 6,23 (1H, user. C)was 4.02 (2H, s), of 2.72 (6H, s)to 2.46 (3H, s).

MC (Micromass, Quattromicro, ESI-) m/z: 519,14 (M - 1).

Compound 1j-24-1-3:

4-Methyl-3-(3-(dimethylaminomethyl)aminobenzyl)-7-(3-cyanophenyl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-11-3, except that the compound 1j-1e-1-3 was used instead of compound 1g-1e-3 and 3-cyanoaniline acid and is used instead of thiophene-3-Bronevoy acid.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): to $ 7.91 (1H, t), of 7.82 (1H, d, J=7,63 Hz), 7,78-the 7.65 (2H, m), 7,60 (1H, t), 7,46 (2H, m), 7,20 (1H, t), 7,06 (1H, s) 7,03 (2H, t), of 6.29 (1H, user. C)to 4.15 (2H, s), of 2.81 (6H, s), of 2.51 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 474,27 (M + 1).

Compound 1j-25-1-3:

4-Methyl-3-(3-(dimethylaminomethyl)aminobenzyl)-7-(2-methoxyphenyl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-11-3, except that the compound 1j-1e-1-3 was used instead of compound 1g-1e-3 and 2-methoxyphenylalanine acid was used instead of thiophene-3-Bronevoy acid.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 7,66 (1H, d, J=8,77 Hz), 7,58 (2H, DD, J=8,77 Hz), 7,51 (2H, m), 7,25 (1H, t), 7,18 (1H, s), 7,05 (4H, m), 6,45 (1H, user. C)to 4.15 (2H, s), 3,81 (3H, s), of 2.81 (6H, s), 2.49 USD (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 479,37 (M+1).

Compound 1j-26-1-3:

4-Methyl-3-(3-(dimethylaminomethyl)aminobenzyl)-7-(4-cyanophenyl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-11-3, except that the compound 1j-1e-1-3 was used instead of compound 1g-1e-3 and 4-cyanoaniline acid was used instead of thiophene-3-Bronevoy acid.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ(ppm): 7,80-of 7.70 (5H, m), 7,72 (2H, m), 7,22 (1H, t), 7,10 (1H, s) 7,03 (2H, m), of 6.29 (1H, user. C)to 4.15 (2H, s), of 2.81 (6H, s), of 2.51 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 474,27 (M+1).

Compound 1j-27-1-3:

4-Methyl-3-(3-(dimethylaminomethyl)aminobenzyl)-7-(4-methoxyphenyl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-11-3, except that the compound 1j-1e-1-3 was used instead of compound 1g-1e-3 and 4-methoxyphenylalanine acid was used instead of thiophene-3-Bronevoy acid.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 8,08 (1H, d, J=8,01 Hz), 7,55 (1H, d, J=1,91 Hz), of 7.48 (1H, DD, J=8,39 Hz), 7,41-to 7.32 (2H, m), 7,22 (1H, t), 7,10-6,99 (5H, m), of 6.29 (1H, user. C)4,08 (2H, s), of 3.84 (3H, s), of 2.81 (6H, s), of 2.51 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 474,27 (M+1).

Compound 1j-28-1-3:

4-Methyl-3-(3-(dimethylaminomethyl)aminobenzyl)-7-(4-N,N-dimethylaminophenyl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-3, except that the compound 1h-28-1 was used instead of compound 1h-1-3.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): to 7.61 (5H, m), 7,25 (1H, t), 7,15-was 7.08 (3H, s, t), PC 6.82 (2H, d, J=8,77 Hz), to 6.39 (1H, user. C)of 4.04 (2H, s), to 3.02 (6H, s), and 2.79 (6H, s), 2,43 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 492,32 (M+1).

Compound 1j-29-1-3

4-Methyl-3-(3-(dimethylaminomethyl)aminobenzyl)-7-(benzo[1,3]dioxol-4-yl)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-11-3, except that the compound 1j-1e-1-1 was used instead of compound 1g-1e-3 and benzo[1,3]dioxol-4-Bronevoy acid was used instead of thiophene-3-Bronevoy acid.

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 7,63 (1H, d, J=8,77 Hz), 7,46 (2H, m), 7.23 percent (1H, t), 7,13 (5H, m), 6,92 (1H, d, J=8,01 Hz), 6.48 in (1H, s), of 6.02 (2H, s), Android 4.04 (2H, s), 2,80 (6H, s), 2,47 (3H, s).

MC (Micromass, Quattromicro, ESI-) m/z: 491,34 (M-1).

Compound 1j-1-21-2:

3-(3-(N-(2-Cyanoethyl)sulfamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 120

Sulfurylchloride to 66.5 μl, 872 mmol) was dissolved in dichloromethane (4 ml) and to the solution was added 2-cyanoethylene (57,2 μl, 776 mmol) and DMAP (94,7 mg, 776 mmol) at -78°C. the Mixture was stirred at room temperature to obtain the corresponding sulfhemoglobin. To the reaction solution was added 3-(3-aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid (100 mg, 258,5 mmol), pyridine (0.5 ml) and dichloromethane (2 ml) and the mixture was stirred at room temperature overnight. For the eat to the reaction solution were added water and the mixture was extracted with dichloromethane. After washing with sodium bicarbonate solution and saturated salt solution the organic layer was dried over anhydrous magnesium sulfate and the solvent is kept at reduced pressure. The obtained residue was purified column chromatography on silica gel (methanol:methylene chloride = 1:20) to obtain the specified title compound (111 mg, 83%).

1H NMR (CDCl3, 270 MHz) δ (ppm): 2,44 (3H, s), 2,44 is 2.55 (2H, m), 3.04 from (3H, s) 3,17 (3H, s), 3,15-3,30 (2H, m)to 3.99 (2H, s), 6,92-7,15 (MN, m), 7,20 (1H, s), 7,15-of 7.25 (1H, m), 7,66 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 519 (M+H).

Compound 1j-1-21-2Na:

3-(3-(N-(2-Cyanoethyl)sulfamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid sodium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-1-21-2 was used instead of compound 1j-1-5-1.

1H NMR (CD3OD) δ (ppm): 7,89 (1H, s), 7,30 (1H, s),? 7.04 baby mortality-6,98 (3H, m), 6,70 (1H, d, J=7,4 Hz)to 3.99 (2H, s), 3,17 (3H, s), to 3.02 (3H, s), 2.57 m-2,52 (2H, m), 2,48 (3H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 519 (M+2H-Na).

Compound 1j-1-21-2K:

3-(3-(N-(2-Cyanoethyl)sulfamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol KIS is the notes potassium salt

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-1Na, except that the compound 1j-1-21-2 was used instead of compound 1j-1-5-1 and KOH was used instead of NaOH.

1H NMR (CD3OD) δ (ppm): 7,89 (1H, s), 7,30 (1H, s),? 7.04 baby mortality-6,98 (3H, m), 6,70 (1H, d, J=7,4 Hz)to 3.99 (2H, s), 3,17 (3H, s), to 3.02 (3H, s), 2.57 m-2,52 (2H, m), 2,48 (3H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 519 (M+2H-K).

Compound 1j-1-22-2:

3-(3-(N-(2-Hydroxyethyl)sulfamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 121

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-21-2, except that 2-aminoethanol used instead of 2-cyanoethylene.

1H NMR (CDCl3, 270 MHz) δ (ppm): 2,44 (3H, s), 3,05 (3H, s), of 3.12 (2H, m), 3,17 (3H, s), 3,52 (2H, usher.), as 4.02 (2H, s), 6,92-7,05 (2H, m), to 7.09 (1H, users), 7,19-7,30 (1H, m), 7,66 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 510 (M+H).

Compound 1j-1-23-2:

3-(3-(N-(2-Methoxyethyl)sulfamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 122

1H NMR (CDCl3, 270 MHz) δ (ppm): 2,44 (3H, s), 3,05 (3H, s), 3,17 (3H, s), 3.15 and is 3.25 (2H, s)to 3.41 (3H, s), 3,45-3,55 (2H, m)to 4.01 (2H, s), 6,95-7,20 (2H, m), to 7.09 (1H, s), 7,19-7,30 (1H, m), 7,25 (1H, s), 7,66 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 524 (M+H).

Compound 1j-1-24-2:

3-(3-(N-(2-amino-ethyl)sulfamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid hydrochloride

Chemical formula 123

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-21-2, except that 1,2-Ethylenediamine was used instead of 2-cyanoethylene.

1H NMR (CD3OD, 270 MHz) δ (ppm): of 2.51 (3H, s), 2.95 and was 3.05 (2H, m), 3,05 (3H, s), 3,14-of 3.25 (2H, m), 3,17 (3H, s), of 4.05 (2H, s), 6,97 (1H, d, J=8.1 Hz), was 7.08 (1H, d, J=8.1 Hz), 7,12 (1H, users), 7,22 (1H, DD, J=8.1 Hz), 7,32 (1H, s), to 7.93 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 509 (M-Cl).

Compound 1j-1-25-2:

3-(3-(N-(2,3-Dihydroxypropyl)sulfamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 124

Specified in the title compound was synthesized the same conditions, described in the example of a connection 1j-1-21-2, except that 2,3-dihydroxypropyl used instead of 2-cyanoethylene.

1H NMR (CDCl3, 270 MHz) δ (ppm): of 2.38 (3H, s), 3,05 (3H, s), and 3.16 (3H, s), 3,30-3,50 (2H, m), 3,52-3,70 (1H, m)to 3.89 (2H, s)6,86 (1H, d, J=7,7 Hz), of 6.99 (1H, d, J=7,7 Hz), 7,05 (1H, s), 7,07 (1H, d, J=7,7 Hz), 7,13 (1H, s), 7,60 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 540 (M+H).

Compound 1j-1-26-2:

6-Chloro-4-methyl-3-[3-(4-methylpiperazin-1 ylsulphonyl)benzyl]-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 125

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-21-2, except that 1-methylpiperazin used instead of 2-cyanoethylene.

1H NMR (CDCl3, 270 MHz) δ (ppm): 2,22 (3H, s), 2,25-of 2.36 (4H, m), 2,43 (3H, s), 3,05 (3H, s)3,18 (3H, s), 3,20-3,30 (2H, m)to 4.01 (2H, s), 6,95-was 7.08 (2H, m), 7,15-7,30 (3H, m), the 7.65 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 549 (M+H).

Compound 1j-1-28-2:

3-(3-(N-(N'-methyl-2-amino-ethyl)methylcarbamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid hydrochloride

Chemical formula 126

Specified in the title compound was synthesized in the same in the circumstances, described in the example of a connection 1j-1-21-2, except that 2-methylaminoethanol used instead of 2-cyanoethylene.

1H NMR (CDCl3, 270 MHz) δ (ppm): to 2.41 (3H, users), of 3.00 (6H, s), 3,05 (3H, 20 users), 3,17 (3H, users), 3,50-the 3.65 (2H, m), 3,65 of 3.75 (2H, m), 3,98 (2H, users), 6,70-of 7.60 (5H, m), 7,60 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 523 (M-Cl).

Compound 1j-1-29-2:

6-Chloro-3-[3-(3,4-dihydro-1H-isoquinoline-2-ylsulphonyl)-benzyl]-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 127

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-21-2, except that isoquinoline was used instead of 2-cyanoethylene.

1H NMR (CDCl3, 270 MHz) δ (ppm): 2,30 (3H, s), is 2.74 (2H, m), 3,10 (3H, s), 3,17 (3H, s), of 3.48 (2H, m), of 3.95 (2H, s), 4,42 (2H, s), 6,92-7,27 (9H, m), 7,56 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 582 (M+H).

Compound 1j-1-30-2:

3-(3-(N-2,2,2-triftormetilfullerenov)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 128

Specified in the title compound was synthesized under the same conditions described in example obtain the program 1j-1-21-2, except that 2,2,2-triptorelin used instead of 2-cyanoethylene.

1H NMR (CDCl3, 270 MHz) δ (ppm): 2,45 (3H, s), 3.04 from (3H, s)3,18 (3H, s), 3,55-3,70 (2H, m), was 4.02 (2H, s), 7,00-7,10 (3H, m), 7,20-7,30 (1H, m), a 7.62 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 548 (M+H).

Compound 1j-1-31-2:

3-(3-(N-methoxymethanol)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 129

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-21-2, except that O-methylhydroxylamine used instead of 2-cyanoethylene.

1H NMR (CDCl3, 270 MHz) δ (ppm): 2,45 (3H, s), 3.04 from (3H, s)3,18 (3H, s), 3,76 (3H, s), was 4.02 (2H, s), is 6.78 (1H, users), 7,00-7,30 (3H, m), the 7.65 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 496 (M+H).

Compound 1j-1-32-2:

3-[3-(2-Acetylaminofluorene)benzyl]-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Compound 1h-1-3 (5.8 g, 15 mmol), 2-palmitoylethanolamide (6,1 g) and triethylamine (10.4 ml) was stirred in dichloromethane at room temperature over night. Then to the reaction mixture were added water and extraction was performed utilize the atom. The organic extract was washed with hydrochloric acid, sodium bicarbonate, water and saturated salt solution. After drying over magnesium sulfate the mixture was concentrated under reduced pressure to get crude product which was then purified column chromatography to obtain compound (9.4 g).

A portion (5.0 g) of the obtained compound and hydrazine monohydrate (0,94 ml) was stirred in a mixture of ethanol/THF at room temperature over night. Then to the reaction mixture were added water and extraction was performed with ethyl acetate. The organic extract was washed with sodium bicarbonate solution, water and saturated salt solution. After drying over magnesium sulfate the mixture was concentrated under reduced pressure to get crude product which was then purified column chromatography to obtain compound (848 mg).

Portion (50,8 mg) of the obtained compound, acetylchloride (9,5 mm) and triethylamine (28,5 ml) was stirred in methylene chloride at 0°C for 2 h Then the reaction mixture was added water, and extraction was performed with ethyl acetate. The organic extract was washed with sodium bicarbonate solution, water and saturated salt solution. After drying over magnesium sulfate the mixture was concentrated under reduced pressure to get crude product which was then purified column chromatography with floor is the increase specified in the title compound (56 mg).

1H NMR (CDCl3, 270 MHz) δ (ppm): of 1.88 (3H, in), 2.25 (3H, s), 3.04 from (3H, s), 3,10-3,30 (5H, m), 3,50-3,70 (2H, m)4,00 (2H, s), 6,95-8,00 (6H, m).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 536 (M+H).

Compound 1j-1-33-2:

6-Chloro-4-methyl-2-oxo-3-[3-(2-oxoacridine-3-sulfonylamino)benzyl]-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-21-2, except that the oxazolidinone was used instead of 2-cyanoethylene.

1H NMR (CDCl3, 270 MHz) δ (ppm): of 2.25 (3H, s), 2,95 (3H, s), 3,10 (3H, s), 3,60-of 3.80 (2H, m), 3,98 (2H, s), 4,10-4,30 (2H, m), 6,95-7,10 (3H, m), 7,25 (1H, t, J=7,7 Hz)to 7.50 (1H, s), with 8.05 (1H, s)10,80 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 536 (M+H).

Compound 1j-1d-1-2:

3-(3-(N-methylsulfonyl)aminobenzyl)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether pyrrolidin-1-carboxylic acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-2, except that the compound 1h-1d-1 was used instead of compound 1h-1-3.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 1,84-of 1.94 (4H, m), 2,42 (3H, d, J=3.3 Hz), the 2.46 (3H, s)to 3.36 (2H, t, J=6.6 Hz), 3,52 (2H, t, J=6.6 Hz), 3,93 (2H, s)6,86 (1H, d, J=7.8 Hz),6,98-7,05 (2H, m), 7,13-of 7.23 (3H, m), 7,26 (1H, d, J=2.3 Hz), 7,86 (1H, d, J=8,9 Hz), at 9.53 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 472 (M+H).

Compound 1j-1-72-2:

3-(3-(N-Methylsulfonyl)aminobenzyl)-4-methyl-2-oxo-2H-pyrano[2,3-b]pyridine-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-2, except that the compound 1h-1-72 used instead of compound 1h-1-3.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.42 (3H, s), 2,47 (3H, s), 2,95 (3H, s), 3,06 (3H, s), of 3.94 (2H, s), 6.87 in (1H, d, J=7,3 Hz), 7,01 (1H, s), 7,02 (1H, d, J=7,1 Hz), 7,14-7,20 (2H, m), 7,27 (1H, d, J=8,2 Hz), 8,43 (1H, d, J=8,2 Hz), at 9.53 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 447 (M+H).

Connection 1o-2-4-2:

2-{2-Fluoro-3-[4-methyl-2-oxo-7-(pyrimidine-2-yloxy)-2H-1-benzopyran-3-ylmethyl]phenylsulfanyl}-N-methylacetamide

Chemical formula 130

Stage 1 (obtaining a solution of compound 1l-1 in THF)

2-Propanol (130 μl, was 1.69 mmol) was added to a solution of chlorosulfonylisocyanate (1180 μl, was 1.69 mmol) in THF (3 ml) at 0°C under nitrogen atmosphere and the mixture was stirred at 0°C for 20 minutes and Then the mixture was stirred at room temperature for 2 h with quantitative getting the solution 1l-1 in THF.

Stage 2 (synthesis of compound 1m-2-4)

A solution of compound 1l-1 in THF, obtained in stage 1 (the 1.04 ml, 0,585 mmol)was added dropwise under nitrogen atmosphere to a solution of compound 1h-2-4 (214,4 mg, 0,568 mmol) and diisopropylethylamine (228 μl, 1,306 mmol) in THF (8 ml). After stirring at room temperature for 40 min, the solution was added sodium hydroxide (46,9 mg, 2,346 mmol) in water (8 ml) and methanol (0.5 ml) and the mixture was stirred for 1 h Then the reaction solution was added ethyl acetate (40 ml) and the solution is twice washed with 1 N hydrochloric acid (20 ml) and once with saturated salt solution (30 ml). The obtained organic layer was dried over sodium sulfate and the solvent is kept at reduced pressure. The obtained residue was purified by chromatography on silica gel (mixture of dichloromethane:methanol = 10:1) to obtain the compound 1m-2-4 (65.9 mg, 23%) as a pale yellow solid.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,47 (3H, 5), to 3.67 (2H, s), of 4.00 (2H, s), 6,80-to 6.88 (1H, m), 6,95? 7.04 baby mortality (1H, m), 7,22 and 7.36 (3H, m), 7,38 (1H, d, J=2.3 Hz), to $ 7.91 (1H, d, J=8,9 Hz), 8,69 (2H, d, J=4,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 500 (M+H).

Stage 3 (synthesis of compound 1o-2-4-2)

N,N-dimethylformamide (1 ml) was added to the compound 1m-2-4 (32 mg, 0,064 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (14,5 mg, 0,076 mmol) and 3-hydroxy-3,4-dihydro-4-oxo-1,2,3-be is striazolo (12,4 mg, 0,076 mmol). To the mixture was added 2.0 M solution of methylamine in THF (96 μl, 0,192 mmol) and diisopropylethylamine (22,3 μl, 0,128 mmol) and the mixture was stirred at room temperature under nitrogen atmosphere for 19 hours Then the reaction solution was added ethyl acetate (20 ml) and the solution is twice washed with 1 N hydrochloric acid, three times with saturated sodium bicarbonate solution (20 ml) and then with a saturated solution of salt. The obtained organic layer was dried over sodium sulfate and the solvent is kept at reduced pressure. The obtained residue was purified by chromatography on silica gel (mixture of methylene chloride:methanol = 10:1) and is listed in the title compound (9 mg, 28%) was obtained as a white solid.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,48 (3H, s), 2,61 (3H, d, J=4.5 Hz), of 4.00 (2H, s), 6,95-7,11 (2H, m), 7,25-7,30 (4H, m), 7,92 (1H, d, J=8,9 Hz), 8,15-8,23 (1H, m), 8,69 (2H, d, J=4,8 Hz), 9,71 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 513 (M+H).

Connection 1o-1-3-1:

3-(3-Carbamoyltransferase)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 131

Specified in the title compound was synthesized under the same conditions described in example getting connected 1o-2-4-2, except that the stage 2 compound 1h-1-3 use and instead of compound 1h-2-4 and in stage 3 the ammonia was used instead of methylamine.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,47 (3H, s), 2,95 (3H, s), 3,11 (3H, s), 3,86 (2H, s), of 3.96 (2H, s), of 6.96 (1H, d, J=5.4 Hz), 7.03 is-was 7.08 (2H, m), 7,21 (1H, m), 7,34 (1H, usher.), to 7.50 (1H, s), 7,60 (1H, usher.), 8,02 (1H, s), 9,78 (1H, usher.).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 508 (M+H).

Connection 1o-1-8-1:

3-(3-Carbamoyltransferase)-4,6-dimethyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example getting connected 1o-2-4-2, except that the compound 1h-1-8 was used instead of compound 1h-2-4 and ammonia was used instead of methylamine.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.18 (3H, s), of 2.23 (3H, s)to 2.94 (3H, s)to 3.09 (3H, s), 3,86 (2H, s), of 3.95 (2H, s), to 6.43-6,69 (1H, m), 6,76-7,31 (4H, m), 7,74 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 488 (M+H).

Connection 1o-1-3-2:

3-(3-Methylcarbamoylmethyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 132

Specified in the title compound was synthesized under the same conditions described in example getting connected 1o-2-4-2, except that the stage 2 compound 1h-1-3 was used instead of compound 1h-2-4.

1 H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,47 (3H, s), of 2.56 (3H, d, J=5.4 Hz), 2,95 (3H, s), 3,11 (3H, s), a 3.87 (2H, s), of 3.96 (2H, s), 6,98 (1H, d, J=8.1 Hz), 7.03 is-to 7.09 (2H, m), 7,22 (1H, m)to 7.50 (1H, s), 8,02 (1H, s), 8,14 (1H, d, J=5.4 Hz), 9,78 (1H, usher.).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 522 (M+H).

Connection 1o-1-8-2:

4,6-Dimethyl-3-(3-methylcarbamoylmethyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example getting connected 1o-2-4-2, except that the compound 1h-1-8 was used instead of compound 1h-2-4.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,17 (3H, s), of 2.23 (3H, s)to 2.94 (3H, s)to 3.09 (3H, s), 3,88 (2H, s), of 3.95 (2H, s), 6,97 (1H, d, J=8,4 Hz), 7,05 for 7.12 (2H, m), 7,17-7,27 (2H, m), of 7.75 (1H, s).

One of the peaks of CH3overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 502 (M+H).

Connection 1o-1-40-2:

6-Ethinyl-4-methyl-3-(3-methylcarbamoylmethyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example getting connected 1o-2-4-2, except that the compound 1h-1-40 was used instead of compound 1h-2-4.

1H is the Mr (DMSO-d 6, 270 MHz) δ (ppm): 2,17 (3H, s)to 2.94 (3H, s)to 3.09 (3H, s), 3,88 (2H, s), of 3.96 (2H, s), 4,43 (1H, s), of 6.99 (1H, d, J=6.3 Hz), 7,05-7,13 (2H, m), 7,20-7,26 (2H, m), 7,38 (1H, s), to 7.99 (1H, s), 9,77 (1H, ).

One of the peaks of CH3overlap with DMSO peak.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 512 (M+H).

Connection 1o-1-1-3:

3-(3-Dimethylallyltranstransferase)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example getting connected 1o-2-4-2, except that the compound 1h-1-1 was used instead of compound 1h-2-4 and dimethylamine was used instead of methylamine.

1H NMR (CDCl3, 270 MHz) δ (ppm): to 2.46 (3H, s)of 2.75 (3H, s)to 2.94 (6H, s), 3,06 (3H, s), of 3.94 (2H, s), 6,92 (1H, d, J=6.5 Hz), 7,00-of 7.25 (5H, m), 7,83 (1H, d, J=7,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 502 (M+H).

Connection 1o-1-3-3:

3-(3-Dimethylallyltranstransferase)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 133

Specified in the title compound was synthesized under the same conditions described in example getting connected 1o-2-4-2, except that the stage 2 compound 1h-1-3 was used instead is soedineniya 1h-2-4 and stage 3 dimethylamine was used instead of methylamine.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,47 (3H, s), was 2.76 (3H, s), 2.91 in (3H, s)to 2.94 (3H, s), 3,10 (3H, s), of 3.96 (2H, s), 4,19 (2H, s), 6,98 (1H, d, J=8.1 Hz), 7.03 is-to 7.09 (2H, m), 7.23 percent (1H, m)to 7.50 (1H, s), 8,02 (1H, s), 9,85 (1H, usher.).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 537 (M+H).

Connection 1o-3-1-1:

2-{3-[4-Methyl-2-oxo-7-(thiazol-2-yloxy)-2H-1-benzopyran-3-ylmethyl]phenylsulfanyl}ndimethylacetamide

Specified in the title compound was synthesized under the same conditions described in example getting connected 1o-2-4-2, except that the compound 1h-3-1 was used instead of compound 1h-2-4 and ammonia was used instead of methylamine.

1H NMR (CDCl3, 270 MHz) δ (ppm): to 2.46 (3H, s), 3,88 (2H, s), of 4.00 (2H, s), 6.90 to-the 7.65 (9H, m).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 486 (M+H).

Connection 1o-3-1-2:

N-Methyl-2-{3-[4-methyl-2-oxo-7-(thiazol-2-yloxy)-2H-1-benzopyran-3-ylmethyl]phenylsulfanyl}ndimethylacetamide

Specified in the title compound was synthesized under the same conditions described in example getting connected 1o-2-4-2, except that the compound 1h-3-1 was used instead of compound 1h-2-4.

1H NMR (CDCl3, 270 MHz) δ (ppm): to 2.46 (3H, s), was 2.76-2,78 (1H, m), 3,88 (2H, s), of 4.00 (2H, s), 6.90 to-the 7.65 (9H, m).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 500 (M+H)./p>

Connection 1o-3-4-2:

2-{2-Fluoro-3-[4-methyl-2-oxo-7-(thiazol-2-yloxy)-2H-1-benzopyran-3-ylmethyl]phenylsulfanyl}-N-methylacetamide

Chemical formula 134

Specified in the title compound was synthesized under the same conditions described in example getting connected 1o-2-4-2, except that the stage 2 compound 1h-3-4 was used instead of compound 1h-2-4.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.46 (3H, s), 2,60 (ZN, d, J=4.6 Hz), of 3.97 (2H, s)to 3.99 (2H, s), 6,92-7,07 (2H, m), 7,28-7,39 (4H, m)to 7.50 (1H, d, J=2.6 Hz), 7,95 (1H, d, J=8.7 Hz), 8,18 (1H, d, J=4,6 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 518 (M+H).

Connection 1o-3-1-3:

N,N-Dimethyl-2-{3-[4-methyl-2-oxo-7-(thiazol-2-yloxy)-2H-1-benzopyran-3-ylmethyl]phenylsulfanyl}ndimethylacetamide

Specified in the title compound was synthesized under the same conditions described in example getting connected 1o-2-4-2, except that the compound 1h-3-1 was used instead of compound 1h-2-4 and dimethylamine was used instead of methylamine.

1H NMR (CDCl3, 270 MHz) δ (ppm): to 2.46 (3H, s), 2,98 (3H, s), 3.04 from (3H, s), 3,88 (2H, s), of 4.00 (2H, s), 6.90 to-the 7.65 (9H, m).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 514 (M+H).

Compound 1j-1-6-4:

3-(3-Methanesulfonylaminoethyl)-4,6-dimethyl-2-oxo-2H-1-benzopyran-7-silt the ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-1-6 was used instead of compound 1h-2-16 and the acid chloride methanesulfonic acid was used instead of N-methylsulfonylamino.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,22 (3H, s), 2.49 USD (3H, s), 2,89 (6H, s), 3.04 from (3H, s), of 3.95 (2H, s), of 6.96 (1H, d, J=7,6 Hz), 7,00-was 7.08 (2H, m), 7.18 in-7,28 (2H, m), of 7.75 (1H, s), 9,63 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 445 (M+H).

Compound 1j-1-10-4:

3-(2-Methanesulfonylaminoethyl-4-ylmethyl)-4-methyl-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-2-16-2, except that the compound 1h-1-10 was used instead of compound 1h-2-16 and the acid chloride methanesulfonic acid was used instead of N-methylsulfonylamino.

1H-NMR (DMSO-d6, 300 MHz) δ (ppm): of 10.73 (users, 1H), of 8.06 (d, 1H, J=5,1 Hz), 7,87 (d, 1H, J=9.0 Hz), 7,26 (d, 1H, J=2.1 Hz), 7,19 (DD, 1H, J=8,7, 6,0 Hz), 6,85 (d, 1H, J=5.4 Hz), 6,78 (c, 1H), 3.96 points (c, 2H), 3,20 (c, 3H), 3,07 (c, 3H), 2,93 (c, 3H), 2,46 (c, 3H).

ESIMC m/z: 432 (M+H).

Compound 1j-1-3-4CONH2:

4-Carbamoylmethyl-6-chloro-3-(3-methanesulfonyl)aminobenzyl)-2-about the co-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Et3N (13 ml, 0,093 mmol) and methanesulfonamide (3.6 ml, 0,050 mmol) was added to a solution of 3-(3-aminobenzyl)-4-carbamoylmethyl-6-chloro-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid (20 mg, 0,047 mmol) in methylene chloride (1.0 ml) and the mixture was stirred at room temperature for 2 hours the Solvent drove by concentration under reduced pressure and the obtained residue was purified column chromatography to obtain specified in the title compound (5.0 mg, 22%) in the form of a white solid.

1H NMR (270 MHz, DMSO-d6+ CD3OD (1:4) δ (ppm): to 8.57 (s, 1H), 8,07 (s, 1H), of 7.90 (m, 1H), 7,82-7,74 (m, 3H), 4,74 (s, 2H), with 4.64 (s, 2H), 3,86 (s, 3H), 3,76 (s, 3H), 3,70 (s, 3H).

ESIMC m/z: 508 (M+H).

Compound 1j-1-3-4CON2:

6-Chloro-4-dimethylcarbamoyl-3-(3-methanesulfonyl)aminobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-4CONH2except that the compound 7d-1-3CONMe2 was used instead of compound 7d-1-3CON2.

1H NMR (CDCl3, 270 MHz) δ (ppm): 7,40 (s, 1H), 7.24 to 7,19 (m, 2H), 7,07-7,00 (m, 3H), of 3.97 (s, 2H), 3,80 (s, 2H), and 3.16 (s, 3H), of 3.12 (s, 3H), 3.04 from (s, 3H), 2.95 and (s, 3H), of 2.92 (s, 3H).

ESIMC m/z: 536 (M+H).

General methods -2 and -3

Yes is it provides examples of receipt, related to the common ways of -2 and -3, which was mentioned earlier.

Compound 2A-1:

2-Fluoro-1-methyl-3-nitrobenzene

Chemical formula 135

The cesium fluoride (97.5 g, 642 mmol) was added under nitrogen atmosphere to a solution of 2-chloro-1-methyl-3-nitrobenzene (73,4 g, 428 mmol) in DMSO (185 ml) and the mixture was stirred at 140°C for 10 h and Then the reaction mixture was poured into 0.5 N hydrochloric acid solution and was extracted twice with ethyl acetate. The organic extract was washed with saturated salt solution and dried over magnesium sulfate. The crude product was obtained by concentration in vacuo and then dried by distillation under reduced pressure (boiling point: 118°C-122°C/15 mm Hg) to obtain specified in the connection header (54,4 g, 82%) as a yellow oil.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): of 7.96 (m, 1H), 7,73 (m, 1H), 7,34 (t, J=8,2 Hz, 1H), 2,35 (d, J=2.4 Hz, 3H).

Rt (retention time in setting HPLC) = 2,03 minutes

The HPLC conditions:

column: Combi ODS (ODS, 5 μm, 4.6 mm inner diameter × 50 mm, Wako Pure Chemical Industries), COSMOSIL (ODS, 5 μm, 4.6 mm inner diameter × 50 mm, Nacalai Tesque), Intersil C18 (ODS, 5 μm, 4.6 mm inner diameter × 50 mm, GL Sciences) or SunFire C18 (ODS, 5 μm, 4.6 mm inner diameter × 50 mm, Waters);

mobile phase: water (A)containing 0.05% triperoxonane acid, and acetonitrile (B)containing 0.05% triperoxonane acids;

method LWIR is for: elution with a stepwise gradient of solvent (composition of the solvent was changed from 10% to 95% b over 3.5 min, then changed to 10% for 1 min and kept at 10% b for 0.5 min);

flow rate: 4.0 ml/min

Compound 1A-1:

2-methyl bromide-2-fluoro-3-nitrobenzene

Chemical formula 136

Peroxide benzoyl (10.7 g, 44 mmol) was added at boiling under reflux in a nitrogen atmosphere to a solution of 2-fluoro-1-methyl-3-nitrobenzene (compound 2A-1) (68,2 g, 440 mmol) and N-bromosuccinimide (95,0 g, 528 mmol) in carbon tetrachloride (1500 ml) and the mixture was stirred while boiling under reflux for 5 hours Then, impurities were removed by filtration and the crude product was obtained by concentration in vacuo. Then it was purified column chromatography (hexane) and specified in the header connection (68,7 g, 65%) was obtained in the form of oil color from yellow to light brown.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 8,14 (DD, J=7,0, 1,6 Hz, 1H), of 7.97 (DD, J=6,5, and 1.6 Hz, 1H), 7,46 (TD, J=8,4, and 1.4 Hz, 1H), 4,81 (d, J=1.4 Hz, 2H).

Rt if HPLC = 2,25 minutes

The HPLC conditions were the same as described in the example of obtaining compounds 2A-1.

Compound 3A-1:

Methyl ester 2-chloro-3-nitrobenzoic acid

Chemical formula 137

Concentrated sulfuric acid (2.0 ml) was added to a solution of 2-chloro-3-nitrobenzoic acid (10.0 g, of 49.6 mmol) in methanol (80 ml) and the mixture was stirred at kipac the Institute under reflux overnight. After removal of the methanol concentration in vacuo was added water, and extraction was performed with ethyl acetate. The organic extract is then washed with water, saturated sodium bicarbonate solution and saturated salt solution and dried over magnesium sulfate. Specified in the title compound (10.6 g, 99%) was obtained by concentration in vacuum in the form of a white solid.

1H NMR (CDCl3) δ (ppm): to 7.95 (DD, 1H), to 7.84 (DD, 1H), of 7.48 (t, 1H), 3,98 (s, 3H).

Rt if HPLC = 11,88 minutes

The HPLC conditions:

column: YMC-ODS-A(150×6.0 mm);

eluent: 0-20 min, MeCN/H2O = 10/90 to 100/0 (gradient)

20-30 min, MeCN/H2O = 100/0 (isocratic mode);

flow rate: 1 ml/min

Compound 2b-1:

Methyl ester 2-fluoro-3-nitrobenzoic acid

Chemical formula 138

The cesium fluoride (11.2 g) was added to a solution of methyl ester of 2-chloro-3-nitrobenzoic acid (10.6 g, is 49.0 mmol) in DMSO (49 ml) and the mixture was stirred at 140°C for 40 minutes and Then the reaction mixture was poured into water and was extracted with ethyl acetate. The organic extract is then washed with water and saturated salt solution and dried over magnesium sulfate. Then specified in the header connection (9,23 g, 95%) was obtained by concentration in vacuum in the form of a pale yellow solid.

1H NMR (CDCl3) δ (ppm):8,24-8,11 (m, 2H), 7,37 (t, 1H), 3,98 (s, 3H).

Rt if HPLC = 14,62 minutes

The HPLC conditions were the same as described in the example of obtaining compounds 3A-1.

Compound 2C-1:

(2-Fluoro-3-nitrophenyl)methanol

Chemical formula 139

DIBAL (by 115.7 ml, 1.0 M solution in toluene) was added at -78°C to a solution of methyl ester 2-fluoro-3-nitrobenzoic acid (compound 2b-1) (which 9.22 g, and 46.3 mmol) in toluene (92 ml) and the reaction mixture was stirred at -78°C for 30 min and at 0°C for 30 minutes the resulting reaction solution was again cooled to -78°C. and to the mixture was added methanol, an aqueous solution of Rochelle salt and ethyl acetate. Then the reaction mixture was stirred at room temperature for 1 h and three times were extracted with ethyl acetate. The organic layer was washed with saturated salt solution and dried over magnesium sulfate. Then specified in the header connection (7,52 g, 95%) was obtained by concentration in vacuum in the form of a brown oil.

1H NMR (CDCl3) δ (ppm): to 7.95 (m, 1H), to 7.84 (t, 1H), 7,31 (m, 1H), to 4.87 (s, 2H).

Rt if HPLC = 7,52 minutes

The HPLC conditions were the same as described in the example of obtaining compounds 3A-1.

Compound 2C-2:

4-Fluoro-3-nitrobenzyloxy alcohol

Sodium borohydride (1,36 g, 35,95 mmol) was added to a solution of 4-fluoro-3-nitrobenzaldehyde (2.0 g, 11,83 mmol) in methane is Le (15 ml) and water (3.0 ml) and the mixture was stirred at room temperature for 3 hours Then to the reaction mixture were added water and extraction was performed with ethyl acetate. The organic extract was washed with saturated salt solution and dried over magnesium sulfate and then concentrated under reduced pressure to obtain specified in the title compound (2.10 g, 95%) as a pale red oil.

1H NMR (CDCl3, 270 MHz) δ (ppm): of 8.06 (DD, 1H, J=7,1, 2.2 Hz), to 7.64 (m, 1H), 7,28 (DD, 1H, J=10,7, 8.6 Hz), was 4.76 (s, 2H).

Compound 1A-1:

1-methyl bromide-2-fluoro-3-nitrobenzene

Chemical formula 140

The solution tribromide phosphorus (4.8 ml) in anhydrous diethyl ether (100 ml) was added at 0°C. to a solution of (2-fluoro-3-nitrophenyl)methanol (compound 2C-1) (7,52 g, and 46.3 mmol) in anhydrous diethyl ether (130 ml) and the mixture was stirred for 30 min at 0°C. Then the reaction mixture was poured into ice water and was extracted with ethyl acetate. The organic extract was sequentially washed with saturated sodium bicarbonate solution, water and saturated salt solution and dried over magnesium sulfate. Then got mentioned in the title compound (7,10 g, 70%) as a brown oil.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 8,14 (DD, J=7,0, 1,6 Hz, 1H), of 7.97 (DD, J=6,5, and 1.6 Hz, 1H), 7,46 (TD, J=8,4, and 1.4 Hz, 1H), 4,81 (d, J=1.4 Hz, 2H).

Rt if HPLC = 2,25 minutes

The HPLC conditions were the same as described in the example of a connection 2 is-1.

Compound 1A-2:

2-methyl bromide-4-fluoro-3-nitrobenzene

Tribromide phosphorus (1.13 ml) was added to a solution of 4-fluoro-3-nitrobenzyl alcohol (2.1 g, 11,23 mmol) in diethyl ether (40 ml) and the mixture was stirred at room temperature for 1 h Then the reaction mixture was added water, and extraction was performed with ethyl acetate. The organic extract was washed with a saturated solution of sodium bicarbonate and a saturated solution of salt. After drying over magnesium sulfate and concentration under reduced pressure, the obtained residue was purified column chromatography to obtain specified in the connection header (2,50 mg, 95%) as a pale yellow solid.

1H NMR (CDCl3, 270 MHz) δ (ppm): 8,10 (DD, 1H, J=7,1, 2.2 Hz), to 7.67 (m, 1H), 7,29 (DD, 1H, J=10,7, 8.6 Hz), of 4.49 (s, 2H).

Compound 2C-73:

(5-Nitrothiophen-2-yl)methanol

NaBH4(248 mg, 6,55 mmol) was slowly added to a solution of (5-nitrothiophen-2-yl)aldehyde (1,03 g, 6,55 mmol) in methanol (10 ml) under cooling on ice. The mixture was heated to room temperature and the mixture was stirred for 4 h and Then to the mixture was added 1 N aqueous HCl (20 ml) and twice held the extraction with ethyl acetate (40 ml). Then the organic layer was purified by chromatography on silica gel (hexane:ethyl acetate = 3:1) to obtain the decree of the frame and the title compound (917 mg, 88%).

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): of 7.82 (1H, d, J=3,82 Hz), 6,93 (1H, d, J=4,20 Hz), 4,88 (2H, s), of 2.21 (1H, s).

Compound 1A-73:

(5-Nitrothiophen-2-yl)methyl ester methanesulfonic acid

Methylene chloride (8.5 ml), triethylamine (0,90 ml, 6.42 per mmol) and acid chloride methanesulfonic acid (0,43 ml, 5,61 mmol) was mixed with compound 2C-73 (851 mg, to 5.35 mmol) at 0°C. the Mixture was stirred at 0°C for 1 h and to the mixture was added water (10 ml). The organic layer was extracted with methylene chloride (10 ml) and the solvent drove with obtaining specified in the title compound (1.25 g, 98.5 per cent).

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): to 7.84 (1H, d, J=4,20 Hz), 7,13 (1H, d, J=4,20 Hz), are 5.36 (2H, s), 3,06 (3H, s).

General method 4

The following are examples of the preparation associated with the General method 4, which was mentioned earlier.

Compound 4A-0-4:

2-Oxo-2H-3-(2-fluoro-3-aminobenzyl)-4-methyl-7-hydroxy-1-benzopyran

Chemical formula 141

The tin chloride (II) dihydrate (561 mg, 2.49 mmol) was added under nitrogen atmosphere to a solution of starting compound 1E-0-4 (150 mg, 0.46 mmol) in ethyl acetate (4 ml) and boiled under reflux for 1 h Then the reaction solution was added saturated sodium bicarbonate solution and the mixture was extracted with ethyl acetate. The organic layer is washed is whether saturated salt solution and dried over anhydrous sodium sulfate and the solvent is kept at reduced pressure. The obtained residue was purified column chromatography on silica gel (mixture of dichloromethane:methanol = 30:1 to 10:1) to obtain specified in the connection header (91,8 mg, 88%) as a white solid.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,35 (3H, s), 3,85 (2H, s), is 5.06 (2H, users), of 6.20 (1H, DDD, J=7,6, 1.5 Hz, JHF=7,6 Hz), 6,59 (1H, DDD, J=8,24 1.5 Hz, JHF=8,2 Hz), 6,67 to 6.75 (2H, m), for 6.81 (1H, DD, J=8,7, 2.4 Hz), to 7.64 (1H, d, J=2.4 Hz), of 10.47 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 300 (M+H).

Compound 4A-0-5:

2-Oxo-2H-3-(2-fluoro-3-aminobenzyl)-4-methyl-6-fluoro-7-hydroxy-1-benzopyran

Chemical formula 142

Specified in the title compound was synthesized under the same conditions described in example obtain compound 4A-0-4, except that the compound 1E-0-5 was used instead of compound 1E-0-4.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,32 (3H, s), a-3.84 (2H, s), of 6.20 (1H, DD, J=7,1, 7,1 Hz), 6,58-6,87 (3H, m), 7,55 (1H, d, J=11.0 in Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 318 (M+H).

Compound 4A-0-1:

2-Oxo-2H-3-(3-aminobenzyl)-4-methyl-7-hydroxy-1-benzopyran

Chemical formula 143

Specified in the title compound was synthesized under the same conditions described in example obtain compound 4A-0-4, except FR the compound 1E-0-1 was used instead of compound 1E-0-4.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): at 2.36 (3H, s), 3,32 (2H, ushers in), 3.75 (2H, s), 4,96 (1H, users), 6,32-to 6.43 (3H, m), of 6.71 (1H, d, J=2.4 Hz), for 6.81 (1H, DD, J=2,4 8,7 Hz), 6.89 in (1H, DDD, J=2,1, to 7.3, and 7.3 Hz), to 7.64 (1H, d, J=8.7 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 282 (M+H).

Compound 4A-0-3:

2-Oxo-2H-3-(3-aminobenzyl)-4-methyl-6-chloro-7-hydroxy-1-benzopyran

Chemical formula 144

Specified in the title compound was synthesized under the same conditions described in example obtain compound 4A-0-4, except that the compound 1E-0-3 was used instead of compound 1E-0-4.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): at 2.36 (3H, s), 3,32 (2H, users), with 3.79 (2H, s), is 4.93 (1H, users), 6,29-to 6.43 (3H, m), 6,82-6,93 (2H, m), 7,79 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 316 (M+H).

Compound 4A-0-6:

3-(2-Methyl-3-aminobenzyl)-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 4A-0-4, except that the compound 1E-0-6 was used instead of compound 1E-0-4.

1H-NMR (Bruker 300 MHz, DMSO-d6) δ (ppm): 10,49 (1H, s), 7,63 (1H, d, J=8,8 Hz), PC 6.82 (1H, DD, J=2,3, 8,8 Hz), 6,72 of 6.68 (2H, m), 6.48 in (1H, d, J=7,6 Hz), of 5.99 (1H, d, J=7,6 Hz), of 4.77 (2H, s), with 3.79 (2H, in), 2.25 (3H, s)2,07 (3H, s).

MC (Micromass, Quattromicro, SI+) m/z: 295,95 (M+H).

Compound 4A-0-45:

3-(2-Aminobenzyl)-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

10% Pd/C (15 mg, 20 wt./wt.%) was added to a solution of compound 1E-0-45 (75 mg, 2.4 mmol) in methanol (1 ml) and the mixture was stirred for 1 h in an atmosphere of molecular hydrogen under a pressure of 1 ATM. Pd/C was removed by filtration and the filtrate was purified by chromatography on silica gel (mixture of methylene chloride:methanol = 10:1) to obtain the specified title compound (25 mg, 37%).

1H-NMR (Bruker 300 MHz, DMSO-d6) δ (ppm): 10,44 (1H, s), to 7.64 (1H, d, J=8,8 Hz), to 6.88 (1H, t, J=7.4 Hz), PC 6.82 (1H, DD, J=2.3 Hz, 8,8 Hz), was 6.73 (1H, d, J=1.9 Hz), of 6.65 (1H, d, J=8.0 Hz), to 6.58 (1H, d, J=7,6 Hz), 6,41 (1H, t, a 7.6 Hz), 5,00 (2H, s), the 3.65 (2H, s), a 2.36 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 281,84 (M+H).

Compound 4A-0-46:

3-(4-Aminobenzyl)-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 4A-0-4, except that the compound 1E-0-46 was used instead of compound 1E-0-4.

1H-NMR (Bruker 300 MHz, DMSO-d6) δ (ppm): 10,44 (1H, s), to 7.61 (1H, d, J=8,8 Hz), 6,85 (2H, d, J=8,4 Hz), 6,79 (1H, DD, J=2.3 Hz, 8,8 Hz), of 6.68 (1H, d, J=2.3 Hz), 6,45 (2H, d, J=8,4 Hz), 4,84 (2H, s), and 3.72 (2H, s), is 2.37 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 281,65 (M+H).

Compound 4A-0-51:

3-(3-Aminophenylamino)-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 4A-0-4, except that the compound 4A-0-51 was used instead of compound 1E-0-4.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 10,37 (s, 1H), to 7.59 (d, 1H, J=8,9 Hz), 7,02 (s, 1H), 6,84 (DD, 1H, J=8,6, and 2.3 Hz), 6,80-of 6.73 (m, 3H), 5,98-5,88 (m, 2H), 5,80 (m, 1H), of 5.05 (users, 1H), 2,22 (s, 3H).

ESIMC m/z: 283 (M+H).

Compound 4A-0-73:

3-(5-Nitrothiophen-2-ylmethyl)-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

A mixture of compound 1E-0-73 (30 mg, 0,095 mmol) with acetic acid (0.15 ml) was combined with a mixture of tin chloride (II) dihydrate (129 mg, or 0.57 mmol) and concentrated hydrochloric acid (0.25 ml) at room temperature and the resulting mixture was stirred for 2 hours was Added water (10 ml) and the mixture was stirred for 10 min and then was added a saturated solution of NaHCO3to bring the pH of the reaction mixture to 10. The organic layer was extracted twice with a mixture of methylene chloride and methanol (5:1) (20 ml). Then it was purified by chromatography on silica gel (hexane:ethyl acetate = 1:3) to obtain the specified title compound (5 mg, 18%).

1H-NMR (Bruker 300 MHz, DMSO-d6) δ (ppm): 10,36 (1H, s), 7,63 (1H, d, J=8,77 Hz), 6,97 (1H, DD, J=8,77, 2.30 GHz), 6,69 (1H, d, J=2.30 Hz), 6,30 (1H, d, J=3,43 Hz), 5,63 (1H, d, J=3,43 Hz)to 5.17 (2H, s), 3,82 (2H, s), is 2.40 (3H, s).

MC (Micromass, Quattromicro, ESI+) m/z: 288,03 (M + 1).

Compound 1h-2-4:

4-Methyl-3-(2-fluoro-3-aminobenzyl)-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 145

Scheme of synthesis of 2

60% suspension of sodium hydride (11.5 mg, 0.28 mmol) was added under nitrogen atmosphere to a solution of starting compound 4A-0-4 (90,6 mg, 0.30 mmol) in N,N-dimethylformamide (2 ml) and the mixture was stirred at room temperature for 1 h Then to the mixture was added 2-bromopyrimidine (48 mg, 0.30 mmol) and the mixture was stirred at 100°C for 5 hours Then the reaction solution was added ethyl acetate and the solution washed with sodium bicarbonate solution, water and saturated salt solution. The organic layer was dried over anhydrous sodium sulfate and the solvent is kept at reduced pressure. The obtained residue was purified column chromatography on silica gel (mixture of dichloromethane:methanol = 1:0 to 40:1) to obtain specified in the connection header (of 60.5 mg, 56%) as a white solid.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,45 (3H, s), 3,93 (2H, s)5,08 (2H, users), and 6.25 (1H, DDD, J=7,2, 1.7 Hz, JHF=7,2 Hz), is 6.61 (1H, DDD, J=8,2) and 1.7 Hz, JHF=8,2 Hz), 6.73 x (1 H, DD, J=8,2, 7,2 Hz), 7,26 (1H, DD, J=8,8, 2.4 Hz), 7,34 (1H, t, J=4,8 Hz), 7,37 (1H, d, J=2.4 Hz), 7,89 (1H, d, J=8,8 Hz), 8,68 (2H, d, J=4,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 378 (M+H).

Compound 1h-3-4:

4-Methyl-3-(2-fluoro-3-am is mobinil)-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 146

Scheme of synthesis of 2

The original compound 4A-0-4 (5.0 g, 16.9% mmol) was dissolved in N,N-dimethylformamide (75 ml) and to the mixture was added 2-bromothiazole (6,0 ml of 67.6 mmol) and cesium carbonate (11,0 g, 33.8 mmol). The mixture was stirred at 100°C for 19 h Then the reaction solution was added ethyl acetate and the solution washed with water and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate and the solvent is kept at reduced pressure. The obtained residue was purified column chromatography on silica gel (mixture of dichloromethane:methanol = 50:1) to obtain the specified title compound (2.4 g, 38%) as a pale yellow powder.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,44 (3H, s)to 3.92 (2H, s), 6,24 (1H, DDD, J=1,5, 7,0 Hz, JHF=7,0 Hz), is 6.61 (1H, DDD, J=1,5, 8,3 Hz, JHF=8,3 Hz), 6,72 (1H, DD, J=7,0, 8,3 Hz), 7,34-7,38 (4H, m), 7,49 (1H, d, J=2.5 Hz), 7,92 (1H, d, J=8,9 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 383 (M+H).

A common way-5

The following are examples of the preparation related to General method 5, which was mentioned earlier.

Compound 5b-0-13:

2-(Di-tert-butyloxycarbonyl)amino-6-methylpyridin

Chemical formula 147

2-Amino-6-methylpyridin (15 g, 138, 7mm mmol) and Vos2On (41,4 ml, 180,3 mmol) was stirred at 60 the With during the night and to the mixture was added 100 ml of THF at room temperature. The reaction solution was slowly added dropwise to the mixed solution Vos2On (95,6 ml, 416,1 mmol) and DMAP (59.3 g, 485,5 mmol) and the mixture was stirred at room temperature for 4 h Then the reaction solution was added ethyl acetate and the solution was washed with a solution of ammonium chloride, sodium bicarbonate solution and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate and the solvent is kept at reduced pressure. The obtained residue was purified column chromatography on silica gel with obtaining specified in the connection header (34.8 g, 82%) as a white solid.

1H NMR (CDCl3, 270 MHz) δ (ppm): 1,31-of 1.39 (18H, m), 2,42 (3H, s), 7,14 (1H, d, J=7,6 Hz), 7,17 (1H, d, J=7,6 Hz), 7,74 (1H, DD, J=7,6 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 309 (M+H).

Compound 5C-0-13:

2-(Di-tert-butyloxycarbonyl)amino-6-(methyl bromide)pyridine

Chemical formula 148

In nitrogen atmosphere 6-(di-tert-butoxycarbonyl)amino-2-methylpyridine (compound 5b-0-13) (6.0 g, a 19.5 mmol), N-bromosuccinimide (4.5 g, to 25.3 mmol) and benzoyl peroxide (675 mg, of 1.95 mmol) was stirred at 80°C for 4 h and Then the reaction solution was filtered and the solvent is kept at reduced pressure. The obtained residue was purified column chromatography on silica gel with receiving the receiving specified in the connection header (4,34 g).

1H NMR (CDCl3, 270 MHz) δ (ppm): 1,31-of 1.39 (18H, m), 4,51 (2H, s), 7,20 (1H, d, J=8.1 Hz), 7,31 (1H, d, J=8.1 Hz), 7,73 (1H, DD, J=8,1 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 388 (M+H).

Compound 5t-0-10:

Ethyl ester of 2-(2-(di-tert-butyloxycarbonyl)aminopyridine-4-ylmethyl)-3-oxomalonate acid

Chemical formula 149

Ethylacetoacetate (109,6 μl, 0.86 mmol) was dissolved in THF (2.0 ml) and to the mixture was added 2-(di-tert-butoxycarbonyl)amino-4-(methyl bromide)pyridine (which was obtained by a method described in Bioorganic & Medicinal Chemistry Letters 2004, 14, 2227-2231) and NaH (39,0 mg, 0.97 mmol). The mixture was stirred at room temperature for 12 hours Then the reaction solution was added water and the solution was extracted with ethyl acetate. After washing with sodium bicarbonate solution and saturated salt solution the organic layer was dried over anhydrous magnesium sulfate and the solvent is kept at reduced pressure. The obtained residue was purified column chromatography on silica gel with obtaining specified in the connection header (206,2 mg, 83%).

1H NMR (CDCl3, 270 MHz) δ (ppm): 1,22 (3H, t, J=6,7 Hz), 1,31-of 1.39 (18H, m), of 2.23 (3H, s), 3,17 (1H, DD, J=8,1, 5,4 Hz), of 3.78 (1H, DD, J=8.1 Hz), 4,10-4,22 (2H, m), 7,02 (1H, d, J=5.4 Hz), 7,05 (1H, users), of 8.37 (1H, d, J=5,4 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 437 (M+H).

Connect the tion 5t-0-13:

Ethyl ester of 2-(2-(di-tert-butyloxycarbonyl)aminopyridine-6-ylmethyl)-3-oxomalonate acid

Chemical formula 150

Specified in the title compound was synthesized under the same conditions described in example obtain compound 5t-0-10, except that the compound 5c-0-13 used instead of 2-(di-tert-butoxycarbonyl)amino-4-(methyl bromide)pyridine.

1H NMR (CDCl3, 270 MHz) δ (ppm): 1,22 (3H, t, J=6,7 Hz), 1,31-of 1.39 (18H, m), 3,20-3,44 (2H, m), 4,11-to 4.28 (3H, m), 7,06 (1H, d, J=8.1 Hz), 7,10 (1H, d, J=8.1 Hz), 7,63 (1H, DD, J=8,1 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 437 (M+H).

Compound 5d-0-12:

3-(2-Aminopyridine-4-ylmethyl)-6-chloro-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

Chemical formula 151

Compound 5t-0-10 (180,9 mg, 414 μmol) and 4-chlororesorcinol (71,9 mg, 497,3 mmol) was stirred in concentrated sulfuric acid (66,3 μl, of 1.24 mmol) at room temperature for 24 h Then the reaction solution was added ethyl acetate and the solution washed with sodium bicarbonate solution and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate and the solvent is kept at reduced pressure. The obtained residue was purified column chromatography on silica gel (mixture of methylene chloride:methanol = 5:1) to obtain what is shown in the connection header (28,0 mg).

1H-NMR (CD3OD, 270 MHz) δ (ppm): at 2.36 (3H, s), a 3.87 (2H, s)6,41 (1H, users), 6,51 (1H, d, J=5.4 Hz), 6,69 (1H, s), 7,66 (1H, s), of 7.75 (1H, d, J=5.4 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 317 (M+H).

Compound 5d-0-10:

3-(2-Aminopyridine-4-ylmethyl)-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

Chemical formula 152

Specified in the title compound was obtained from compound 5t-0-10 and resorcinol in the same conditions described in example obtaining compounds 5d-0-12.

1H-NMR (300 MHz) (DMSO-d6) δ (ppm): 2,35 (3H, s), 3,76 (2H, s), USD 5.76 (2H, users), of 6.20 (1H, s), 6.35mm (1H, d, J=5,34 Hz), 6,72 (1H, d, J=2,29 Hz), PC 6.82 (1H, DD, J=2,67, 8,77 Hz), the 7.65 (1H, d, J=8,77 Hz), of 7.75 (1H, d, J=5,34 Hz), 10,46 (1H, users).

MC (Micromass, Quattromicro, ESI+) m/z: 282,87 (M+H).

Compound 5d-0-11:

3-(2-Aminopyridine-4-ylmethyl)-6-fluoro-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

Chemical formula 153

Specified in the title compound was obtained from compound 5t-0-10V and 4-forreporting in the same conditions described in example obtaining compounds 5d-0-12.

1H-NMR (300 MHz) (DMSO-d6) δ (ppm): 2,35 (3H, s), 3,76 (2H, s), 5,74 (2H, users), to 6.19 (1H, s)6,34 (1H, d, J=5,72 Hz), make 6.90 (1H, d, J=7,63 Hz), only 6.64 (1H, d, J=11,83 Hz), of 7.75 (1H, d, J=5,34 Hz), 11,02 (1H, users).

Compound 5d-0-13:

3-(2-Aminopyridine-6-ylmethyl)-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

Chemical formula is 154

Specified in the title compound was obtained from compound 5t-0-13 and resorcinol in the same conditions described in example obtaining compounds 5d-0-12.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.42 (3H, s), 3,82 (2H, s), 5,75-to 5.85 (2H, m), 6,10-of 6.20 (2H, m), 6,70 (1H, users), is 6.78 (1H, d, J=8.1 Hz), 7.23 percent (1H, DD, J=8.1 Hz), to 7.64 (1H, d, J=8,1 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 283 (M+H).

Compound 5d-0-14:

3-(2-Aminopyridine-6-ylmethyl)-6-fluoro-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

Chemical formula 155

Specified in the title compound was synthesized from compound 5t-0-13 and 4-forreporting in the same conditions described in example obtaining compounds 5d-0-12.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): of 2.38 (3H, s), 3,82 (2H, s), 5,78 (2H, users), to 6.22 (1H, d, J=7,6 Hz), and 6.25 (1H, d, J=7,6 Hz), 6.89 in (1H, d, J=7.5 Hz), 7.23 percent (1H, t, J=7,6 Hz), a 7.62 (1H, d, J=11,9 Hz), and 11.0 (1H, users).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 301 (M+H).

Compound 5d-0-15:

3-(2-Aminopyridine-6-ylmethyl)-6-chloro-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

Chemical formula 156

Specified in the title compound was synthesized from compound 5t-0-13 and 4-chlororesorcinol in the same conditions described in example obtaining compounds 5d-0-12.

1H-NMR (DMSO-d6 , 270 MHz) δ (ppm): of 2.38 (3H, s), 3,82 (2H, s)5,80 (2H, users), 6,24 (1H, d, J=7,6 Hz), 6,27 (1H, d, J=7,6 Hz), 6.89 in (1H, s), 7.23 percent (1H, t, J=7,6 Hz), 7,78 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 317 (M+H).

Compound 5d-0-16:

3-(3-fluoro-2-aminopyridine-4-ylmethyl)-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized from compound 5t-0-16A and resorcinol in the same conditions described in example obtaining compounds 5d-0-12.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): is 2.37 (3H, s), 3,86 (2H, s), 6,16 (2H, users), 6,23 (1H, DD, J=5,1 Hz)6,91 (1H, s), 7,60 (1H, d, J=5,1 Hz), the 7.85 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 301 (M+H).

Compound 5d-0-17:

3-(3-fluoro-2-aminopyridine-4-ylmethyl)-7-hydroxy-6-fluoro-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized from compound 5t-0-16A and 4-forreporting in the same conditions described in example obtaining compounds 5d-0-12.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): at 2.36 (3H, s), 3,86 (2H, s), 6,10 (2H, usher.), 6,23 (1H, DD, J=5,1 Hz), 6.89 in (1H, d, J=6.6 Hz), EUR 7.57 (1H, d, J=5,1 Hz), the 7.65 (1H, d, J=12 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 319 (M+H).

Compound 5d-0-18:

3-(3-fluoro-2-aminopyridine-4-ylmethyl)-7-hydroxy-6-chloro-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized from compound 5t-0-16A and 4-chlororesorcinol in the same conditions described in example obtaining compounds 5d-0-12.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2.40 a (ZN, C), 3,86 (2H, s), 6,36 (1H, DD, J=5,1 Hz)6,91 (1H, s), 7,60 (1H, d, J=5,1 Hz), the 7.85 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 335 (M+H).

Compound 5d-0-19:

3-(3-fluoro-2-aminopyridine-4-ylmethyl)-7-hydroxy-6-methyl-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized from compound 5t-0-16A and 4-methylresorcinol in the same conditions described in example obtaining compounds 5d-0-12.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 2,19 (3H, s), is 2.37 (3H, s), 3,85 (2H, s)6,09 (2H, users), 6,21 (1H, DD, J=5,1 Hz), of 6.71 (1H, s), 7,54 (1H, s), 7,56 (1H, d, J=5,1 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 315 (M+H).

Compound 5d-0-me:

3-(2-Amino-3-herperidin-4-ylmethyl)-4-ethyl-7-hydroxy-6-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized from compound 5t-0-16b and 4-methylresorcinol in the same conditions described in example obtaining compounds 5d-0-12.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 1,06 (2H, t, J=7.4 Hz), measuring 2.20 (3H, s), and 2.79 (2H, userc, J=7,4 Hz), 3,83 (2H, s), 6,10 (2H, s), of 6.20 (1H, t, J=5,1 Hz), to 6.75 (1H, s), 7,55 (1H, s), EUR 7.57 (1H, d, J=5,1 Hz), 10,50 (1H, s).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 329 (M+H).

Compound 5d-0-4S1:

3-(2-Fluoro-3-aminobenzyl)-7-mercapto-4-methyl-2-oxo-2H-1-benzopyran

152 mg (1,21 mmol) 3-hydroxybenzoyl and 153 mg (0,60 mmol) ethyl ester 2-(2-fluoro-3-aminobenzyl)-3-oxomalonate acid was added to polyphosphoric acid (6 g) and the mixture was stirred at 70°C for 2.5 h Then the reaction mixture was added water and the precipitated precipitated solid was filtered. The obtained solid was purified column chromatography on silica gel (mixture of dichloromethane:methanol) = 50:1 to 20:1) to give 12 mg (1%) of compound 5d-0-4S1 in the form of a pale yellow powder.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 316 (M+H).

Compound 5d-7-4S2:

3-(2-Fluoro-3-aminobenzyl)-7-metiloksi-4-methyl-2-oxo-2H-1-benzothiophen

Specified in the title compound was synthesized using 3-methoxybenzoyl and ethyl ester of 2-(2-fluoro-3-aminobenzyl)-3-oxomalonate acid under the same conditions described in example obtaining compounds 5d-0-4S1.

1H NMR (CDCl3, 270 MHz) δ (ppm): to 2.46 (3H, s), 3,70 (2H, users), 3,88 (3H, s), of 4.12 (2H, s), to 6.39 (1H, DDD, J=8,1 Hz, 1.3 Hz, JHF=8.1 Hz), is 6.61 (1H, DDD, J=8,2 Hz, 1.4 Hz, JHF=8,2 Hz), 6,77 (1H, DD, J=7.9 Hz, 7.9 Hz), ,91 (1H, d, J=2.6 Hz), of 6.96 (1H, DD, J=9.1 Hz, 2.6 Hz), 7,80 (1H, d, J=9.1 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 330 (M+H).

Compound 5d-0-4S2:

3-(2-Fluoro-3-aminobenzyl)-7-hydroxy-4-methyl-2-oxo-2H-1-benzothiophen

13.5 mg level (0.041 mmol) of compound 5d-7-4S2 was dissolved in dichloromethane (1 ml) and to the solution was added 410 μl (0.41 mmol) of a solution of tribromide boron with a concentration of 1 mol/l in dichloromethane. The mixture was stirred in nitrogen atmosphere for 18 hours Then the reaction mixture was added water and the precipitated precipitated solid was filtered to obtain a 7.6 mg (59%) of compound 5d-0-4S2 in the form of a white powder.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.42 (3H, s), of 3.95 (2H, s), 5,61 (2H, users), 6,07 (1H, DDD, J=7,2 Hz, 1.1 Hz, JHF=7,2 Hz), to 6.58 (1H, DDD, J=8,2 Hz, 1.2 Hz, JHF=8,2 Hz), 6,69 (1H, DD, J=8,2 Hz, 7.2 Hz), 6,80-6,62 (2H, m), to $ 7.91 (1H, d, J=9.7 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 316 (M+H).

Compound 5C-0-53:

N-(3-mercaptophenyl)ndimethylacetamide

3-Aminothiophenol (1.0 g, to 7.99 mmol), acetic anhydride (0,83 ml) and triethylamine (1.7 ml) was dissolved in methylene chloride and the solution was stirred at room temperature for 2 hours Then purified by chromatography on silica gel (hexane:ethyl acetate = 3:1) to obtain specified in the connection header (1,16 g, 87%).

1 H NMR (300M Hz, CDCl3) δ (ppm): 7,18 (1H, t, J=7,6 Hz), to 6.80 (1H, d, J=7,6 Hz), 6.75 in (1H, m), of 6.71 (1H, DD, J=2.3 Hz, 8.0 Hz), and 3.72 (2H, user. C)to 2.40 (3H, s).

MS (ESI+) m/z: 167,91 (M+H).

Compound 5t-0-53:

Ethyl ester of 2-(3-acetaminophenol)3-oxomalonate acid

Compound 5C-0-53 (600 mg and 3.59 mmol) and ethyl ester of 2-chloro-3-oxomalonate acid (0,50 ml) was dissolved in methylene chloride (6 ml) and triethylamine (0,52 ml) slowly dropwise added to the reaction mixture at 0°C. the Mixture was heated to room temperature and was stirred overnight. Then it was purified by chromatography on silica gel (hexane:ethyl acetate = 5:1) to obtain the specified title compound (181 mg, 17%).

1H NMR (300M Hz, CDCl3) δ (ppm): 11,8 (1H, s), 7,24 (1H, m), 7,01 (1H, m), 6.87 in (2H, m), 4,1 (3H, m), and 2.27 (6H, s)of 1.18 (3H, m).

MS (ESI+) m/z: 294,99 (M).

Compound 5d-0-53:

3-(3-Aminothiophene)-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

Compound 5t-0-53 (163 mg, 0,552 mmol) and resorcinol (61 mg) was mixed with 70% sulfuric acid (0.5 ml) under cooling on ice and the mixture was heated to room temperature and was stirred overnight. The reaction mixture was added to water with ice and the resulting solid was filtered to obtain specified in the title compound (149 mg, 90%).

1H-NMR (300 MHz, DMSO-d6) δ (ppm): to 10.7 (1H, s), 7,74 (1H, d, J=8,8 Hz), 6,93 (1H, t, J=8.0 Hz), 6,86 (1H, DD, J=2.3 Hz, J=8,4 Hz), 6,74 (1H, d, J=2.3 Hz), 6,37 (3H, m), 5,59 (2H, user. C)to 2.66 (3H, s).

MS (ESI+) m/z: 300,08 (M + H).

Compound 5t-0-52:

Ethyl ester of 2-(3-acetaminophenol)-3-hydroxybutyric acid

A solution of 3-acetylaminophenol (1 g, of 6.61 mmol) in tetrahydrofuran (3.3 ml) was added to a mixture of NaH (264 mg) and tetrahydrofuran (2.6 ml) at 0°C. the Mixture was stirred at room temperature for 1 h and then to the mixture was added tetramethylaniline (1.0 ml) and ethyl ester of 2-chloro-3-oxomalonate acid (1.0 ml). The mixture was boiled under reflux for 8 h and was purified by chromatography on silica gel (mixture of methylene chloride:methanol = 50:1) to obtain the specified title compound (210 mg, 11%).

1H NMR (300M Hz, CDCl3) δ (ppm): 7,34 (1H, s), 7,29 (1H, s), 7,21 (2H, m),? 7.04 baby mortality (1H, d, J=7,6 Hz), of 6.65 (1H, DD, J=2.3 Hz, J=8,4 Hz), 5,09 (1H, s), 4,29, (2H, q, J=7.2 Hz), of 2.38 (3H, s)of 2.16 (3H, s)of 1.29 (3H, t, J=6,9 Hz).

MS (ESI+) m/z: 280,05 (M+H).

Compound 5d-0-R:

3-(3-Acetylaminophenol)-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized using compound 5t-0-52 and resorcinol in the same conditions described in example obtaining compounds 5d-0-53.

1H-NMR (300 MHz, DMSO-d6) δ (ppm): 10,5 (1H, s), to 9.91 (1H, s), 7,66 (1H, d, J=8,8 Hz), 7.23 percent (3H, m), 6.89 in (1H, DD, J=2.3 Hz, J=8,8 Hz), 6,79 (1H, d, J=2.3 Hz), of 6.66 (1H, m)to 2.29 (3H, s)to 1.99 (3H, s).

MS (ESI+) m/z: 326,02 (M+H).

Compound 5d-0-52:

3-(3-Aminophenoxy)-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized using compound 5t-0-52 and resorcinol in the same conditions described in example obtaining compounds 5d-0-53.

1H-NMR (300 MHz, DMSO-d6) δ (ppm): to 7.61 (1H, m)6,91 (1H, m), 6,85 (1H, m), 6,74 (1H, m), 6,21 (1H, J=8,4 Hz), between 6.08 (2H, m), 5,12 (2H, user. C), and 2.26 (3H, s).

MS (ESI+) m/z: 283,97 (M+H).

Compound 5t-0-74:

Ethyl ester of 2-(2-acetylaminophenol-4-ylmethyl)-3-hydroxybutyric acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1C-2, except that 2-acetylamino-4-chloromethylthiazole used instead of 1-bromomethyl-2-fluoro-3-nitrobenzene.

1H-NMR (Bruker (ARX-300), CDCl3) δ (ppm): 9,42 (1H, s), a 9.60 (1H, s), 4,21-to 4.14 (2H, m), of 3.94 (1H, t, J=7.4 Hz), 3,19 (2H, HF), 2,24 (3H, s), of 2.23 (3H, s)of 1.23 (3H, t, J=7,1 Hz).

Compound 5d-0-R:

3-(2-Acetylaminophenol-4-ylmethyl)-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized using compound 5t-0-74 in the same conditions described in example obtaining compounds 5d-0-12. It was isolated by chromatography on Sealy is agile as separate fractions of compounds 5d-0-74.

1H-NMR (Bruker (ARX-300), DMSO-d6) δ (ppm): of $ 11.97 (1H, s), 10,42 (1H, s), 7,42 (1H, d, J=8,4), to 6.80 (1H, DD, J=9.0 Hz, J=2.4 Hz), 6,72 (1H, s)6,70 (1H, d, J=2.7 Hz), 3,90 (2H, s), of 2.38 (3H, s), of 2.08 (3H, s).

Compound 5d-0-74:

3-(2-Aminothiazol-4-ylmethyl)-7-hydroxy-4-methyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized using compound 5t-0-74 in the same conditions described in example obtaining compounds 5d-0-12. It was isolated by chromatography on silica gel in the form of individual fractions of compounds 5d-0-R.

1H-NMR (Bruker (ARX-300), CDCl3) δ (ppm): the 10.40 (1H, s), 7,63 (1H, d, J=9.0 Hz), for 6.81 (2H, s), 6,79 (1H, DD, J=9,3 Hz, J=2.7 Hz), 6,69 (1H, d, J=2.1 Hz), 6,04 (1H, s), 3,71 (2H, s), of 2.38 (3H, s).

A common way-6

The following are examples of the preparation related to General method 6, which was mentioned earlier.

Compound 6b-1-4:

4-methyl bromide-3-(2-fluoro-3-nitrobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 157

THF (0.9 ml) was added to 3-(2-fluoro-3-nitrobenzyl)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid (compound 1g-1-4) (47,6 mg) and the resulting suspension was stirred at -78°C for 20 min to obtain a dark brown solution. This solution was added at 0°C. to a solution of N-bromosuccinimide (28 mg) in THF (0.8 ml) (which was prepared by the in advance in a separate container) and the mixture was stirred at 0°C for 40 minutes This reaction solution was poured into 1 N hydrochloric acid (0,119 ml), diluted with water with ice (20 ml)and then extracted with ethyl acetate. The organic extract was washed with saturated salt solution and the organic layer was dried over anhydrous magnesium sulfate. The solvent is kept under reduced pressure and the obtained residue was purified by thin-layer chromatography on silica gel (hexane:ethyl acetate = 1:1) to obtain the specified title compound (24.3 mg).

1H NMR (CDCl3, 270 MHz) δ (ppm): 3.04 from (3H, s), of 3.13 (3H, s)to 4.15 (2H, s), to 4.62 (2H, s), 7,11-to 7.35 (3H, m), 7,62-7,76 (1H, m), the 7.65 (1H, DDD, J=9,0, to 8.2, 1.8 Hz), 7,71 (1H, d, J=9.5 Hz), 7,92 (1H, DDD, J=9,0, to 8.2, 1.8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 479 (M), 481 (M+2H).

Compound 6b-1-1:

4-methyl bromide-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 158

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 6b-1-4, except that the compound 1g-1-1 was used instead of compound 1g-1-4.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 2.94 (3H, s), of 3.07 (3H, s), 4,20 (2H, s), 5,07 (2H, s), 7,25 (1H, DD, J=8,7, and 2.3 Hz), 7,30 (1H, d, J=2.3 Hz), 7,58 (1H, t, J=8.1 Hz), to 7.77 (1H, userd, J=8.1 Hz), of 7.96 (1H, d, J=8.7 Hz), 8,05-8,13 (1H, m), by 8.22 (1H, t, J=1.9 Hz).

ESI (LC/MS in the mode register is the positively charged ions) m/z: 502 (M + acetonitrile), 504 (M + acetonitrile + 2N).

Compound 6b-1-2:

4-methyl bromide-6-fluoro-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 159

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 6b-1-4, except that the compound 1g-1-2 was used instead of compound 1g-1-4.

1H NMR (CDCl3, 270 MHz) δ (ppm): 3,05 (3H, s)and 3.15 (3H, s), 4,18 (2H, s), 4,50 (2H, s), 7,45-of 7.55 (2H, m), 7,66 (1H, d, J=8.1 Hz), 8,05-to 8.20 (2H, m).

One of the proton peaks of the benzene ring overlap with the peak of the CDCl3.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 479 (M), 481 (M+2H).

Compound 6b-1-3:

6-Chloro-4-methyl bromide-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 160

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 6b-1-4, except that the compound 1g-1-3 was used instead of compound 1g-1-4.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): by 8.22 (s, 1 H), of 8.15 (s, 1H), of 8.09 (d, J=8,1 Hz, 1H), to 7.77 (d, J=8,2 Hz, 1H), 7,58 (t, J=7.9 Hz, 1H), 7,50 (s, 1H), 5,11 (s, 2H), is 4.21 (s, 2H), 3,11 (s, 3H), 2.95 and (s, 3H).

ESIMC m/z: 497 (M+H).

Compound 6b-2-4:

4-methyl bromide-3-(2-fluoro-3-nitrobenzyl)-7-(Piri is one-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 161

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 6b-1-4, except that the compound 1g-2-4 was used instead of compound 1g-1-4.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 8,70 (d, J=4.9 Hz, 2H), 8,05-of 8.00 (m, 2H), 7,63 (t, J=6,4 Hz, 1H), 7,45 (d, J=2.4 Hz, 1H) 7,40-7,30 (m, 3H), of 5.03 (s, 2H), 4.16 the (s, 2H).

ESIMC m/z: 486 (M+H).

Compound 6C-1-4:

4-Vermeil-3-(2-fluoro-3-nitrobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 162

Acetonitrile (1.0 ml) was added to 4-methyl bromide-3-(2-fluoro-3-nitrobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid (compound 6b-1-4) (24,0 mg) and the resulting suspension was added potassium fluoride (3.1 mg) and 18-crown-6-ether (13.2 mg) under stirring at room temperature. The mixture was stirred at 60°C for 4 h, then the reaction solution was added potassium fluoride (3.1 mg) and 18-crown-6-ether (13.2 mg) and the mixture was additionally stirred at 60°C. for 1.5 hours, This reaction solution was poured into 1 N hydrochloric acid (0,110 ml), diluted with water with ice (20 ml)and then extracted with ethyl acetate. The resulting organic extract was washed with saturated salt solution and the organic layer was dried over betw denim magnesium sulfate. The solvent is kept under reduced pressure and the obtained residue was purified by thin-layer chromatography on silica gel (hexane:ethyl acetate = 1:1) to obtain specified in the connection header (14,7 mg).

1H NMR (CDCl3, 270 MHz) δ (ppm):3,03 (3H, s), of 3.13 (3H, s), 4,17 (2H, s), of 5.75 (2H, d, J=46,8 Hz), 7,11-7,20 (2H, m), 7,22 (1H, TD, J=8,2, 1.3 Hz), of 7.70 (1H, TD, J=8,2, 1,4 Hz), 7,78 (1 H, dt, J=7,4, 1.8 Hz), 7,92 (1H, DDD, J=8,2, 6,8, 1,4 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 419 (M+H).

Compound 6C-1-1:

4-Vermeil-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 163

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 6C-1-4, except that the compound 6b-1-1 was used instead of compound 6b-1-4.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): at 2.93 (3H, s), of 3.07 (3H, s)4,07 (2H, users), 5,88 (2H, d, J=46,3 Hz), 7.23 percent (1H, DD, J=8,7, and 2.3 Hz), 7,30 (1H, d, J=2.3 Hz), 7,58 (1H, t, J=8.1 Hz), 7,73 (1H, d, J=8.7 Hz), to 7.93 (1H, DD, J=for 8.1, 1.8 Hz), 8,02-to 8.12 (1H, m), 8,15 (1H, t, J=1,8 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 401 (M+H).

Compound 6C-1-2:

6-Fluoro-4-vermeil-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 164

Specified in C is the cylinder compound was synthesized in the same conditions, described in the example of a connection 6s-1-4, except that the compound 6b-1-2 was used instead of compound 6b-1-4.

1H NMR (CDCl3, 270 MHz) δ (ppm): 3,05 (3H, s)and 3.15 (3H, s), is 4.21 (2H, users), the 5.65 (2H, d, J=46,8 Hz), 7,45-the 7.65 (3H, m), 8,05-8,18 (2H, m).

One of the proton peaks of the benzene ring overlap with the peak of the CDCl3.

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 419 (M+H).

Compound 6C-1-3:

6-Chloro-4-vermeil-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 165

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 6C-1-4, except that the compound 6b-1-3 was used instead of compound 6b-1-4.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 8.12 (s, 1H), 8,09 (s+d, 2H), 7,72 (d, J=7.8 Hz, 1H), 7,58 (t, J=7.8 Hz, 1H), 7,56 (s, 1H), 5,95 (d, J=46,0 Hz, 2H), 4,22 (s, 2H), 3,11 (s, 3H), 2.95 and (s, 3H).

ESIMC m/z: 435 (M+H).

Compound 6C-2-4:

4-Vermeil-3-(2-fluoro-3-nitrobenzyl)-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 166

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 6C-1-4, except that the compound 6b-2-4 was used instead of compound 6b-1-4./p>

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 8,68 (d, J=4.9 Hz, 2H), 8,02-of 7.96 (m, 2H), 7.62mm (t, J=6 and 5 Hz, 1H), 7,43 (d, J=2.4 Hz, 1H) 7,35-7,29 (m, 3H), 5,91 (d, J=46.2 Hz, 2H), 4,18 (s, 2H).

ESIMC m/z: 426 (M+H).

Compound 6A-3-4-1R:

3-(2-Fluoro-3-{[1-penile-(Z)-ilidene]amino}benzyl-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 167

Methanol (4.0 ml) was added to 3-(3-amino-2-terbisil)-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran (compound 1h-3-4) (200 mg) and the resulting suspension was added benzaldehyde (0,053 ml) under stirring at room temperature. The suspension is boiled under reflux for 3 h Then the reaction solution was cooled to room temperature and the solvent drove away under reduced pressure. The obtained residue was purified by chromatography on silica gel (Aminogen) (dichloromethane) to obtain the specified title compound (233 mg).

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): Android 4.04 (2H, s), 6,92-7,20 (3H, m), 7,31-7,40 (4H, m), 7,45-of 7.60 (4H, m), to $ 7.91-of 8.00 (3H, m), 8,66 (1H, s).

The peak of CH3overlap with DMSO peak.

Compound 6b-3-4-1R:

4-methyl bromide-3-(2-fluoro-3-{[penile-(Z)-ilidene]amino}-benzyl)-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 168

THF (4.5 ml) was added to 3-(2-fluoro-3-{[1-penile-(Z)-ilidene]amino}benzyl-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-be soprano (compound 6A-3-4-1R) (226 mg) and the mixture was stirred at -78°C for 20 min and was further stirred at 0°C for 1 h to obtain a dark brown solution. This solution was added within 10 min to a solution of N-bromosuccinimide (178 mg) in THF (3.0 ml) (which was prepared in advance in a separate container) and the mixture was additionally stirred at 0°C for 1 h the Reaction solution was added water (5 ml) to complete the reaction and the solution was extracted with ethyl acetate. The resulting organic extract was washed with saturated salt solution and the organic layer was dried over anhydrous magnesium sulfate. The solvent is then drove away under reduced pressure and the obtained residue (320 mg)containing specified in the header of the connection.

Peak bromatology group was observed around σ 4,9 (ppm) when setting1H-NMR (270 MHz, CD3OD.

Compound 6C-3-4-1R:

4-Vermeil-3-(2-fluoro-3-aminobenzyl)-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Chemical formula 169

THF (5.0 ml) was added to the residue (315 mg)containing 4-methyl bromide-3-(2-fluoro-3-{[1-penile-(Z)-ilidene]amino}benzyl)-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran (compound 6b-3-4-1R)obtained in the previous reaction. To the resulting suspension were added potassium fluoride (84,0 mg) and 18-crown-6-ether (381 mg) under stirring at room temperature and the suspension is boiled under reflux for 2.5 hours After cooling to room temperature, to the mixture was added ethyl acetate and water and the mixture was extracted. the received organic extract was washed with saturated salt solution and the organic layer was dried over anhydrous magnesium sulfate. The solvent is kept under reduced pressure, the obtained residue was added ethyl acetate (3.0 ml) and 1 N hydrochloric acid (3.0 ml) and the mixture was stirred at room temperature for 10 minutes Then added ethyl acetate and saturated sodium bicarbonate solution and the mixture was extracted. The resulting organic extract was washed with saturated salt solution and the organic layer was dried over anhydrous magnesium sulfate. The solvent is kept under reduced pressure and the obtained residue was purified by chromatography on silica gel (hexane:ethyl acetate = 4:1 to 1:1) mixture (20.6 mg)containing specified in the header of the connection.

Peak permetrina group was observed around σ 5,5 (ppm) when setting1H-NMR (270 MHz, CDCl3).

General method 7

The following are examples of the preparation associated with the General method 7, which I mentioned earlier.

Compound 7C-1-ON:

6-Chloro-4-(2-hydroxyethyl)-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 170

LiHMDS (57,5 ml, 1.0 M solution in THF) was added in a nitrogen atmosphere at -78°C to a suspension of 6-chloro-4-methyl-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid (compound 1g-1-3) (20,0 g, 48,0 mmol) in anhydrous THF (250 ml) and the reaction mixture re exively at -78°C for 30 min and at 0°C for 30 minutes Then to the mixture was added paraformaldehyde (2,88 g, 96,0 mmol) and the mixture was stirred at room temperature overnight. Then the reaction mixture was poured into water and was extracted twice with ethyl acetate. The organic extract was washed with saturated salt solution and dried over magnesium sulfate. Received crude solid concentration in vacuum and washed with ethyl acetate to obtain specified in the title compound (18.5 g, 86%) as a white powder.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 8,10 (m, 2 H), of 8.06 (s, 1H), 7,65 (d, J=8,1 Hz, 1H), EUR 7.57 (t, J=8,1 Hz, 1H), 7,52 (s, 1H), 4,91 (t, J=5.4 Hz, 1H), 4.16 the (s, 2H), 3,63 (kV, J=5.4 Hz, 2H), 3,14 (m, 2H), 3,12 (s, 3H), 2,95 (s, 3H).

ESIMC m/z: 447 (M+H).

Compound 7d-1-ON:

6-Chloro-4-(2-hydroxyethyl)-3-(3-aminobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 171

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 7C-1-ONE was used instead of compound 1g-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm):of 8.04 (s, 1H), 7,49 (s, 1H), 6.90 to (t, J=8.0 Hz, 1H), 6,36 (m, 3H), 4,96 (s, 2H), 4,88 (t, J=5.4 Hz, 1H), a 3.87 (s, 2H), 3,60 (kV, J=5.4 Hz, 2H), 3,11 (s, 3H), 3.04 from (t, J=6.0 Hz, 2H), 2.95 and (s, 3H).

ESIMC m/z: 417 (M+H).

Compound 7C-1-ON:

4-(2-Hydroxyethyl)-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran the-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 7C-1-ON, except that the compound 1g-1-1 was used instead of compound 1g-1-3.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 8,13 (d, 1H, J=1.8 Hz), of 8.06 (DD, 1H, J=8,1, 1,4 Hz), to $ 7.91 (d, 1H, J=8.7 Hz), 7,73 (d, 1H, J=8,3 Hz), 7,58 (t, 1H, J=8.1 Hz), 7,27 (d, 1H, J=2.3 Hz), 7,20 (DD, 1H, J=8,7, 2,5 Hz), 4,91 (t, 1H, J=5.6 Hz), is 4.15 (s, 2H), 3,70 (m, 2H), 3,11 (m, 2H), of 3.07 (s, 3H), 2.95 and (s, 3H).

ESIMC m/z: 413 (M+H).

Compound 7d-1-ON:

4-(2-Hydroxyethyl)-3-(3-aminobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 7c-1-ONE was used instead of compound 1g-1-5.

1H NMR (CDCl3, 270 MHz) δ (ppm): a 7.62 (d, 1H, J=8.7 Hz), 7,25-7,00 (m, 3H), 6,70-6.42 per (m, 3H), 4.00 points (s, 2H), 3,71 (t, 2H, J=7,1 Hz), 3,20-3,10 (s+t, 5H), 3,03 (s, 3H).

ESIMC m/z: 383 (M+H).

Compound 7f-1-3CO:

6-Chloro-3-(3-nitrobenzyl)-2-oxo-4-(2-oxopropyl)-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 172

LiHMDS (11.5 ml, 1.0 M solution in THF) was added in a nitrogen atmosphere at -78°C to a suspension of 6-chloro-4-methyl-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimetic raminosoa acid (compound 1g-1-3) (4.0 g, a 9.60 mmol) in anhydrous THF (100 ml) and the mixture was stirred at -78°C for 30 min and at 0°C for 30 minutes Then to the mixture was added acetylchloride (1,36 ml, 19.2 mmol) and the mixture was stirred at room temperature for 1 h Then the reaction mixture was poured into water and was extracted twice with ethyl acetate. The organic extract was washed with saturated salt solution and dried over magnesium sulfate. Received crude solid concentration in vacuo and was purified column chromatography (mixture of ethyl acetate:hexane = 1:3) to obtain the specified title compound (1.28 g, 29%) as a white powder.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): to 8.12 (s, 1 H), with 8.05 (d, J=5.4 Hz, 1H), 7,92 (s, 1H), to 7.67 (d, J=8,1 Hz, 1H), 7,55 (t, J=8,1 Hz, 1H), 7,51 (s, 1H), of 4.44 (s, 2H), 4,07 (s, 2H), 3,10 (s, 3H), 2.95 and (s, 3H), and 2.27 (s, 3H).

ESIMC m/z: 459 (M+H).

Compound 7g-1-3CO:

6-Chloro-3-(3-aminobenzyl)-2-oxo-4-(2-oxopropyl)-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 173

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that compound 7f-1-3SD was used instead of compound 1g-1-5.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 7,89 (s, 1H), 7,53 (s, 1H), to 6.88 (t, J=8,1 Hz, 1H), 6,37-6,32 (m, 3H), USD 5.76 (s, 2H), 4,96 (s, 2H), 3,76 (s, 2H), 3,10 (s, 3H), 2.95 and (s, 3H), of 2.23 (s, 3H).

ESIMC m/: 429 (M+H).

Compound 7C-1-mean:

6-Chloro-4-(2-hydroxypropyl)-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Chemical formula 174

Sodium borohydride (49 mg, of 1.30 mmol) was added to a solution of 6-chloro-3-(3-nitrobenzyl)-2-oxo-4-(2-oxopropyl)-2H-1-benzopyran-7-silt ether dimethylcarbinol acid (compound 7f-1-3SD) (300 mg, of 0.65 mmol) in anhydrous THF (5.0 ml) and the mixture was stirred at 0° for 2 hours Then the reaction mixture was poured into water and was extracted with ethyl acetate. The organic extract was washed with saturated salt solution and dried over magnesium sulfate and indicated in the title compound (280 mg, 93%) was obtained as pale yellow powder.

1H-NMR (DMSO-d6, 270 MHz) δ (ppm): 8,12-with 8.05 (m, 3H), 7,71 (d, J=8,2 Hz, 1H), 7,60 is 7.50 (m, 2H), 4,88 (d, J=5.4 Hz, 1H), 4,22 (d, J=14 and 8 Hz, 1H), 4,11 (d, J=14,8 Hz, 1H), 3,86 (m, 1H), 3,11 (s, 3H), of 3.00 (m, 2H), 2.95 points (with, 3H), of 1.23 (d, J=5.5 Hz, 3H).

ESIMC m/z: 461 (M+H).

Compound 7f-1-SOON:

{3-(3-Nitrobenzyl)-7-dimethylcarbamoyl-2-oxo-2H-1-benzopyran-7-yl}acetic acid

Chemical formula 175

4-(2-Hydroxyethyl)-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid (compound 7C-1-ONE) was synthesized in the same conditions described in example obtaining compounds 7C-1-ON, except that Obedinenie 1g-1-1 was used instead of compound 1g-1-3.

To a solution of compound 7C-1-ONE (1.18 g, of 2.86 mmol) in acetone (25 ml) was added Jones reagent (3.2 ml, 2.67 Meters solution, 8,58 mmol) at 0°C and the mixture was stirred at room temperature for 30 minutes To the reaction mixture was slowly added 2-propanol until the disappearance of the red color and then it was poured into water and was extracted with ethyl acetate. The organic extract was washed with water and dried over magnesium sulfate. Specified in the title compound (865 mg, 71%) was obtained by concentration in vacuum in the form of a pale yellow powder.

1H-NMR (CDCl3, 270 MHz) δ (ppm): to 8.12 (s, 1H), 8,07 (d, J=8,2 Hz, 1H), 7,86 (d, J=8.6 Hz, 1H), 7,71 (d, J=8,2 Hz, 1H), 7,58 (t, J=7,6 Hz, 1H), 7,26 (d, J=2.1 Hz, 1H), 7,19 (DD, J=8,7, 2.2 Hz, 1H), 4,14 (s, 2H), 3,29 (, 2H), of 3.07 (s, 3 H), of 2.93 (s, 3H).

ESIMC m/z: 427 (M+H).

Compound 7f-1-SOON:

(3-(3-Nitrobenzyl)-6-chloro-7-dimethylcarbamoyl-2-oxo-2H-1-benzopyran-4-yl)acetic acid

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 7i-1-SOON, except that the compound 7c-1-ONE was used instead of compound 7C-1-ON.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): to 8.12 (s, 1H), 8,07 (d, 1H, J=Hz), 8,03 (s, 1H), 7,71 (d, 2H, J=8.1 Hz), EUR 7.57 (t, 1H, J=8,1 Hz) to 7.50 (s, 1H), 4,14 (s, 2H), or 3.28 (s, 2H), 3,10 (s, 3H), 2.95 and (s, 3H).

ESIMC m/z: 461 (M+H).

Compound 7f-1-Soome:

Methyl ester {3-(3-nitrobenzyl)-7-dim is tinkerbelleke-2-oxo-2H-1-benzopyran-4-yl}acetic acid

Chemical formula 176

Trimethylsilyldiazomethane (of 0.82 ml, 2.0 M solution in hexane) was added to a solution of {3-(3-nitrobenzyl)-7-dimethylcarbamoyl-2-oxo-2H-1-benzopyran-7-yl}acetic acid (compound 7f-1-SOON) (350 mg, 0.82 mmol) in methanol (5.0 ml)/dichloromethane (8.0 ml) and the mixture was stirred at room temperature for 10 minutes To the reaction mixture was added acetic acid (2.0 ml) and indicated in the title compound (338 mg, 94%) was obtained by concentration in vacuum in the form of a pale yellow powder.

1H-NMR (CDCl3, 270 MHz) δ (ppm): to 8.12 (s, 1H), 8,07 (d, J=8,2 Hz, 1H), 7,76 (d, J=8.7 Hz, 1H), of 7.70 (d, J=8,1 Hz, 1H), EUR 7.57 (t, J=7,6 Hz, 1H), 7,22 (s, 1H), 7,19 (d, J=8.5 Hz, 1H), 4,24 (s, 2H), 4.16 the (s, 2H), 3,50 (, 3H), 3,06 (s, 3H), of 2.93 (s, 3H).

ESIMC m/z: 441 (M+H).

Compound 7f-1-1NH2:

3-(3-Nitrobenzyl)-4-carbamoylmethyl-6-chloro-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

HODhbt (78 mg, 0.50 mmol) and WSC (91 mg, 0.50 mmol) was added to a solution of compound 7f-1-3COOH (185 mg, 0.40 mmol) in DMF (4.0 ml) and the mixture was stirred at room temperature for 2 hours To the reaction mixture was added dropwise NH3(0.33 M solution in THF and 6.1 ml, 2.00 mmol) and the resulting mixture was stirred at room temperature during the day and night. Then to the reaction mixture were added water and extraction was performed ethylacetate is. The organic extract was washed with saturated salt solution and dried over magnesium sulfate and then concentrated under reduced pressure to obtain specified in the title compound (170 mg, 93%) as a white solid.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 8,19 (s, 1H), of 8.06 (m, 1H), 7,98 (s, 1H), 7,76-of 7.70 (m, 2H), EUR 7.57 (t, 1H, J=8.1 Hz), 7,52 (s, 1H), 7,26 (s, 1H), 4,13 (s, 2H), 3.96 points (s, 2H), 3,10 (s, 3H), 2.95 and (s, 3H).

ESIMC m/z: 460 (M+H).

Compound 7g-1-3NH2:

3-(3-Aminobenzyl)-4-carbamoylmethyl-6-chloro-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 4A-0-4, except that the compound 7f-1-3CONH2was used instead of compound 1E-0-4.

1H-NMR (270 MHz, DMSO-d6) δ (ppm):8,00 (s, 1H), 7,68 (m, 1H), 7,56 (s, 1H), 7,25 (m, 1H), 6.90 to (t, 1H, J=8.1 Hz), 6,36 (m, 3H), 4,96 (s, 2H), 3,83 (s, 2H), 3,83 (s, 2H), 3,10 (s, 3H), 2.95 and (s, 3H).

ESIMC m/z: 430 (M+H).

Compound 7g-1-3N2:

3-(3-Aminobenzyl)-4-dimethylcarbamoyl-6-chloro-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

3-(3-Nitrobenzyl)-4-dimethylcarbamoyl-6-chloro-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid (compound 7g-1-3N2) was synthesized in the same the conditions, described in the example of a connection 7f-1-3N2except that dimethylamine was used instead of ammonia.

Specified in the title compound was synthesized under the same conditions described in example obtain compound 4A-0-4, except that the compound 7f-1-3CON2was used instead of compound 1E-0-4.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): to 7.84 (s, 1H), 7,49 (s, 1H), to 6.88 (m, 1H), 6,37-6,33 (m, 3H), is 4.93 (s, 2H), of 4.05 (s, 2H, in), 3.75 (s, 2H), 3,10 (s, 6H), 2.95 and (s, 3H), of 2.81 (s, 3H).

ESIMC m/z: 458 (M+H).

Compound 7C-1-one:

6-Chloro-4-methoxymethyl-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Potassium carbonate (279 mg, a 2.01 mmol) was added to a solution of 6-chloro-4-methyl bromide-3-(3-nitrobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid (compound 6b-1-3) (500 mg, 1.01 mmol) in THF (7.5 ml)/methanol (5.0 ml) and the mixture was stirred at room temperature for 2 h Then the reaction mixture was poured into water and was extracted with ethyl acetate. The organic extract was washed with saturated salt solution and dried over magnesium sulfate. The solvent drove by concentration under reduced pressure and the obtained residue was purified column chromatography to obtain specified in the title compound (40 mg, 10%) as a white solid prophetic is TBA.

1H-NMR (CDCl3, 270 MHz) δ (ppm): 8,14 (s, 1H), with 8.05 (d, 1H, J=8.1 Hz), 7,95 (s, 1H), of 7.70 (d, 1H, J=8.0 Hz), 7,47 (t, 1H, J=8.1 Hz), 7,27 (s, 1H), 4,71 (s, 2H), 4,13 (s, 2H), 3,48 (s, 3H), 3,17 (s, 3H), of 3.00 (s, 3H).

ESIMC m/z: 447 (M+H).

Compound 7d-1-one:

6-Chloro-4-methoxymethyl-3-(3-aminobenzyl)-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 4A-0-4, except that the compound 7C-1-some was used instead of compound 1E-0-4.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 8,00 (s, 1H), 7,51 (s, 1H), 6.90 to (t, 1H, J=8.0 Hz), 638-6,34 (m, 3H), to 4.98 (s, 2H), 4,71 (s, 2H), 3,90 (s, 2H), 3,37 (s, 3H), 3,10 (s, 3H), 2.95 and (s, 3H).

General method-8

The following are examples of the preparation associated with the General method-8, which was mentioned earlier.

Compound 8C-1:

(2-Chloro-3-herperidin-4-yl)methanol

2-Chloro-3-herperidin (1,51 ml, 14.9 mmol) was added in a nitrogen atmosphere at -78°C to a mixture of 2.0 M solution of diisopropylamide lithium (THF) (7,44 ml, 14.9 mmol) and THF (24 ml) and the mixture was stirred at 0°C for 2 hours To the mixture was added DMF (11,4 ml, 149 mmol) and the resulting mixture was stirred at 0°C for 2 hours Then to the mixture was added sodium borohydride (731 mg, and 19.3 mmol) and the mixture was stirred at 0°C for 1 h Then the reaction is ionic solution was added water, which then was extracted with ethyl acetate. The solution is washed with 1 N HCl solution, sodium bicarbonate solution and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate and the solvent is kept at reduced pressure. The obtained residue was purified column chromatography on silica gel with obtaining specified in the title compound (1.4 g, 58%).

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 4,65 (2H, d, J=5.8 Hz), 5,70 (1H, t, 5.8 Hz), 7,56 (1H, DD, J=4.6 Hz), of 8.27 (1H, d, J=4,6 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 162 (M+H).

Compound 8C-2:

4-(tert-Butyldimethylsilyloxy)-2-chloro-3-herperidin

A mixture of (2-chloro-3-herperidin-4-yl)methanol (200 mg, 1,24 mmol), imidazole (253 mg, 3.72 mmol) and tert-butyldimethylchlorosilane (373 mg, 2.48 mmol) in DMF was stirred at room temperature for 2 h Then the reaction solution was added methylene chloride and the solution was washed with a saturated solution of salt. The organic layer was dried over anhydrous magnesium sulfate and the solvent is kept at reduced pressure. The obtained residue was purified column chromatography on silica gel with obtaining specified in the title compound (319 mg, 93%).

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 0,12 (6H, s)0,86 (9H, s), to 4.87 (2H, s), 7,51 (1H, DD, J=4.9 Hz), 8,30 (1H, d, J=4.9 G is).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 276 (M+H).

Compound 8C-3:

Benzhydrylidene[4-(tert-butyldimethylsilyloxy)-3-herperidin-2-yl]amine

A mixture of 4-(tert-butyldimethylsilyloxy)-2-chloro-3-herperidin (30 mg, 108 μl), benzophenones (14 μl, 84 μmol), Tris(dibenzylideneacetone)diplegia(0) (7.7 mg, 8.4 μmol), (S)-(-)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (15.7 mg, to 25.3 mmol) and tert-butyl sodium (10.4 mg, 108 μmol) in toluene (0.5 ml) was stirred at 60°C over night. Then to the reaction solution were added ethyl acetate and the solution washed with sodium bicarbonate solution and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate and the solvent is kept at reduced pressure. The obtained residue was purified column chromatography on silica gel with obtaining specified in the title compound (27 mg, 60%).

1H NR (CD3OD, 270 MHz) δ (ppm): 0,00 (6H, s)0,86 (9H, s), 4,60 (2H, s), 5,42 (1H, s), 7,00-7,80 (11H, m), of 7.97 (1H, d, J=5,1 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 421 (M+H).

Compound 8C-4:

[2-(Benzhydrylidene)-3-herperidin-4-yl]methanol

The mixture benzhydrylidene[4-(tert-butyldimethylsilyloxy)-3-herperidin-2-yl]amine (14 mg, 32 µmol) and fluoride tetrobot is ammonia (1 mol/l in THF) (65 μl, 65 μmol) in THF (0.5 ml) was stirred at room temperature for 30 minutes Then to the reaction solution were added ethyl acetate and the solution washed with sodium bicarbonate solution and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate and the solvent is kept at reduced pressure. The obtained residue was purified column chromatography on silica gel with obtaining specified in the connection header.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 4,47 (2H, d, J=5.6 Hz), vs. 5.47 (1H, t, J=5.6 Hz),? 7.04 baby mortality-7,20 (3H, m), 7,25-7,40 (3H, m), 7,45 to 7.75 (5H, m), of 8.04 (1H, d, J=5.0 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 307 (M+H).

Compound 5t-0-16A:

Ethyl ester of 2-[2-(benzhydrylidene)-3-herperidin-4-ylmethyl]-3-oxomalonate acid

A mixture of [2-(benzhydrylidene)-3-herperidin-4-yl]methanol (compound 8C-4) (5 g, 16.3 mmol), methanesulfonamide (1,52 ml and 19.6 mmol) and tert-butyl lithium (in THF) (18 ml, 18 mmol) in THF (40 ml) was stirred at 0°C for 1 h the Mixture was added to a solution of ethyl ester of acetoacetic acid (4,16 ml, to 32.7 mmol), tert-butyl lithium (in THF) (19.6 ml of 19.6 mmol) and NaI (2.5 g, 16.3 mmol) in THF (18 ml). The solution was stirred at 50°C for 3 h, it was added 0.2 N LiOH solution (in water) and ethyl acetate and the solution was washed with 0.2 N LiOH solution (in water) and feast upon the s ' solution of salt. After drying over anhydrous magnesium sulfate, the solvent is kept at reduced pressure to obtain specified in the connection header (6,98 g, quantitative yield).

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 1,10 (3H, t, J=7,0 Hz)by 2.13 (3H, s), 2,90 was 3.05 (2H, m), of 3.94 (1H, t, J=7,7 Hz), of 4.05 (2H, q, J=7.0 Hz), 6,91 (1H, DD, J=4.3 Hz), 7,05-to 7.15 (2H, m), 7,30 to 7.75 (8H, m), to 7.93 (1H, d, J=4.3 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 419 (M+H).

Compound 5t-0-16Meb:

Ethyl ester of 2-(2-amino-3-herperidin-4-ylmethyl)-3-oxopentanoic acid

Specified in the title compound was synthesized by conducting the reaction under the same conditions described in example obtain compound 5t-0-16A, except that ethylbromoacetate used instead of the ethyl ester of acetoacetic acid and then spent removing protection using 3 N HCl solution.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): of 0.91 (3H, t, J=7,3 Hz)of 1.11 (3H, t, J=7,1 Hz), 2,50-2,61 (2H, m), 2,94-to 3.02 (2H, m), 3,98-4,12 (3H, m), 6,10 (2H, s), to 6.39 (1H, t, J=5,1 Hz), to 7.61 (1H, d, J=5,1 Hz).

ESI (LC/MS in the registration mode, the positively charged ions) m/z: 269 (M+H).

Compound 5d-0-Me:

7-Hydroxy-3,4-dimethyl-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtaining soedinenie-0-4, except that ethyl-2-methylacetoacetate was used instead of compound 1C-2.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 10,36 (s, 1H), to 7.61 (d, 1H, J=8.7 Hz), 6,79 (DD, 1H, J=8,7, 2,5 Hz), of 6.68 (d, 1H, J=2.5 Hz), was 2.34 (s, 3H), of 2.05 (s, 3H).

ESIMC m/z: 191 (M+H).

Compound 1h-3-Me:

3,4-Dimethyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-3-3, except that 7-hydroxy-3,4-dimethyl-2-oxo-2H-1-benzopyran (compound 5d-0-IU) was used instead of compound 1E-0-3.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 7,89 (d, 1H, J=9.1 Hz), was 7.45 (d, 1H, J=2.5 Hz), of 7.36-to 7.32 (m, 3H), 2,42 (s, 3H), 2.13 and (s, 3H).

ESIMC m/z: 274 (M+H).

Compound 1h-3-CH2Br:

3-methyl bromide-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

N-Bromosuccinimide (1,17 g, 6,59 mmol) and AIBN (45 mg, 0.27 mmol) was added to a solution of compound 1h-3-IU (1.50 g, 5,49 mmol) in carbon tetrachloride (80 ml) and the mixture was stirred at 75°C for 2 hours the Solvent drove by concentration under reduced pressure and the obtained residue was purified column chromatography (mixture of ethyl acetate:hexane = 1:2) to obtain the specified title compound (1.25 g, 65%) as a white solid.

1H-NMR (270 MHz, DMSO-d6) δ (ppm):to 7.99 (d, 1H, J=8.7 Hz), 7,51 (d, 1H, J=2.5 Hz), 7,41 (d, 1H, J=2.5 Hz), 7,38 (m, 2H), and 4.68 (s, 2H), 2,54 (s, 3H).

ESIMC m/z: 354 (M+H).

Compound 1h-3-R:

N-(2-(4-Methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran-3-ylethoxy)phenyl)ndimethylacetamide

o-Acetamidophenol (118 mg, 0.78 mmol) and potassium carbonate (118 mg, 0.85 mmol) was added to a solution of compound 1h-3-CH2Br (250 mg, 0.71 mmol) in THF (5.0 ml) and the mixture was stirred at 40°C for 2 h Then the reaction mixture was poured into water and extraction was performed with ethyl acetate. The organic extract was washed with saturated salt solution and dried over magnesium sulfate and then concentrated under reduced pressure to get crude product. The residue was purified column chromatography (mixture of ethyl acetate:hexane = 1:2) to obtain the specified title compound (100 mg, 33%) as a white solid.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 8,97 (s, 1H), 8,02 (d, 1H, J=8.7 Hz), of 7.97 (d, 1H, J=9.6 Hz), 7,53 (d, 1H, J=2.5 Hz), 7,40 (DD, 1H, J=8,9 and 2.5 Hz), 7,37 (s, 2H), 7,25 (d, 1H, J=6,8 Hz), was 7.08 (t, 1H, J=8,2 Hz), to 6.95 (t, 1H, J=7,3 Hz), 5,10 (s, 2H), has 2.56 (s, 3H), 2,04 (s, 3H).

ESIMC m/z: 423 (M+H).

Compound 1h-3-57:

3-(2-Aminophenoxy)-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Concentrated sulfuric acid was added to a solution of compound 1h-3-R (85 mg, 0.20 mmol) in ethanol (3.0 ml), THF (3.0 ml) and water (0.5 ml)and the mixture per Merivale at 75°C for 3 hours Then the reaction mixture was neutralized with saturated sodium bicarbonate solution and was extracted with ethyl acetate. The organic extract was washed with saturated salt solution and dried over magnesium sulfate and then concentrated under reduced pressure to get crude product. The residue was purified preparative IHMS obtaining specified in the title compound (30 mg, 39%) as a pale yellow solid.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): to 7.99 (d, 1H, J=8,9 Hz), 7,52 (m, 1H), 7,41 (m, 1H), 7,38-7,35 (m, 3H), of 6.96 (d, 1H, J=8.1 Hz), 6,70 (d, 1H, J=7.4 Hz), 6,63 (d, 1H, J=7,6 Hz), of 6.52 (t, 1H, J=7,6 Hz), 5,02 (s, 2H), 4,71 (s, 2H), by 2.55 (s, 3H).

ESIMC m/z: 381 (M+H).

Compound 1j-3-57-2:

3-(2-(Methylaminomethyl)aminophenoxy)-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-2, except that the compound 1h-3-57 was used instead of compound 1h-1-3.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): to 8.41 (s, 1H), 8,02 (d, 1H, J=8,9 Hz), 7,53 (d, 1H, J=2.3 Hz), 7,39 (m, 4H), 7,22 (DD, 1H, J=8,2, 1.2 Hz), 7,10 (m, 2H), 6,94 (TD, 1H, J=7,7, 1.3 Hz), to 5.08 (s, 2H), has 2.56 (s, 3H), 2,41 (d, 3H, J=4,9 Hz).

ESIMC m/z: 474 (M+H).

Compound 1h-3-R:

N-(3-((4-Methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran-3-ylmethyl)amino)phenyl)ndimethylacetamide

m-And acylaminoalkyl (118 mg, 0.78 mmol) and potassium carbonate (118 mg, 0.85 mmol) was added to a solution of compound 1h-3-CH2Br (250 mg, 0.71 mmol) in THF (5.0 ml) and the mixture was stirred at 75°C for 3 h Then the reaction mixture was poured into water and extraction was performed with ethyl acetate. The organic extract was washed with saturated salt solution and dried over magnesium sulfate and then concentrated under reduced pressure to get crude product. The residue was purified column chromatography (mixture of ethyl acetate:hexane = 1:2) to obtain the specified title compound (110 mg, 37%) as a white solid.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 9,68 (s, 1H), 7,95 (d, 1H, J=8,9 Hz), 7,49 (d, 1H, J=2.5 Hz), 7,39-7,34 (m, 3H), 7,02 (s, 1H), 6,97 (d, 1H, J=7.9 Hz), 6.73 x (d, 1H, J=7,6 Hz), 6,33 (d, 1H, J=8,2 Hz), 5,72 (t, 1H, J=4,9 Hz), 4,12 (d, 2H, J=4,9 Hz), of 2.51 (s, 3H).

ESIMC m/z: 422 (M+H).

Compound 1h-358 for:

3-((3-Aminophenylamino)methyl)-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Concentrated sulfuric acid (0.5 ml) was added to a solution of compound 1h-3-R (92 mg, 0,218 mmol) in ethanol (4.0 ml), THF (4.0 ml) and water (1.0 ml)and the mixture was stirred at 75°C for 2 h Then the reaction mixture was neutralized with saturated sodium bicarbonate solution and was extracted with ethyl acetate. The organic extract was washed with saturated salt solution and dried over magnesium sulfate and then con who was interaval under reduced pressure to get crude product. The residue was purified preparative IHMS obtaining specified in the title compound (38 mg, 46%) as a pale yellow solid.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 7,94 (d, 1H, J=8,9 Hz), 7,49 (d, 1H, J=2.6 Hz), 7,38-7,34 (m, 3H), 6.73 x (t, 1H, J=7.4 Hz), 5,88 of 5.84 (m, 3H), from 5.29 (t, 1H, J=5.3 Hz), 4,74 (s, 2H), 4,08 (d, 2H, J=5.3 Hz), 2,50 (s, 3H).

ESIMC m/z: 380 (M+H).

Compound 1j-3-58-2:

3-((3-(Methylaminomethyl)aminophenylamino)methyl)-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-2, except that the compound 1h-358 for was used instead of compound 1h-1-3.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 9,40 (s, 1H), 7,95 (d, 1H, J=8.7 Hz), 7,50 (d, 1H, J=2.5 Hz), 7,38-7,35 (m, 3H), 7,11 (kV, 1H, J=4.9 Hz), 6,98 (5, 1H, J=7.9 Hz), 6.48 in-6.42 per (m, 2H), 6,33 (d, 1H, J=7,1 Hz), 5,71 (d, 1H, J=4,5 Hz), 4,12 (d, 2H, J=4,8 Hz), of 2.51 (s, 3H), of 2.45 (d, 3H, J=4,8 Hz).

ESIMC m/z: 473 (M+H).

Compound 1E-0-NAc:

N-(7-Hydroxy-4-methyl-2-oxo-2H-1-benzopyran-3-yl)ndimethylacetamide

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1E-0-4, except that the ethyl ester of 2-acetylamino-3-oxomalonate (which is known in the literature) was used instead of compound 1C-2.

1H-NMR (270 MHz, DMSO-d6δ (ppm): 10,52 (s, 1H), 9,39 (s, 1H), 7,63 (d, 1H, J=8.6 Hz), at 6.84 (DD, 1H, J=8,5 and 2.2 Hz), 6.73 x (d, 1H, J=2.3 Hz), of 2.21 (s, 3H), 2,03 (s, 3H).

ESIMC m/z: 234 (M+H).

Compound 1E-0-NN2:

7-Hydroxy-4-methyl-2-oxo-2H-1-benzopyran-3-ilmoni chloride

5-6 N solution of ISO-propanol hydrochloride (3.0 ml) was added to a solution of compound 1E-0-NAc (600 mg, 2.57 mmol) in THF (6.0 ml) and water (0.6 ml) and the mixture was stirred at 80°C during the day and night. Then the mixture was cooled to room temperature and concentrated under reduced pressure to 1/3 volume. Precipitated precipitated solid was filtered to obtain specified in the title compound (510 mg, 87%) as a dull-orange solid.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 7,41 (d, 1H, J=8.7 Hz), 6,78 (DD, 1H, J=8,7, 2,5 Hz), 6,69 (d, 1H, J=2.3 Hz), 5,69 (users, 3H), 2,19 (s, 3H).

ESIMC m/z: 192 (M-HCl+H).

Compound 1E-0-60:

N-(7-Hydroxy-4-methyl-2-oxo-2H-1-benzopyran-3-yl)-2-nitrobenzenesulfonamide

Pyridine (of 0.18 ml of 2.20 mmol) and o-nitrobenzenesulfonamide (487 mg, of 2.20 mmol) was added to a solution of compound 1E-0-NH2(250 mg, 1.10 mmol) in THF (5.0 ml) and the mixture was stirred at room temperature during the day and night. Then to the reaction mixture was added water, extraction was performed with ethyl acetate and the organic extract was washed with water and saturated salt solution. After wysu the air traffic management over magnesium sulfate, it was concentrated under reduced pressure to get crude product, which then was purified column chromatography to obtain specified in the title compound (268 mg, 65%) as a yellow solid.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 10,66 (s, 1H), 9,86 (s, 1H), 8,04 (m, 1H), 7,94-7,83 (m, 3H), to 7.67 (d, 1H, J=8.7 Hz), 6,86 (DD, 1H, J=8,8, 2.4 Hz), 6,70 (d, 1H, J=2,8 Hz), of 2.38 (s, 3H).

ESIMC m/z: 377 (M+H).

Compound 1g-1-60:

3-(2-Nitrobenzenesulfonamide)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1g-1-5, except that the compound 1E-0-60 was used instead of compound 1E-0-5.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): to 10.09 (s, 1H), with 8.05 (m, 1H), 7,86-7,80 (m, 4H), 7,26-7,20 (m, 2H), 3,06 (s, 3H), of 2.93 (s, 3H), 2,43 (s, 3H).

ESIMC m/z: 448 (M+H).

Compound 1h-1-60:

3-(2-Aminobenzenesulfonamide)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 4A-0-4, except that the compound 1g-1-60 was used instead of compound 1E-0-4.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 7,78 (d, 1H, J=8:7 Hz), was 7.36 (d, 1H, J=8,4 Hz), 7,27-7,16 (m, 3H), 6,77 (d, 1H, J=8,4 Hz), of 6.52 (t, 1H, J=7.5 Hz), 3,06 (s, 3H), of 2.93 (s, 3H), 2,32 (s, 3H).

ESIMCm/z: 418 (M+H).

Compound 1j-1-60-2:

3-(2-Methylaminomethyl)aminobenzenesulfonamide)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-5-2, except that the compound 1h-1-60 was used instead of compound 1h-1-5.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 10,18 (s, 1H), 8,99 (s, 1H), 7,79 (m, 2H), a 7.62 (d, 1H, J=8.7 Hz), 7,60-6,55 (m, 2H), 7.23 percent-to 7.15 (m, 2H), was 7.08 (m, 1H), 3,06 (s, 3H), of 2.93 (s, 3H), 2,47 (d, 3H, J=4,8 Hz), 2.40 a (s, 3H).

ESIMC m/z: 511 (M+H).

Compound 5d-0-CO2N:

7-Hydroxy-4-methyl-2-oxo-2H-1-benzopyran-3-carboxylic acid

Pyridine (0.1 ml) and 1 N aqueous sodium hydroxide solution (20 ml) was added to 7-hydroxy-4-methyl-3-carbonitrile-2-oxo-2H-1-benzopyran (1.0 g, equal to 4.97 mmol) and the mixture was stirred at room temperature during the day and night. To the reaction mixture were added water and 6 N aqueous solution of hydrochloric acid (to pH 2) and the precipitation was filtered. Then it was washed with methanol to obtain specified in the title compound (577 mg, 53%).

1H-NMR (270 MHz, DMSO-d6) δ (ppm): a 10.74 (s, 1H), 7,72 (d, 1H, J=8.6 Hz), 6,86 (d, 1H, J=8.6 Hz), 6.75 in (s, 1H), 2,41 (s, 3H).

ESIMC m/z: 221 (M+H).

Compound 5d-0-R:

(3-Acetylaminophenol)amide 7-hydroxy-4-methyl--oxo-2H-1-benzopyranyl-3-carboxylic acid

HOBt (221 mg, of 1.64 mmol) and WSC (313 mg, of 1.64 mmol) was added to a solution of compound 5d-0-CO2H (300 mg, about 1.36 mmol) in DMF (10 ml) and the mixture was stirred at room temperature for 30 minutes Then the reaction mixture was added 3-aminoacetate (225 mg, 1.50 mmol) and stirred at room temperature for 1.5 hours Then the reaction mixture was added water, and extraction was performed with ethyl acetate. The organic extract was washed with saturated salt solution and dried over magnesium sulfate and then concentrated under reduced pressure to obtain specified in the title compound (217 mg, 45%) as a pale yellow solid.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): of 10.73 (s, 1H), 10,45 (s, 1H), 9,99 (s, 1H), 7,98 (s, 1H), 7,73 (d, 1H, J=8.7 Hz), 7,34 (m, 2H), 7,24 (t, 1H, J=7.8 Hz), to 6.88 (m, 2H), 6,77 (d, 1H, J=2.3 Hz), 2,39 (s, 3H), 2,04 (s, 3H).

ESIMC m/z: 353 (M+H).

Compound 5d-0-56:

(3-AMINOPHENYL)amide 7-hydroxy-4-methyl-2-oxo-2H-1-benzopyranyl-3-carboxylic acid

Concentrated sulfuric acid (0.3 ml) was added to a suspension of compound 5d-0-R (200 mg, or 0.57 mmol) in ethanol (5.0 ml), THF (3.0 ml) and water (0.5 ml)and the mixture was stirred while boiling under reflux for 4 hours After cooling to room temperature was added a saturated sodium bicarbonate solution and extraction was performed di is loretana. The organic extract was dried over magnesium sulfate and then concentrated to obtain specified in the title compound (143 mg, 81%) as a pale yellow solid.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 10,70 (s, 1H), 10,11 (s, 1H), 7,72 (d, 1H, J=8.7 Hz), 7,01 (s, 1H), 6,95 (t, 1H, J=7.9 Hz), 6,86 (DD, 1H, J=8,4, and 2.1 Hz), 6,77 (d, 1H, J=1.6 Hz), of 6.71 (d, 1H, J=7,6 Hz), 6.30-in (d, 1H, J=5.8 Hz), 5,13 (users, 2H), of 2.38 (s, 3H).

ESIMC m/z: 311 (M+H).

Compound 1h-1-56:

3-(3-Aminophenylamino)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1g-1-5, except that compound 5d-0-56 was used instead of compound 1E-0-5.

1H-NMR (270 MHz, CD3OD) δ (ppm): 8,13 (d, 1H, J=1.8 Hz), 7,92 (d, 1H, J=8.6 Hz), 7,49 (m, 2H), 7,24 m, 2H), 7,14 (dt, 1H, J=5,6, 1.3 Hz)and 3.15 (s, 3H), to 3.02 (s, 3H), by 2.55 (s, 3H).

ESIMC m/z: 382 (M+H).

Compound 1j-1-56-2:

3-(3-Methylaminomethyl)aminophenylamino)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-2, except that the compound 1h-1-56 used instead of compound 1h-1-3.

1H-NMR (270 MHz, DMSO-d6 ) δ (ppm): 10,52 (s, 1H), 9,74 (s, 1H), 7,92 (d, 1H, J=8.6 Hz), 7,47-7,42 (m, 2H), 7,34 (m, 1H), 7,30-7,22 (m, 3H), 6,97 (d, 1H, J=7.4 Hz), is 3.08 (s, 3H), 2.95 and (s, 3H), 2,47 (d, 3H, J=4.0 Hz), a 2.45 (s, 3H).

ESIMC m/z: 475 (M+H).

2-Hydroxy-4-(pyrimidine-2-yloxy)benzoic acid

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-2-4, except that 2,4-dihydroxybenzoic acid was used instead of compound 1E-0-4.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 8,69 (d, 2H, J=4,8 Hz), the 7.85 (d, 1H, J=8.6 Hz), 7,33 (t, 1H, J=4,8 Hz), for 6.81 (d, 1H, J=2.3 Hz), 6,77 (DD, 1H, J=8,6, 2,3 Hz).

ESIMC m/z: 233 (M+H).

3-amino-ethyl-2-forfinally

The solution hexamethyltetraline (595 mg, 4,24 mmol) in chloroform (4.0 ml) was boiled under reflux and then was added a solution of N-(3-methyl bromide-2-forfinal)ndimethylacetamide (950 mg, 3,86 mmol) in chloroform (8.0 ml) for 40 minutes Then the reaction mixture is boiled under reflux for 1 h and after cooling to room temperature the white precipitate was filtered and washed with chloroform. The white precipitate was added methanol (24 ml) and concentrated hydrochloric acid (3.0 ml) and the mixture was stirred at room temperature for 30 minutes After cooling to 0°C. the reaction mixture was podslushivaet with 6 N aqueous solution of sodium hydroxide (16,5 ml Then it was extracted with dichloromethane and the organic extract was washed with saturated salt solution and dried over magnesium sulfate, and again washed with a saturated solution of salt. After drying over magnesium sulfate dried extract was concentrated under reduced pressure to get crude product which was then purified column chromatography to obtain specified in the title compound (337 mg, 48%) as a brown solid.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 6,79 (t, 1H, J=7,6 Hz), 6,52 is 6.67 (m, 2H), to 4.98 (s, 2H).

ESIMC m/z 141 (M+H).

Compound 1h-1-73:

3-(Amino-2-terbisil)-7-(pyrimidine-2-yloxy)benzo[e][1,3]oxazin-2,4-dione

The triethylamine (0,180 ml, 1,29 mmol) was added to a mixture of 2-hydroxy-4-(pyrimidine-2-yloxy)benzoic acid (100 mg, 0,431 mmol) and chloroform (5.0 ml) at room temperature. The dark brown solution was cooled to 4°C and to it was added methylchloroform (0,073 ml, 0,945 mmol). Received light purple solution was stirred at room temperature for 2.5 h and then concentrated under reduced pressure. Then it was again dissolved in chloroform (5.0 ml) and to it was added a solution of triethylamine (0,120 ml, 0,861 mmol) and 3-amino-ethyl-2-ftorhinolona (60,0 mg, 0,428 mmol) in chloroform (1.0 ml). The resulting mixture was stirred at room temperature for 64 hours Then to the reaction mixture were added water and extraction was performed with ethyl acetate. The organic extract was washed with saturated salt solution and dried over magnesium sulfate and then again washed with a saturated solution of salt. After drying over magnesium sulfate, it was concentrated under reduced pressure to get crude product which was then purified column chromatography to obtain specified in the connection header (from 25.8 mg, 16%) as a white solid.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 8,72 (d, 2H, J=4,8 Hz), with 8.05 (d, 1H, J=8.7 Hz), 7,47 (d, 1H, J=2.1 Hz), 7,38 (t, 1H, J=4,8 Hz), 7,35 (DD, 1H, J=8,7, and 2.1 Hz), 6,78 (t, 1H, J=7.8 Hz), to 6.67 (m, 1H), 6,45 (m, 1H), further 5.15 (s, 2H)that is 5.06 (s, 2H).

ESIMC m/z: 381 (M+H).

Compound 1j-1-73-2:

3-(3-(Methylaminomethyl)-2-terbisil)-7-(pyrimidine-2-yloxy)benzo[e][1,3]oxazin-2,4-dione

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-2, except that 3-(3-amino-2-terbisil)-7-(pyrimidine-2-yloxy)benzo[e][1,3]oxazin-2,4-dione (compound 1h-1-73) was used instead of compound 1h-1-3.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 9,44 (s, 1H), 8,71 (d, 2H, J=4,8 Hz), with 8.05 (d, 1H, J=8.7 Hz), of 7.48 (d, 1H, J=2.2 Hz), 7,38 (t, 1H, J=4,8 Hz), 7.29 trend was 7.36 (m, 2H), 7,25 (userc, 1H, J=5,1 Hz), to 7.15 (m, 1H), 7,07 (t, 1H, J=7.9 Hz), 5,11 (s, 2H).

One of the methyl peaks overlap with Pico is DMSO.

ESIMC m/z: 474 (M+H).

2-(3-Methylbenzo[b]thiophene-6-yloxy)pyrimidine

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-2-4, except that 4-gidroksiflavona acid was used instead of compound 1E-0-4.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 8,64 (d, 2H, J=4.5 Hz), the 7.85 (d, 1H, J=2.1 Hz), 7,79 (d, 1H, J=8.7 Hz), 7,39 (d, 1H, J=1.1 Hz), 7,27 (t, 1H, J=4,8 Hz), 7,27 (DD, 1H, J=8,7, and 2.1 Hz), 2,42 (s, 3H).

ESIMC m/z: 243 (M+H).

Compound 1g-2-74:

2-(2-(2-Fluoro-3-nitrobenzyl)-3-methylbenzo[b]thiophene-6-yloxy)pyrimidine

1-methyl bromide-2-fluoro-3-nitrobenzene (120 mg, 0,513 mmol) and zinc chloride (71 mg, 0,520 mmol) was added to a solution of 2-(3-methylbenzo[b]thiophene-6-yloxy)pyrimidine (114 mg, 0,470 mmol) in dichloromethane (1.0 ml) and the mixture is boiled under reflux for 17,5 hours After cooling to room temperature, to the mixture was added 1-methyl bromide-2-fluoro-3-nitrobenzene (120 mg, 0,513 mmol) and zinc chloride (71 mg, 0,520 mmol) and the mixture is boiled under reflux for 23 hours Then the reaction mixture was concentrated under reduced pressure and was purified column chromatography to obtain specified in the connection header (67.5 mg, 36%) as a white solid.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 8,63 (d, 2H, J=4,8 Hz), with 8.05 (m, 1H), 7,70-7,80 (m, 3H),7,41 (m, 1H), 7,26 (t, 1H, J=4,8 Hz), 7,24 (DD, 1H, J=8,5, and 2.1 Hz), and 4.40 (s, 2H), 2,41 (s, 3H).

ESIMC m/z: 366 (M+H).

Compound 1h-2-74:

2-Fluoro-3-(3-methyl-6-(pyrimidine-2-yloxy)benzo[b]thiophene-2-ylmethyl)phenylamine

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1h-1-5, except that 2-(2-(2-fluoro-3-nitrobenzyl)-3-methylbenzo[b]thiophene-6-yloxy)pyrimidine (compound 1g-2-74) was used instead of compound 1E-1-5.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): to 8.62 (d, 2H, J=4,8 Hz), 7,72 (m, 2H), 7,26 (t, 1H, J=4,8 Hz), 7,33 (DD, 1H, J=8,7, and 2.1 Hz), 6,79 (t, 1H, J=7.9 Hz), is 6.61 (m, 1H), gold 6.43 (m, 1H), 5,10 (s, 2H), 4,14 (s, 2H), 2,39 (s, 3H).

ESIMC m/z: 366 (M+H).

Compound 1j-2-74-2:

[2-Fluoro-3-(3-methyl-6-(pyrimidine-2-yloxy)benzo[b]thiophene-6-ylmethyl)phenyl]methylaminoethanol

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-2, except that 2-fluoro-3-(3-methyl-6-(pyrimidine-2-yloxy)benzo[b]thiophene-2-ylmethyl)phenylamine (compound 1h-2-74) was used instead of compound 1h-1-3.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 9,40 (s, 1H), to 8.62 (d, 2H, J=4,8 Hz), 7,72 (m, 2H), 7,33 (TD, 1H, J=7,8, 2.0 Hz), 7.18 in-7,28 (m, 4H), 7,00-to 7.15 (m, 2H), 4,25 (s, 2H), 2,39 (s, 3H).

One of the methyl peaks overlap with DMSO peak.

ESIMC m/z: 459 (M+H).

4-(Pyrimidine-2-yloxy)phthalic acid is that

Specified in the title compound was synthesized under the same conditions described in example obtaining compounds 1g-2-4, except that 4-gidroksiflavona acid was used instead of compound 1E-0-4.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 8,68 (d, 2H, J=4,8 Hz), 7,78 (d, 1H, J=8,3 Hz), 7,39-7,46 (m, 2H), 7,32 (t, 1H, J=4,8 Hz).

ESIMC m/z: 261 (M+H).

Compound 1h-2-75:

2-(3-Amino-2-terbisil)-5-(pyrimidine-2-yloxy)isoindole-1,3-dione

3-Aminomethyl-2-forfinally (50,8 mg, 0,362 mmol) and imidazole (26,0 mg, 0,382 mmol) was added to a solution of 4-(pyrimidine-2-yloxy)phthalic acid (94,1 mg, 0,362 mmol) in DMF (2.0 ml) and the mixture was stirred in the microwave at 300 W, 150°C for 5 min. Then the reaction mixture was added water, extraction was performed with ethyl acetate and the organic extract was washed with a saturated solution of salt. After drying over magnesium sulfate, it was concentrated under reduced pressure to get crude product which was then purified column chromatography to obtain specified in the connection header (13,4 mg, 10%) as a white solid.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 8,70 (d, 2H, J=4,8 Hz), of 7.97 (d, 1H, J=8,2 Hz), 7,80 (d, 1H, J=2.2 Hz), 7,69 (DD, 1H, J=8,2, 2.2 Hz), was 7.36 (t, 1H, J=4,8 Hz), 6,79 (t, 1H, J=7.9 Hz), 6,66 (m, 1H), 6,40 (m, 1H), 5,17 (s, 2H), and 4.75 (s, 2H).

ESIMC m/z: 365 (M+H).

Compound 1j-2-75-2:

2-(3-(Methylaminomethyl)-2-terbisil)-5-(pyrimidine-2-yloxy)isoindole-1,3-dione

Specified in the title compound was synthesized under the same conditions described in example obtain compound 1j-1-3-2, except that 2-(3-amino-2-terbisil)-5-(pyrimidine-2-yloxy)isoindole-1,3-dione (compound 1h-2-75) was used instead of compound 1h-1-3.

1H-NMR (270 MHz, DMSO-d6) δ (ppm): 8,70 (d, 2H, J=4,8 Hz), 7,98 (d, 1H, J=7.9 Hz), 7,81 (d, 1H, J=2.0 Hz), 7,69 (DD, 1H, J=7,9, 2.0 Hz), was 7.36 (m, 2H), 7,24 (userc, 1H, J=5,1 Hz), to 7.09 (m, 2H), 4,82 (s, 2H), 3,17 (d, 1H, J=5,1 Hz).

ESIMC m/z: 458 (M+H).

Ethyl ester (3-acetylbenzenesulfonyl)acetic acid

Ethanol was added at 0°C. to a solution of chlorosulfonylisocyanate (1.0 g, 5.7 mmol) in diethyl ether (6 ml) and the mixture was stirred for 2 h and the solvent drove away. To the reaction mixture were added N-(3-AMINOPHENYL)ndimethylacetamide (0,89 g), triethylamine (1.2 ml) and tetrahydrofuran (10 ml) and the resulting mixture was stirred at room temperature overnight. Then it was purified by chromatography on silica gel (mixture of methylene chloride:methanol = 50:1) to obtain specified in the connection header (0,77 g, 46%).

1H-NMR (Bruker (ARX-300), 300 MHz, CDCl3) δ (ppm): 7,49 (1H, user. C), 7,44 (1H, user. C), 7,31 (1H, t, J=8.0 Hz), 7,19 (1H, user. C)7,06 (1H, d, J=8.0 Hz), 6,94 (1H, user. C), 4,28 (2H, to the, J=7,2 Hz), of 3.95 (2H, s)to 2.18 (3H, s)of 1.32 (3H, t, J=7.2 Hz).

MS (ESI+) m/z: 301,11 (M+1).

Compound 5d-0-61P:

4-Methyl-3-(3-(acetylamino)phenylenesulfonyl)-7-hydroxy-2-oxo-2H-1-benzopyran

Ethyl ester (3-acetylbenzenesulfonyl)acetic acid (280 mg, of 0.93 mmol), 2,4-dihydroxybenzaldehyde (516 mg) and piperidine (10 mg) was added to 9 ml of ethanol and the mixture is boiled under reflux during the night. Then the mixture was purified by chromatography on silica gel (mixture of methylene chloride:methanol = 30:1) to obtain the specified title compound (304 mg, 87%).

1H-NMR (Bruker (ARX-300), 300 MHz, DMSO-d6) δ (ppm): 11,2 (1H, s)to 10.4 (1H, s)of 9.89 (1H, user. C)8,71 (1H, s), 7,78 (1H, d, J=8,8 Hz), 7,45 (1H, user. C), 7,22 (1H, d, J=8.0 Hz), 7,11 (1H, t, J=8.0 Hz), 6,86 (1H, DD, J=2.3 Hz, J=8.0 Hz), to 6.80 (1H, d, J=8.0 Hz), 6,74 (1H, s)to 1.98 (3H, s).

MS (ESI+) m/z: 374,80 (M+1).

Compound 5d-0-61:

4-Methyl-3-(3-aminobenzenesulphonyl)-7-hydroxy-2-oxo-2H-1-benzopyran

Specified in the title compound was obtained using compound 5d-0-R and 4 EQ methanesulfonic acid by boiling under reflux in a solvent mixture of ethanol/water.

1H-NMR (Bruker (ARX-300), 300 MHz, DMSO-d6) δ (ppm): 11,2 (1H, user. C), and 10.0 (1H, s), 8,67 (1H, s), 7,79 (1H, d, J=8,8 Hz)6,86 (1H, DD, J=2.3 Hz, J=8.0 Hz), PC 6.82 (1H, t, J=8.0 Hz), 6,74 (1H, s), 6,36 (1H, m), 6,30 (1H, d, J=8.0 Hz), of 6.20 (1H, d, J=8.0 Hz), 5,15 (2H, user. C).

MS (ESI+) m/z: 332,92 (M+1).

Examples test

Example test 1: evaluation of inhibitory activity against cell proliferation

Inhibitory activity of the compounds and salts in relation to the proliferation of cells whose values are shown in tables 1-1, 1-2 and table 2, was determined as shown below using cell lines of malignant tumors of the colon of a person NST (American type culture collection, VA, USA). 2000-3000 cells of a malignant tumor of the colon of a person NST per well were placed in 96-well culture tablet, contributed a predetermined concentration of the test compounds (0,00038 μm, 0,00076 μm, 0,0015 μm, 0,0031 μm, 0,0061 μm, a 0.012 μm, 0,024 μm, 0,049 μm, 0,098 μm, of € 0.195 μm, of 0.39 μm to 0.78 μm and 1.56 μm, 3,13 μm, and 6.25 μm, 12.5 μm, 25 μm or 50 μm) and the mixture is incubated at 37°C in an atmosphere of 5% CO2within 4 days. On the 4th day of incubation in the wells was made solution kit-8 for counting cells (Dojindo Laboratories), was determined by absorption (detection at a wavelength of 450 nm; reference wavelength: 615 nm), following the Protocol supplied with the kit, and expected 50% proliferation inhibitory concentration (IC50). The results are shown in tables 1-1, 1-2 and table 2.

Sample test 2: definition of AUC values

The values of AUC (area under the curve concentration-time) for compounds and salts are given in table the CE 2 (compound 1j-2-16-2 is Na salt; all others were in the free form) was determined with the introduction of the test compound to the animal and determine its concentration in the blood plasma. As experimental animals used BALB/c mice (nu/nu) (ages 4 to 6 weeks), obtained from Japan Charles River Laboratories, after 1 week of exposure. For the test compounds other than compound 1, 5 mg/ml solution of the compound was injected at the rate of 0.2 ml/10 g body weight (dose of test compound: 100 mg/kg body weight). In respect of compounds 1, 10 mg/ml solution of the compound was injected at the rate of 0.2 ml/10 g body weight (dose tested compounds: 200 mg/kg body weight). Solution connection was forcibly injected into mice using a sonde for oral feeding. The blood was collected from the retro-bulbar plexus eyes after 15 min, 2 h, 7 h and 24 h after injection of a solution of the compound in a test tube to determine the hematocrit of heparin. As a stabilizer for selected blood was added paraoxon (final concentration: 1 mm), the mixture was centrifuged at 10000 rpm for 3 min and separated blood plasma. The blood plasma before analysis were stored in a freezer at -80°C. Determination was carried out as follows. 100 µl of distilled water with the internal standard (structural analogue, concentration brought depending on the compound) was added to 5 µl of blood plasma and then hotfilefree solid-phase extraction using Oasis HLB µElution Plate (Waters) and were analyzed by LC/MS/MS. Concentration in plasma was determined by a calibration curve constructed on the basis of the ratio of standard connections to the internal standard in the test plasma of mice. AUC values were calculated according to the concentration of drug in plasma trapezoidal method using Microsoft Excel 2003 software (Microsoft). The results are shown in table 2.

Compounds or salts of the present invention are shown in tables 1-1, 1-2 and table 2 below, the compounds listed in the description. "Compound 1" means the compound from example 20-44 described in international publication WO 2002/008217, i.e. the compound of formula (A)below. "Connection 2" means the compound from example 2, described in international publication WO 2002/008217, i.e. the compound of formula (C)below (2-oxo-2H-3-benzyl-4-methyl-6-chloro-1-benzopyran-7-silt ether dimethylcarbinol acid).

Chemical formula 177

Chemical formula 178

Table 1-1
ConnectionIC50(µm)
1j-1-4-10,0176
1j-1-4-2 0,0093
1j-1-4-2F0,0106
1j-1-5-10,0083
1j-1-5-20,0029
1j-1-3-20,0041
1j-1-2-30,0120
1j-1-3-2F0,0195
1j-1-7-10,0114
1j-1-7-20,0079
1j-1-8-20,0217
1j-1-9-20,0242
1j-1-21-20,0230
1j-1-23-20,0360
1o-1-3-20,0210
1o-1-3-30,0160

Table 1-2
ConnectionIC50(µm)
1j-1-10-20,0319
1j-1-11-20,0183
0,0064
1j-2-17-20,0211
1j-2-18-20,0059
1j-2-19-20,0178
1j-2-19-me0,0084
1j-3-4-10,0225
1j-3-4-20,0109
1j-3-20-20,0089
1j-3-12-20,0122
1j-3-19-20,0015
1j-3-44-20,0129
Connection 10,1600
Connection 2above 1.3000

1j-2-4-2
Table 2
ConnectionAUS (µm×h)IC50(µm)
1j-1-13-2313-60,2711
1j-2-4-18110,1496
4250,0447
1j-2-4-2F3170,1654
1j-2-5-23440,0751
1j-2-12-22520,2816
1j-2-16-23203 (*)0,0408
1j-3-1-2199,30,1636
1j-3-8-2148,90,0968
1o-3-4-23670,3253
Connection 197,60,1600
(*)Used Na salt

As follows from the data of tables 1-1, 1-2 and table 2, the compound or salt of the present invention had a significantly lower IC50 value compared to the comparable standard connections or had low IC50 value and a higher AUC compared compared with standard compounds. Based on this we can assume that the connection is giving or salt of the present invention has a significantly higher antitumor activity compared with the comparable standard connections or that it has a sufficiently high antitumor activity is equal to the compared standard compounds, and has a higher system availability than compared with standard connections.

The results of test examples 1 and 2 showed that the compound or its pharmaceutically acceptable salt according to the present invention is effective as a drug for the treatment of cell proliferative disorders, in particular cancer.

Industrial applicability

The compound or its pharmaceutically acceptable salt, pharmaceutical composition and a pharmaceutical agent for the treatment of cell proliferative disorders of the present invention can be used for the treatment of cell proliferative disorders, in particular cancer.

1. The compound of General formula (11)below, or its pharmaceutically acceptable salt:
Chemical formula 1

in which:
G1, G2, G3and G8each independently represents-N=, -CR1= or-C(-G9X)=;
one of the G1, G2, G3and G8is-S(-G9X)=;
X represents C1-6alkyl (where C1-6the alkyl may be optionally substituted by a group selected from halogen atom, hydroxy, cyano, and-NR56R57), aryl, heterocycle where the heterocycle means 5-9-membered, saturated or not assistnow cyclic group, including one or more heteroatoms selected from nitrogen atoms, oxygen and sulfur, and may be a monocycle or a condensed cycle, and may be optionally substituted by a halogen atom, a C1-6the alkyl, C1-6alkoxy, R33R34NCS-, R3R4NCO-);
G9represents a simple bond, oxygen atom, sulfur atom;
cycle G6represents a divalent aryl group or a divalent pyridyloxy group (where divalently Peregrina group may be optionally substituted by a halogen atom);
A represents a group of General formula (2)below, or a group of the General formula (3)below:
Chemical formula 2

Chemical formula 3

G4represents an oxygen atom or a sulfur atom;
G5represents an oxygen atom or a sulfur atom;
G7represents an oxygen atom, -CR42R43-, -CONR44-, -NR44CO-, -NR45-, CR42R43NR45-, -S-, -NR44S(=O)2-;
R1represents a hydrogen atom, halogen atom, cyano, C1-6alkyl (where C1-6the alkyl may be optionally substituted by halogen atom), carbarnoyl or2-7quinil (where C2-7quinil may be optionally substituted C1-4the acyl);
when G2or G3the submitted who-CR 1=, G8is-C(-G9-X)=, and X represents R3R4NCO-, R33R34NCS-; when G8is-CR1=, G3represents-C(-G9X)=, and X represents R3R4NCO-, or R33R34NCS-;
when G1or G8represents-CR1=, G2is-C(-G9-X)=, and X represents R3R4NCO-, or R33R34NCS-; or when G2is-CR1=, G1represents-C(-G9X)=, and X represents R3R4NCO-, or R33R34NS-;
R1can form a simple bond or-CH2- R4or R34;
R2represents hydroxy or C1-6alkyl (where C1-6the alkyl may be optionally substituted by a group selected from halogen atom, hydroxy, C1-6alkoxy, formyl and-CO2R50);
R3, R4, R9and R10each independently represents a hydrogen atom, a C3-8cycloalkyl or C1-6alkyl (where C1-6the alkyl may be optionally substituted by a group selected from cyano, halogen atom, hydroxy, C1-6alkoxy, -NR13R14and CONR28R29);
R6and R7each independently represents a hydrogen atom, a C1-6alkoxy, C3-8cycloalkyl or C1-6alkyl (where C1-6the alkyl may be optionally substituted group selected Asciano, of halogen atom, hydroxy, C1-6alkoxy, -NR13R14and CONR28R29);
R33and R34each independently represents a hydrogen atom, a C1-6alkyl;
the combination of R3and R4may form together with the nitrogen atom to which they relate, 5-6-membered heterocyclic group containing at least one nitrogen atom (where 5-6-membered heterocyclic group containing at least one nitrogen atom, means a saturated or unsaturated heterocyclic group containing 5 to 6 atoms in the ring which optionally one or more nitrogen atoms may contain one or more heteroatoms selected from oxygen atom and sulfur (where 5-6-membered heterocyclic group may be optionally condensed with benzene ring); and which may be optional substituted by a halogen atom or C1-6by alkyl;
the combination of R6and R7may form together with the nitrogen atom to which they relate, 5-6-membered heterocyclic group containing at least one nitrogen atom (where 5-6-membered heterocyclic group containing at least one nitrogen atom, means a saturated or unsaturated heterocyclic group containing 5 to 6 atoms in the ring which optionally one or more nitrogen atoms may contain one or more gateroad the MOU, selected from oxygen atom and sulfur (where 5-6-membered heterocyclic group may be optionally condensed with benzene ring); and which may be optionally substituted by a halogen atom, a C1-6the alkyl or oxopropoxy;
R45represents a hydrogen atom;
R13and R14each independently represents a hydrogen atom, a C1-6alkyl, or-COR32;
R56and R57each independently represents a hydrogen atom or a C1-6alkyl, and R5, R8,
R28, R29, R32, R42, R43, R44and R50each independently represents a hydrogen atom or a C1-6alkyl.

2. The compound or its pharmaceutically acceptable salt according to claim 1, where the compound of General formula (11) represents the compound of General formula (1)below:
Chemical formula 1

in which:
X represents heteroaryl or R3R4JI-;
Y1and Y2each independently represents-N= or-CR11=;
Y3and Y4may be the same or different and each represents-CR12=;
And is a group of the General formula (2)below, or a group of the General formula (3)below:
Chemical formula 2

Chemical formula 3

R1is the volume of hydrogen, halogen atom, cyano, C1-6alkyl, carbarnoyl, or
C2-7quinil (where C2-7quinil may be optionally substituted C1-4the acyl);
R2represents C1-6alkyl, optionally substituted by a halogen atom;
R3, R4, R9and R10each independently represents a hydrogen atom, a C3-8cycloalkyl or1-6alkyl (where C1-6the alkyl may be optionally substituted by a group selected from cyano, halogen atom, hydroxy, C1-6alkoxy, -NR13R14);
R6and R7each independently represents a hydrogen atom, a C1-6alkoxy, C3-8cycloalkyl or C1-6alkyl (where C1-6the alkyl may be optionally substituted by a group selected from cyano, halogen atom, hydroxy, C1-6alkoxy, -NR13R14);
the combination of R3and R4and the combination of R6and R7may form together with the nitrogen atom to which they relate, 5-6-membered heterocyclic group containing at least one nitrogen atom (where 5-6-membered heterocyclic group containing at least one nitrogen atom, means a saturated or unsaturated heterocyclic group containing 5 to 6 atoms in the ring which optionally one or more nitrogen atoms may contain one or more heteroatoms selected from oxygen atom and sulfur(where 5-6-membered heterocyclic group may be optionally condensed with benzene ring); and which may be optionally substituted by a halogen atom, and C1-6by alkyl);
R5, R8, R13and R14each independently represents a hydrogen atom or a C1-6alkyl;
R11represents a hydrogen atom, halogen atom or C1-6alkyl when Y1or Y2are not-N=; and
R11represents a hydrogen atom or a halogen atom when Y1or Y2is-N=; and
R12represents a hydrogen atom or a halogen atom.

3. The compound or its pharmaceutically acceptable salt according to claim 2, in which R1represents a hydrogen atom, halogen atom or C1-6alkyl.

4. The compound or its pharmaceutically acceptable salt according to claim 2 or 3, in which R5or R8represents a hydrogen atom.

5. The compound or its pharmaceutically acceptable salt according to claim 2, in which R3, R4, R6, R7, R9or R10each independently represents a hydrogen atom or a C1-6alkyl.

6. The compound or its pharmaceutically acceptable salt according to claim 2, in which X is thiazol-2-yl, pyrimidine-2-yl, 2-pyridyl or R3R4NCO- (where R3and R4have the meanings defined above).

7. The compound or its pharmaceutically acceptable salt according to claim 6, in which both R3and R4are methyl group.

8. The compound or pharmaceutical the ski acceptable salt according to claim 2, in which R2represents C1-6alkyl, optionally substituted by a fluorine atom.

9. The compound or its pharmaceutically acceptable salt according to claim 8, in which R2represents-CH3, -CH2F or-CH2CH3.

10. The compound or its pharmaceutically acceptable salt according to claim 2, which is:
3-{3-(aminosulfonyl)aminobenzyl}-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-{3-(aminosulfonyl)aminobenzyl}-6-fluoro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-{3-(aminosulfonyl)aminobenzyl}-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-(3-aminosulfonyl-2-terbisil)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-{2-fluoro-3-(aminosulfonyl)aminobenzyl}-6-fluoro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-{3-(aminosulfonyl)aminobenzyl}-6-iodine-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-{3-(aminosulfonyl)aminobenzyl}-6-methyl-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-{3-(aminosulfonyl)aminobenzyl}-6-cyano-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-{3-(aminosulfonyl)aminobenzyl}-4-vermeil-2-oxo-2H-1-benzopyran-7-silt aired dimethylcarbamyl the OIC acid,
3-{3-(aminosulfonyl)aminobenzyl}-6-fluoro-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-{3-(aminosulfonyl)aminobenzyl}-6-chloro-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-(3-aminosulfonyl-2-terbisil)-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-{2-fluoro-3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-6-chloro-2-oxo-2H-1-benzopyran,
3-{2-fluoro-3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-6-methyl-2-oxo-2H-1-benzopyran,
3-{2-chloro-3-(aminosulfonyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,
4-methyl-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
6-fluoro-4-methyl-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-(3-(N-methylsulfonyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-(3-methylmonoethanolamine-2-terbisil)-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbamyl the howling acid,
6-iodine-4-methyl-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
6-methyl-4-methyl-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
6-cyano-4-methyl-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
4-methyl-3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
4-methyl-3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-6-fluoro-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
4-methyl-3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-6-chloro-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
4-methyl-3-{6-(methylaminomethyl)aminopyridine-2-ylmethyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
4-methyl-3-{6-(methylaminomethyl)aminopyridine-2-ylmethyl}-6-fluoro-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
4-methyl-3-{6-(methylaminomethyl)aminopyridine-2-ylmethyl}-6-chloro-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-(3-methylmonoethanolamine-2-terbisil)-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-(3-methylaminoanthraquinone)-4-vermeil-2-oxo-2H-1-benzopyran-7-silt epigenetically acid,
3-(3-methylaminoanthraquinone)-6-fluoro-4-vermeil-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
6-chloro-4-vermeil-3-{3-(methylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-6-fluoro-2-oxo-2H-1-benzopyran,
3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-vermeil-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-6-chloro-2-oxo-2H-1-benzopyran,
3-{3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-6-chloro-2-oxo-2H-1-benzopyran,
3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(thiazol-2-yloxy)-6-methyl-2-oxo-2H-1-benzopyran,
6-chloro-4-methyl-3-{3-(dimethylaminomethyl)aminobenzyl}-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-{2-fluoro-3-(dimethylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2 is-1-benzopyran,
3-(3-(N-(2-cyanoethyl)sulfamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-(3-(N-(2-hydroxyethyl)sulfamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-(3-(N-(2-methoxyethyl)sulfamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-(3-(N-(2-amino-ethyl)sulfamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-(3-(N-(N'-methyl-2-amino-ethyl)methylcarbamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid hydrochloride,
3-(3-(N-2,2,2-triftormetilfullerenov)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-(3-(N-methoxymethanol)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-(3-carbamoyltransferase)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
3-(3-methylcarbamoylmethyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-silt ether dimethylcarbinol acid,
2-{2-fluoro-3-[4-methyl-2-oxo-7-(pyrimidine-2-yloxy)-2H-1-benzopyran-3-ylmethyl]phenylsulfanyl}-N-methylacetamide,
3-(3-dimethylallyltranstransferase)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-and the new ether dimethylcarbinol acid,
2-{2-fluoro-3-[4-methyl-2-oxo-7-(thiazol-2-yloxy)-2H-1-benzopyran-3-ylmethyl]phenylsulfanyl}-N-methylacetamide,
3-{2-methyl-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(ethylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(isopropylaminocarbonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-fluoro-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(cyclopropanesulfonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-fluoro-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-chloro-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-ethyl-6-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(cyclopropanesulfonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(cyclopropanesulfonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzop the Russian Academy of Sciences,
3-{2-(methylaminomethyl)amino-3-chloropyridin-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-4-methyl-6-chloro-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(cyclopropanesulfonyl)amino-3-herperidin-4-ylmethyl}-4-methyl-6-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(methylaminomethyl)aminopyridine-4-ylmethyl}-4-methyl-6-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(methylaminomethyl)amino-3-chloropyridin-4-ylmethyl}-4-methyl-6-methyl-7-(thiazol-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(5-ftorpirimidinu-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(4-chloropyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(2,4-dimethoxypyrimidine-6-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(benzothiazol-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(5-bromothiazole-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(5-ftorpirimidinu-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(methylaminomethyl)amino-3-herperidin-4-metil}-4-methyl-7-(4-chloropyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(2,4-dimethoxypyrimidine-6-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(benzothiazol-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(5-bromothiazole-2-yloxy)-2-oxo-2H-1-benzopyran,
3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyrazin-2-yloxy)-2-oxo-2H-1-benzopyran and
3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyridine-2-yloxy)-2-oxo-2H-1-benzopyran.

11. The compound or its pharmaceutically acceptable salt according to claim 2, which is:
3-{2-fluoro-3-(methylaminomethyl)aminobenzyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran.

12. The compound or its pharmaceutically acceptable salt according to claim 2, which is:
3-{2-(methylaminomethyl)amino-3-herperidin-4-ylmethyl}-4-methyl-7-(pyrimidine-2-yloxy)-2-oxo-2H-1-benzopyran.

13. Pharmaceutical composition having inhibitory activity against the proliferation of cells containing the compound or its pharmaceutically acceptable salt according to one of claims 1 to 12, as the active ingredient.

14. Drug for the treatment of cell proliferative disorders, containing the compound or its pharmaceutically acceptable salt according to one of claims 1 to 12, ka is este active ingredient.

15. Drug for the treatment of cellular proliferative disorders in 14, where the cellular proliferative violation is cancer.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to a method for synthesis of 5-(4-oxo-2-thioxo-1,3,4,5-tetrahydro-2H-chromeno [2,3-d] pyrimidin-5-yl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione of formula

, which involves reaction of thiobarbituric acid with salicylic aldehyde in ethyl alcohol medium with molar ratio of reagents equal to 1:1 at temperature 70-80°C for 30 minutes.

EFFECT: novel method for synthesis of said compounds with high output, which can be used as a intermediate product for preparing medicinal agents for treating Alzheimer's disease.

1 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I)

or pharmaceutically acceptable salts thereof, in which: R1, R2, R3, R4, A and E are as described in the claim, and to pharmaceutical composition containing said compounds, and a method of treating and application in order to treat conditions mediated by antagonistic activity towards acid pump, such as gastrointestinal diseases, gastrooesophageal diseases, gastrooesophageal reflux disease (GERD), laryngopharyngeal reflux disease, peptic ulcers, gastric ulcers, duodenal ulcers, NSAID- induced ulcers, gastritis, Helicobacter pylori infection, dyspepsia, functional dyspepsia, Zollinger-Ellison syndrome, nonerosive reflux disease (NERD), viscerogenic pain, cancer, heartburn, nausea, oesophagitis, dysphagia, hypersalivation, disorders of the respiratory channel or asthma.

EFFECT: possibility of using compounds to treat different diseases.

9 cl, 1 tbl, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula [I-D1] or pharmaceutically acceptable salt thereof,

,

where each symbol is defined in the claim. The invention also relates to pharmaceutical compositions containing said compound and having HCV polymerase inhibiting activity.

EFFECT: disclosed compound exhibits anti-HCV activity, based on HCV polymerase inhibiting activity and is useful as an agent for preventing and treating hepatitis C.

32 cl, 497 tbl, 1129 ex

FIELD: chemistry.

SUBSTANCE: invention refers to compounds of the formula (I): , where R1 is C1-C8alkyl optionally substituted with one to three substitutes selected out of substitute group A; R2 is C1-C6alkyl or C1-C6alkoxyC1-C6alkyl; R3 is C1-C6alkyl or C1-C6alkoxy; or R2 and R3 together with adjoining carbon atoms form optionally substituted non-aromatic 5-10-member carbon ring; R4 is hydrogen; G is group represented by the formula: or the rest as provided in the invention claim; and to pharmaceutical composition, application of claimed compounds, and method of atopic dermatitis prevention or treatment.

EFFECT: novel compounds useful as atopic dermatitis treatment medication and antipruritic medicines.

24 cl, 75 ex, 290 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to benzopyran derivatives of formula or

or their pharmaceutically acceptable salts, where R1 and R2 independently represent a hydrogen atom or a C1-6alkyl group, R3 is a hydroxyl group, R4 is a hydrogen atom, m is an integer ranging from 1 to 4, n is an integer ranging from 0 to 4, V is a single bond, CR7R8 or NR9, R5 is a hydrogen atom, R6 is a hydrogen atom, C1-6alkyl group, C3-8cycloalkyl group, C3-8cycloalkenyl group, amino group, C1-6alkylamino group, C6-14aryl group, C2-9heteroaryl group or C2-9heterocyclic group, A is a 5- or 6-member ring condensed with a benzene ring, and the ring can contain an oxygen atom, a nitrogen atom or a sulphur atom numbering from 1 to 3 or separately, or combined, the number of unsaturated bonds in the ring equals 1, 2 or 3, including the unsaturated bond in the condensed benzene ring, carbon atoms in the ring can represent carbonyl or thiocarbonyl.

EFFECT: compounds can be used as antiarrhythmic agents.

47 cl, 1 tbl, 98 ex

FIELD: medicine.

SUBSTANCE: invention refers to new pyridine derivatives or to their pharmaceutically acceptable salts of general formula 1: wherein R1, R2, R3, R4, R5, R6 and R7 are independently chosen from the group including hydrogen atom, halogen, amino, C1-C6lower alkyl, C2-C6lower alkenyl, C1-C6lower alkoxy, C1-C10alkylamino, C4-C9cycloalkylamino, C4-C9heterocycloalkylamino, C1-C10aralkylamino, arylamino, acylamino, saturated heterocyclyl, acyloxy, aryl, heteroaryl, C1-C10aralkyl, aryloxy; X represents oxygen or sulphur atom; Y represents oxygen atom or N-R8, wherein R8 is chosen from the group including hydrogen atom; aforesaid aryl group is chosen from phenyl, naphthyl and condensed phenyl group; aforesaid heteroaryl and saturated heterocyclic groups represent pentagonal or hexagonal heterocyclic ring containing 1 to 2 heteroatoms chosen from oxygen, nitrogen and sulphur atom; or condensed heterocyclic ring; and aforesaid aryl and heteroaryl groups are those that 1 to 4 assistants chosen from group including halogen, C1-C6lower alkyl, C1-C6lower alkoxy are substituted. And specified compounds or their pharmaceutically acceptable salt of formula 1 are not compounds as follows 6-methyl-3,4-dihydro-pyrano[3,4-c]pyridin-1-one, 5-vinyl-3,4-dihydro-pyrano[3,4-c]pyridin-1-one, 6-methyl-8-furan-2-yl-3,4- dihydropyrano[3,4-c]pyridin-1-one, 3-tert-butyl-5,6,7,8-tetrahydro-[2,7]naphthyridine-8-one and dimethyl ether (3S)-6,8-dimethyl-1-oxo-1,2,3,4-tetrahydro-[2,7]naphthyridine-3,5-dicarboxylic acids.

EFFECT: compounds possess inhibitory action with respect to formation of cytokines involved in inflammatory reactions, can be used as a therapeutic agent for treatment of inflammatory diseases, immune diseases, chronic inflammations; it provides antiinflammatory and analgesic action.

21 cl, 7 tbl, 144 ex

FIELD: chemistry.

SUBSTANCE: invention refers to new spirocyclic cyclohexane derivatives of general formula I , where: R1-R3, R5-R10, W, X are disclosed in the claim 1 of formula.

EFFECT: compounds exhibit analgesic activity to be applied for making a medical product for pain therapy.

20 cl, 1 tbl, 54 ex

FIELD: chemistry; pharmacology.

SUBSTANCE: present invention relates to new condensed dicyclic nitrogen-containing heterocycles with the general formula (I), their pharmaceutically accepted salts and stereoisomers, possessing DGAT inhibiting action. In the compound of formula (I): , X is selected from a group, which consists of C(R1) and N; Y is selected from a group, which consists of C(R1), C(R2)(R2), N and N(R2); Z is selected from a group, which consists of O; W1 is selected from cyclo(C3-C6)alkyl, aryl and 5- or 6-member heteroaryl, containing 1-2 heteroatoms, selected from a group, which comprises of nitrogen and sulphur, W2 selected from cyclo(C3-C8)alkyl, (C5-C6)heterocycloalkyl, containing 1 or 2 heteroatoms, selected from groups, consisting of nitrogen or oxygen, benzol and 5-or 6-member heteroaryl, containing 1-2 nitrogen atoms as heteroatoms, L1 is the link; L2 is selected from a group consisting of links, 0, (C1-C4)alkylene and (C1-C4)oxyalkylene; m denotes 0 or 1; its not a must that when m denotes 1 and L2 denotes a link, the substitute for W2 can be integrated with the substitute for W1 forming a 5-or 6-member ring, condensed with c W1 forming a spiro-system or condensed with W2, where specified ring could be saturated or unsaturated and has 0 or 1 atom O, as a member of the ring R1 is H; R2 is H; R3 and R4 are independently selected from groups consisting of H and (C1-C8) alkyl; optionally, R3 and R4 can together form 3-, 4-, 5- or 6-member spirorings, R5 and R6 are independently H; optionally, when Y includes the group R1 or R2, R5 or R6 can be joined with R1 and R2 forming a 5- or 6-member condensate ring, containing a nitrogen atom, to which R5 or R6 are joined, and optionally containing an oxo-group; R7 is selected from a group, composed of H, (C1-C8) alkyl, halogen(C1-C4)alkyl, 0Ra and NRaRb ; Ra selected from groups composed of H and (C1-C8)alkyl; and Rb selected from groups consisting of H and (C1-C8)alkyl; a dotted line indicates a possible bond. The invention also relates to pharmaceutical compositions and applications of the compounds.

EFFECT: obtaining compounds which can be used for getting medicinal agents to treat or prevent diseases or a mediated action state of DGAT, such as obesity, diabetes, syndrome X, resistance of insulin, hyperglycemia, hyperinsulinemia, hypercholesterolemia, hyperlipidemia, hypertriglyceridemia, disease of non-alcoholic fatty infiltration of the liver, atherosclerosis, arteriosclerosis, coronary artery disease and myocardial infarction.

33 cl, 17 dwg, 11 tbl, 391 ex

FIELD: chemistry.

SUBSTANCE: claimed are novel pyrazole derivatives of formula II or its pharmaceutically acceptable salts, where C ring is selected from phenyl or pyridinyl ring and R2, R2', Rx and Ry are such as said in given description. C ring has ortho-substituent and is optionally substituted in non-ortho positions. R2 and R2' , optionally taken with their intermediate atoms, form condensed ring system, such s indazole ring, and Rx and Ry, optionally taken together with their intermediate atoms, form condensed ring system, such a quinazoline ring.

EFFECT: possibility to use compositions as inhibitors of protein kinases as inhibitors GSK-3 and other kinases and apply them for protein kinase-mediated diseases.

41 cl, 8 tbl, 423 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted of dihydropyranoindole-3,4-dione of formula I and formula II: where X stands for H, R1 stands for H, phenyl, benzyl, cycles of said phenyl and benzyl can be substituted with 1-3 substituents, selected independently on each other from group, which includes halogen, C1-C6-alkyl, C1-C6-perfluoroalkyl, -O-C1-C6-perfluoroalkyl, C1-C6-alkoxygroup; where R2 stands for H, -OH; R3 stands for H, phenyl, benzyl, benzyloxygroup, cycles of these groups can be optionally substituted with 1-3 substituents, selected independently on each other from group including phenyl, halogen, C1-C6-alkyl, C1-C6-perfluoroalkyl, -O-C1-C6-perfluoroalkyl, C1-C6-alkoxygroup, pharmaceutically acceptable salts of said compounds. Compounds demonstrate activity of inhibiting plasminogene activator inhibitor (PAI-1), which allows using them for production of medication for treatment of pathological states resulting from fibrinolytic disorders.

EFFECT: obtaining compounds, demonstrating activity in inhibiting plasminogene activator inhibitor which allows using them in pharmacology.

23 cl, 1 dwg, 1 tbl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof. In formula (I) Y is C-R4 and Z is CH; or Y is C-R4 and Z is N; or Y is N and Z is CH; R1 is a 5- or 6-member ring of formula (II) or (III): R2 is H, C1-C7-alkyl; R3 is phenyl, pyrazolyl, isoxazolyl, pyridinyl, pyrimidinyl or pyrazinyl, which can possibly be substituted with one, two or three substitutes selected from a group consisting of: CN, CI, F, Br, CF3, CHF2, C1-C7-alkyl, -O-C1-C7-alkyl, -(CH2)m-Rc, -O-CH2F, -O-CHF2, -O-CF3, -S(O)2-Rd; R4 is H, C1-C7-alkyl; R5 is H, CI, F, Br, CN, CF3, CHF2, C1-C7-alkyl, -C3-C6-cycloalkyl, -(CH2)m-Re or -(CO)-NRiRj; R6 is C1-C7-alkyl; R7 is H, CI, F, CN or C1-C7-alkyl; Rc is -OH; Rd is C1-C7-alkyl; Re is -CH2F, -CHF2, -CF3, CN, C1-C7-alkoxy; Ri, Rj independently denote H or C1-C7-alkyl; m equals 1-4. The invention also relates to a medicinal agent having mGluR5a receptor antagonist properties, containing one or more of the disclosed compounds as an active component.

EFFECT: high efficiency of the medicinal agent.

24 cl, 208 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel imidazole derivatives of general formula I and pharmaceutically acceptable salts thereof, where R1 is selected from a group comprising aryl and alkyl, optionally substituted hydroxy; R2 is selected from a group comprising hydrogen and alkyl; R3 is selected from a group comprising hydrogen and -X-A, where X is selected from a group comprising -C(O)- and -S(O)2-; and A is selected from a group comprising hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycle and optionally substituted cycloalkyl, where the optionally substituted groups are substituted with 1-2 substitutes selected from a group comprising alkyl, substituted alkyl, alkoxy, substituted amine which is a -NRR group, substituted aryloxy, heteroaryl, heterocycle, halogen, hydroxy and -S(O)2-R9, where R9 is an alkyl; or R1 and R3 together with a carbon atom bonded to R1 and a nitrogen atom bonded to R3 form a heterocyclic or substituted heterocyclic group; R4 is selected from a group comprising hydrogen, linear alkyl, -alkylene-aminoacyl-, -alkylene-hydroxy-, -[alkylene]p-nitrogen-containing heterocycle, -[alkylene]p-nitrogen-containing substituted heterocycle, -[alkylene]p-nitrogen-containing heteroaryl, -[alkylene]p-nitrogen-containing substituted heteroaryl and -[alkylene]p-NR10R11, where p equals 0 or 1, the alkylene contains 1-5 carbon atoms and can have 1 or 2 substitutes selected from a group comprising amine, hydroxy and halogen, aminoacyl relates to a group -C(O)NRR, where each R is independently selected from a group comprising hydrogen and alkyl, R10 and R11 are independently selected from a group comprising hydrogen, alkyl, substituted alkyl, -S(O)2-alkyl, substituted aryl, substituted heteroaryl, cycloalkyl, or when R10 is hydrogen, R11 is hydroxy, alkoxy or substituted alkoxy; or when R1 and R3 together with carbon and nitrogen atoms respectively bonded to them do not form a heterocyclic or a substituted heterocyclic group, R3 and R4 together with a nitrogen atom to which they are bonded form a spiro-condensed heterocyclic group; R5 is selected from a group comprising L-A1, where L is selected from a group comprising C1-C5alkylene, where the alkylene is defined above; and A1 is selected from a group comprising aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle; and one of R6 or R7 is selected from a group comprising aryl and heteroaryl, each of which can optionally be substituted with -(R8)m, where m equals a whole number from 1 to 2, and the other of R6 or R7 is selected from a group comprising hydrogen, halogen and alkyl; or R6 as well as R7 denotes hydrogen; R8 is selected from a group comprising cyano, alkyl, -CF3, alkoxy, halogen, where alkyl, aryl, aryloxy, cycloalkyl, heterocycle, heteraryl and substituted alkyl, aryl, aryloxy, cycloalkyl, heterocycle and heteroaryl are described in claim 1. The invention also relates to specific compounds, a pharmaceutical composition based on the compound of formula I, a method of inhibiting KSP and use of the composition to prepare a medicinal agent.

EFFECT: novel imidazole derivatives are useful as kinesin spindle protein inhibitors for treating cancer.

25 cl, 27 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula as well as separate enantiomers, diastereomers, racemic mixures and pharmaceutically acceptable salts thereof, having mitotic kinesin KSP inhibiting activity, as well as inhibitory action on tumour cells, use thereof in preparing a medicinal agent and a pharmaceutical composition based on said compounds. In said formula, R denotes Z-NR2R3, Z-OH, Ar1 and Ar2 independently denote a phenyl which, if needed, is substituted with one or more groups independently selected from: F, CI, Br, I, OH, Z denotes an alkylene having 1-6 carbon atoms which, if needed, is substituted with C1-6alkyl, and R1 assumes values given in the claim.

EFFECT: improved method.

16 cl, 3 dwg, 124 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula (I) and to their pharmaceutically acceptable salts exhibiting P2X3 receptor antagonist activity. In formula (I), X represents -O-; Y represents -NRdRe where one of radicals Rd and Re means hydrogen, and the other means hydrogen; C1-C12alkyl; C5-C7cycloalkyl; C5-C7cycloalky-C1-C12alkyl; hydroxy-C1-C12alkyl; acetyl; aminocarbonyloxy- C1-C12alkyl or heterocyclyl representing a 6-members saturated ring containing heteroatom S substituted by two oxo groups; D represents optional oxygen; R1 represents isopropyl; R2 represents hydrogen; R5 represents hydrogen or C1-C12alkyl; R4 means hydrogen; C1-C12alkyl; halogen; halogen- C1-C12alkyl; C1-C12alkoxy; hydroxy; halogen- C1-C12alkoxy; nitro; amino; hydroxy- C1-C12alkyl; C1-C12alkoxyalkyl; hydroxy- C1-C12alkoxy; C1-C12alkylsulphonyl; cyano; heteroaryl representing a 5-members aromatic ring containing one, two or three heteroatoms selected from O, S and N which can be optionally substituted by a thio group, C1-C12alkyl or C1-C12alkylsulphonyl; heterocyclyl representing a 6-members saturated ring containing two heteroatoms N, one of which is substituted C1-C12alkylsulphonyl; -(CH2)m-(Z)n-(CO)-Rf or -(CH2)m-(Z)n-SO2-(NRg)n-Rf where each m and n independently represents 0 or 1, Z means NR8, Rf means C1-C12alkyl, hydroxy, amino or hydroxy- C1-C12alkyl, and Rg means hydrogen; R3 represents methoxy; R6 represents hydrogen; and one of radicals R7 and R8 represents hydrogen, and the other represents hydrogen, acetyl or phenyl.

EFFECT: also, the invention refers to a pharmaceutical composition and to an application of the compound of formula (I) for preparing a drug.

8 cl, 3 tbl, 70 ex

FIELD: medicine.

SUBSTANCE: in formula (I) , the ring A represents 6-members aryl or 5-6-members heteroaryl containing 1-2 heteroatoms selected from nitrogen and sulphur; Q means C3-8 cycloalkyl, 5-6-members heterocycle containing 1 heteroatom selected from oxygen, nitrogen or sulphur, C1-6 alkyl or C2-6 alkenyl; the ring T represents 5, 6, 9 or 10-members heteroaryl or 9-members heterocycle optionally additionally substituted by 1-3 heteroatoms independently selected from nitrogen or sulphur. The values of other substitutes are specified in the patent claim. Also, the invention refers to methods for preparing oxime derivatives of general formula (I), to pharmaceutical compositions containing the compound of the invention as an active ingredient and to applications of the compounds of the invention in preparing a drug.

EFFECT: compounds of the invention exhibit properties of a glucokinase activator.

33 cl, 1499 ex

FIELD: medicine.

SUBSTANCE: compounds can be used for treating neurological conditions, more specifically for treating neurodegenerative conditions, such as Alzheimer's disease. In a compound of formula I R2 represents H or CH2NR1R4 where R1 and R4 are independently selected from H, unsubstituted C1-6alkyl, substituted or unsubstituted C3-6 cycloalkyl, R3 represents H; substituted or unsubstituted C1-4alkyl; substituted or unsubstituted C2-4alkenyl; substituted or unsubstituted 6-members aryl condensed or uncondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl, containing 1-2 nitrogen atoms in a cycle; substituted or unsubstituted saturated or unsaturated 5 or 6-members N-containing heterocycle which can additionally contain nitrogen, oxygen or the sulphur atom condensed or ucondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl containing nitrogen in a cycle; (CH2)nR6 where n is an integer from 1 to 6, and the values of R6 and the values of other radicals are specified in the patent claim.

EFFECT: increased antiamyloidogenic action.

20 cl, 20 tbl, 6 dwg, 7 ex

FIELD: medicine.

SUBSTANCE: invention refers to chemical-pharmaceutical industry, and concerns a EP2 agonist which exhibits the EP3 agonist action, and induce a neurotising and/or protective effect and thereby is effective as a therapeutic agent for a peripheral nerve disease, such as lower and upper motor neuron disorder, nerve root disease, plexopathy, brachial plexus compression syndrome, peripheral neuropathy, neurofibromatosis and nervomuscular conduction disease.

EFFECT: EP2 agonist which exhibits the EP3 agonist action; it is a safe and effective neurotisation and/or protection agent which has an insignificant impact on the cardiovascular system.

13 cl, 36 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to hot or sweet flavourants in form of a synthetic amide compound or edible salt thereof in amount ranging from approximately 0.001 parts per million to approximately 100 parts per million. The amide compound has formula

where A is a phenyl or a 5- or 6-member heteroaryl ring selected from a group comprising pyridine, pyrazine, pyrazole, thiazole, furan, thiophene, benzofuran and benzothiophene; m equals 1, 2 or 3, each R1 is independently selected from hydroxyl, fluorine, chlorine, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy and isopropoxy, or alternatively two R1 are bonded to form a saturated C1-C3 alkylenedioxy ring on the phenyl; and R2 is a C3-C10 branched alkyl. The amide compound also has formula

in which substitutes A, B, R50, R60, R70, R80, n and m assume values given in the formula of invention. The amide compound is also a specific chemical compound.

EFFECT: obtaining hot and sweet taste modifiers and boosters for food and medicinal products.

39 cl, 7 tbl, 180 ex

Aromatic compound // 2416608

FIELD: chemistry.

SUBSTANCE: invention describes a novel compound of general formula (1), where radicals R1, R2, X1, Y and A are as described in claim 1 of the invention. The invention also describes a method of obtaining compounds of formula (1), as well as a pharmaceutical composition based on said compounds, for treating fibrosis.

EFFECT: novel compounds with excellent collagen formation suppression, cause fewer side-effects and which are safer are obtained.

62 cl, 2717 ex, 432 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (I) or pharmaceutically acceptable salts thereof, where Q is CH or N; R2 is C1-C4 alkyl or C3-C4-cycloalkyl; Y is R5-O; where R5 is propynyl; X is selected from a group consisting of aryl, heteroaryl, C1-C5-alkyloxy, heterocycloalkyl, arylamino, heteroarylamino, heteroaryl-C1-C4-alkylamino, aryloxy, aryl-C1-C2-alkyloxy or C3-C6-cycloalkyl-C1-C4-alkyloxy, each of which is optionally substituted with 1-3 times; the optional substitute(s) for X is(are) independently selected from a group comprising halogen, cyano, trifluoromethyl, nitro, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkyloxy-C1-C4-alkoxy, -SMe, SO2-C1-C2-alkyl, -NMe2, - C(O)O-C1-C5-alkyl, -SCF3, -SO2-NH2, -SO2-C2-alkyl-OH, -CONH2, -COMe, - CONH-C1-C4-alkyl, -CONMe2, -NHCOMe, -CH2COOEt, -OCH2COOEt, -CH2- cyclopropyl, and each R3 and R4 is H; where aryl denotes phenyl or naphthyl; heteroaryl denotes monocyclic or bicyclic hydrocarbon containing 5-10 ring atoms, one or more of which are heteroatoms selected from O, N or S; heterocyclyl denotes piperidinyl or benzodioxolyl; or a compound or pharmaceutically acceptable salt thereof, selected from a group comprising (4-dimethylaminophenyl)-[4-(4-cyclopropylphenyl)-6-propargyloxyquinazolin-2-yl]methanone, (3-sulphamoylphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, [3-(2-hydroxyethanesulphonyl)phenyl]amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, (3-methylsulphanylphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, (3-methanesulphonylphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, and (5-ethanesulphonyl-2-hydroxyphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4- dihydroquinazoline -2-carboxylic acid. The invention also relates to a pharmaceutical composition based on the compound of formula (I) and use of the compound of formula (I).

EFFECT: novel benzoquinazoline derivatives, which are useful in treating bone disorders, are obtained.

6 cl, 128 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to 5-nitrofuran derivatives of formula I: where R=piperidino, pyrrolidineo, diethylamino, morpholino.

EFFECT: presented preparation of new biologically active compounds which exhibit antimicrobial activity.

1 cl, 4 ex, 2 tbl

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