Photochromic 5'-vinyl-6-nitro-spirobenzopyran derivatives and production method thereof

FIELD: chemistry.

SUBSTANCE: present invention relates to novel derivatives of 5'-vinyl-6-nitro-spirobenzopyran of formula 1 , where R1=R2=H (SP2); R1=CN, R2=H (SP3); R1=CHO, R2=H(SP4); R1=NC2, R2=H(SP5); R1=CN, R2=CN(SP6); R1=CO2CH3, R2-CN(SP7); R1,R2=-C(O)-O-C(CH3)2-O-(O)C-(SP8), which have photochromic properties, as well as production methods thereof. Disclosed are methods for directed modification on the 5'-position of a photochrome molecule using well-known and simple experimental procedures of organic synthesis (Wittig and Horner-Emmons olefination, nucleophilic bonding on the carbonyl group of reactants containing active methyl or methylene groups: nitromethane, malonodinitrile, cyanoacetic acid and esters thereof, Meldrum acid).

EFFECT: method of producing substituted 5'-vinyl-indoline spirobenzopyrans is characterised by that the starting 5'-formyl derivative in the solution undergoes olefination with different CH-acids in the presence of corresponding bases in an argon atmosphere at high temperature of the reaction mixture.

4 cl

 

The present invention relates to new derivatives of photochromic spiropyrans (SP 2-8) and methods for their preparation, which can find application in various engineering fields when creating elements of an optical memory, copy materials, and environments, adjustable filters, eye protection from the powerful flashes of light radiation, as well as photochromic labels and markers to photoperiodicity activity of biological objects and polymer matrices, photochromic monomers and polymers.

Spectral properties and parameters of fotopriemami of spiropentane strongly depends on the nature existing in the molecule of Vice, therefore, directed the variation of these parameters allows for the search of new photochromes with the desired photochemical characteristics [Bertelson R.C. in: Photochromism. GH Brown (Ed). Wiley. N.Y. - 1971. - P. 49-294, 397-431. Sachsen E.R., Martynova VP, Efros PS Synthesis and properties of spiropyrans capable of reversible disclosure Pyrenophora rings. // Chemistry of heterocyclic compounds. - 1979. No. 2. - S-459].

Previously it was shown that the substitution on indolinone part of the molecule does not lead to significant changes of maximum absorption of a colored merocyanine form [Pancerny VI, Halberstam M.A., don N.A. ABOUT the influence of the substituents at positions 5 and 8' on the reaction rate of a dark discoloration of pothook Alannah solutions 1,3 .3m-trimethylspiro[indoline-2,2'-[2H-1]benzopyrano]. // Chemistry of heterocyclic compounds. 1973. No. 5. S-658; Pancerny VI, Halberstam M.A. ABOUT the influence of the substituents at positions 5 and 8' on the absorption spectra merocyanine forms of spiropyrans. Chemistry of heterocyclic compounds, 1973. No. 5. S-662]. These results have opened a new direction for directional introduction of reactive spacers of different nature by targeting modification indolinone fragment molecules spiropyran. Such systems, in which the reactive group introduced at position N1indolinone fragment molecules spiropyran, have been investigated in detail in [Willner I. Willner Century Biomaterials intergrated with electronic elements: en route to bioelectronics. // Trends in Biotechnology. - 2001. - V. 19. - P. 222-230; I. Willner, B. Willner Photoswitchable biomaterials as grounds for optobioelectronic devices. // Bioelectrochem. Bioenerg. - 1997. - V. 42. - P. 43-57].

At the same time, the emergence and development of new options for introducing a reactive anchor groups at other positions (5' or 7') indolinone fragment molecules spiropyran was hampered by a lack of simple and reliable melastatin methods for the synthesis of substituted derivatives indolenine required for the synthesis of modified photochromes in the classical way of obtaining spiropyranes by condensation of substituted derivatives indolenine or their Quaternary salts with substituted salicylic aldehydes. In the literature dealing with the e known only a few reactions of electrophilic substitution in a series of spiropyranes, suitable for direct modification of the molecule at the 5'-th position indolinone fragment. However, the structural diversity of the anchor function was severely limited by the following set of functional groups: NO2, Cl, Br, CN [Samoilov N.P., Halberstam M.A. Way to obtain 1,3 .3m-trimethyl-5,6'-dinitrourea(2 N-1'-benzopyran)-2,2'-indoline. As the USSR №455955. - Priority of 5.01.1975. - Bull. Fig. 1975. No. 1; Samoilova, for EXAMPLE, by a method of obtaining a 5-galization of benzopyranones. As the USSR №469696. - Priority of 5.05.1975. - Bull. Fig. - 1975. No. 17; Sachsen E.R., Zvenigorod L.A., Lesenok N.G., Martynova VP Bromination of spiropyranes and restore their nitro-derivatives. / The chemistry of heterocyclic compounds. 1977. No. 10. S-1326; Samoilova, NP, Halberstam M.A. ON some substitution reactions in a series of photochromic indolinospiropyrans. / The chemistry of heterocyclic compounds. 1977. No. 8. S-1068].

Known methods of obtaining a number of unsaturated derivatives spirometery containing various unsaturated substituents as paranavai and indolinone part of the molecule fotograma: 6 - or 8-vinylphosphonate [Kakurai T., Takano T. Photochromic compounds. // Patent of Japan JP 61076490. - publ. 18.04.1986; Miyashita, A. Preparation of spiropyran compounds as photochromic substances and optical materials. // Patent WO 9420502. - publ. 15.09.1994]; 5'-acrylamido-8-methoxy-6-nitro-1,3 .3m-trimethylindolenine [Mistry B.B., Patel R.G., V.S. Patel Synthesis and characterization of photochromic homoplymer/copolymer. // J. Applied Polymer Science. 1997. - V. 64, N 5. P.841-848]; 8-allyl-6-formylbenzoate [Lukyanov B.S., Metelitsa A.V., Lukyanova M.B., Mukhanov E.L., Borisenko N.I., Alekseenko Y.S., Bezugliy S.O. Photochromism of the Spiropyran Thin Solid Films. // Mol. Cryst. Liq. Cryst. - 2005. - V. 431. P.51-56]. A common disadvantage of the above methods is that they are multi-stage.

With the aim of developing new, more effective methods and approaches for the introduction of a photochromic labels based on the derivatives of spiropyrans in different systems and environments previously we had been offered the option of selective formirovaniya of spiropentane position 5' [Laptev A.V., Lukin, A., Belikov N.E., Shvets V.I., Demin OV, buraczewski VA, Hodonou AA 5-Formyl-substituted indolinone spirometery and the way they are received. // Patent RF №2358977, B. I. 2009, №17], which allowed us to develop an efficient procedure for obtaining valuable synthetic intermediates - 5'-formyl-substituted of spiropyrans. This simple and highly efficient method for the synthesis of 5'-formyl-derivatives greatly expanded synthetic potential of their use as starting compounds for the directed modification on the 5'-position of the molecule photochrome using well-known and simple experimental procedures of organic synthesis (referirovanija by Wittig and Horner-Emmons, nucleophilic attach by a carbonyl group reagents containing an active metal or met the Lenovo group: nitromethane, malonodinitrile, tsianuksusnym acid and its esters, acid, Meldrum).

Closest to the proposed invention, the technical solution is a way of turning the previous Sinton on the example of the research process referirovanija by Horner-Emmons with 3-[6-nitro-1',3',3'-trimethylspiro([2H]-1'-chromen-2,2'-indolin-5'-yl)]propanolol acid and its ethyl ester [Avepa, Ayuki, Neelikon, Revesco, Vasaraasia, Ovemen, S.D., Whisper, Dev. Synthesis and study of the photochromic properties of 3-[6'-nitro-1,3 .3m-trimethylspiro(indoline-2,2'-[2H]chromen-5-yl)]propanolol acid and its ethyl ester. // High energy chemistry, 2010, T. 44, No. 3, S-243].

The shortcoming of the above methods of synthesis are the low total yield of the target compounds.

The technical result of the present invention is a method of obtaining new derivatives of 5'-vinyl-6-nitro-spirometery (SP 2-8) (see scheme 1) and the study of their photochromic properties.

The technical result of the invention is achieved by the fact that 6-nitro-5'-formyl-1',3',3'-trimethylspiro(2H-1'-chromen-2,2'-indoline) (SP 1) is subjected to rafinirovaniyu by the Wittig ridom generated by the action of potassium tert-butylate at bromide triphenylphosphine in anhydrous tetrahydrofuran in an inert atmosphere; or the nucleophilic attach by a carbonyl GRU is PE reagents containing the active metal or a methylene group, when carbonyl precursor is subjected to the action of excess (1.1-3 EQ.) various CH-acids in the presence of appropriate bases at elevated temperature in an inert atmosphere, with simultaneous azeotropic distillation or chemical binding of water; or rafinirovaniyu by Horner-Emmons anion of diethyl(cyanomethyl)phosphonate, followed by reduction of the intermediate nitrile by diisobutylaluminium at -80°C. the Novelty of the claimed indication is used as a photochromic structures of the new fragments and functional groups other than the structure closest analogue.

Scheme 1. The method of preparation and the structure of new derivatives of 5'-vinyl-6-nitro-spirometery (SP 2-8).

where

No. of connectionsR1R2
SP2NN
SP3CNN
SP4SNON
SP5NO2 N
SP6CNCN
SP7CO2CH3CN
SP8-C(O)-O-(CH3)2-O-(O)S-

5'-Vinyl-6-nitro-spirometery (SP-2) was obtained by rafinirovannom by Wittig source (SP 1) ridom generated by the action of potassium tert-butylate at bromide triphenylphosphine in anhydrous tetrahydrofuran. The aldehyde (SP-4) was synthesized by rafinirovannom by Horner-Emmons source (SP 1) anion of diethyl(cyanomethyl)phosphonate, followed by reduction of the intermediate nitrile (SP 3) diisobutylaluminium.

Nitroaniline derived (SP-5) was prepared by heating at 50°C in an inert atmosphere a solution of the original (SP 1) in absolute methyl alcohol in the presence of nitromethane and diacetate of ethylendiamine. Bis-substituted derivatives (SP 6) and (SP-7) were obtained by heating at boiling source (SP 1) in the system (ammonium acetate, glacial acetic acid, benzene) with malonodinitrile or methyl ether tsianuksusnogo acid, respectively. The method of receiving spiropyran (SP 8) included the interaction of acid, Meldrum with the original aldehyde (SP 1) when heated in ethanol at PR is the presence of piperidine and molecular sieves (to associate a spin-off of water).

In contrast to the syntheses of compounds (SP 2-7), where the original spiropyran (SP 1) were subjected to full conversion within 1-2 h, obtaining spirometery (SP 8) requires more stringent conditions - heating the reaction mixture for 6-8 hours All reactions were carried out in oxygen-free atmosphere and degassed solvents, in a stream of argon or nitrogen, because the target vinology (SP 2-8) are prone to oxidative degradation. All of these methods used a slight excess of the reagent (1.1-3 EQ.) in relation to the original 5'-formylkynurenine (SP 1).

Table 1
The spectral characteristics of the derivatives of spiropyran (SP 2-8) in solutions
ConnectionSolventλAndNMλInNM
Ethanol277, PL547
Toluene<300575 square, 615
Ethanol346 567
Toluene347590 square, 628
Ethanol364567
Toluene357590 square, 628
Ethanol404568
Toluene390590 square, 628
Ethanol409587
Toluene403620
Ethanol398576
Toluene391603 square, 637
Ethanol43055
Toluene418605 square, 640
Note: λAndand λInthe maxima of the absorption bands of the initial and photoinduced forms, respectively.

Target photochrome (SP 2-8) were obtained from outputs from 43%to 85%, in preparative quantities, the structure of all compounds was characterized by a set of physicochemical methods of analysis.

These spirometery (SP 1-8) are photochromic compounds, the spectral characteristics of their solutions in toluene and ethanol are given in table 1.

For illustration of the present invention described below the following examples of experimental procedures.

Example 1. The method of obtaining 5'-vinyl-6-nitro-1',3',3'-trimethylspiro(2N-1-chromen-2,2'-indoline) (SP 2).

To a solution of 2.0 g (5.7 mmol) of 6-nitro-5'-formyl-1',3',3'-trimethylspiro(2H-1'-chromen-2,2'-indoline) (SP 1) and 3.0 g (8.4 mmol) of bromide triphenylphosphine in 50 ml of anhydrous tetrahydrofuran was added 1.0 g (8.9 mmol) of potassium tert-butylate and was heated at 50°C for 1 h in argon atmosphere with stirring on a magnetic stirrer. Then the reaction mass was added 50 ml of distilled water and neutralized mixture of 10%hydrochloric acid. Then spent the extraction of the reaction mixture several p is rceme methylene chloride (3 times 50 ml), the extracts were combined, dried over anhydrous sodium sulfate, the solvent was removed. For separation of the target product used flash chromatography on silica gel, eluent - petroleum ether (BP. 40-70°C) - methylene chloride (2:1, by volume). Received 1.5 g (4.3 mmol) of the product (SP 2) (76%), white crystals (darken and turn storage) with TPL 144-145°C. Rf0.85 (methylene chloride, "Silufol UV-254, (Kavalier, Czech Republic), detection of spots - the impact on the developed plate natural light).

An NMR spectrum1H (CDCl3, δ, ppm, J/Hz): 1.19 (3H, s, 3 a-CH3), 1.31 (3H, s, 3'b-CH3), 2.74 (3H, s, 1'-CH3), 5.07 (1H, DD, J 11.0/1.0, 2-N-vinyl trans), 5.59 (1H, DD, J 17.5/1.0, 2-N-vinyl cis), 5.84 (1H, d, J 10.4, 3-H), 6.49 (1H, d, J 7.9, 7'-H), 6.69 (1H, DD, J 17.5/11.0, 1-H-vinyl), 6.76 (1H, d, J 8.2, 8-H), 6.92 (1H, d, J 10.4, 4-H), 7.18 (1H, d, J 1.7, 4'-H), 7.22 (1H, DD, J 7.9/1.7, 6'-H), 7.99 (1H, s, 5-H), 8.01 (1H, DD, J 8.2/2.7, 7-H).

UV spectrum of [(EtOH), λmax, nm (log ε)]: 277 (4.70), pl. 323 (4.38).

Mass spectrum [m/z, IRel]: 348 (M+, 83), 333 (25), 185 (100), 170 (23).

Found (%): 71.98; N, 5.93; N, 8.02. With21H20N2About3. Calculated (%): 72.40; H 5.79; N, 8.04.

Example 2. The way to obtain E-3-[6-nitro-1',3',3'-trimethylspiro(2H-1'-chromen-2,2'-indoline)-5'-yl]prop-2-isonitrile (SP-3).

To a suspension of 75 mg (1.87 mmol) of sodium hydride (content of sodium hydride in mineral oil 60%) in 10 ml of anhydrous THF, pre-cooled in an ice bath to 0°C. in the argon atmosphere is ri vigorous stirring on a magnetic stirrer was added dropwise via syringe 0.3 ml (1.70 mmol) of diethyl(cyanomethyl)phosphonate (C 2-phosphonate). After 30 min stirring to the resulting solution was added in portions of 0.5 g (1.43 mmol) of 6-nitro-5'-formyl-1',3',3'-trimethylspiro(2H-1'-chromen-2,2'-indoline) (SP-1). After 1 h stirring to the mixture was added 10 ml of distilled water and bring the pH value to 6 using 0.1 M hydrochloric acid. Then carried out the extraction of the reaction mixture methylene chloride (3 times 50 ml), the extracts were combined and dried over anhydrous sodium sulfate, the solvent was removed on a rotary evaporator. For separation of the target product was used by column chromatography on silica gel. The fractions containing the target compound (SP-3), were combined, the solvent was removed, the residue was dried in vacuum for 1 h with 0.2 mm Hg Additionally, the product was purified by crystallization from alcohol.

Yield: 0.45 g (1.21 mmol) of (85%), yellow crystals TPL 205-207°C. Rf0.47 (methylene chloride-petroleum ether 3: 1 (by volume), Kieselgel 60F254(Merck, Germany), detection of spots - the impact on the developed plate visible light).

1H-NMR spectrum (CDCl3, δ, ppm, J/Hz): 1.18 (3H, s, 3 a-CH3), 1.30 (3H, s, 3'b-CH3), 2.80 (3H, s, 1'-CH3), 5.66 (d, 1H, J 16.1. 2"-H), 5.83 (1H, d, J 10.3, 3-H), 6.53 (1H, d, J 8.2, 7'-H), 6.77 (1H, d, J 8.5, 8-H), 6.95 (1H, d, J 10.3, 4-H), 7.17 (1H, d, J 1.7, 4'-H), 7.28 (1H, DD, J 8.2/1.7, 6'-H), 7.33 (d, 1H, J 16.1, 3"-H), 8.01 (1H, s, 5-H), 8.03 (1H, DD, J 8.5/2.8, 7-H).

Mass spectrum [m/z, IRel]: 373 (M+, 100).

The UV spectrum of the [(EtOH), λmax, nm (log ε)]: 224 (4.28); 265 (4.27); 348 (4.50).

Found (%): 70.38; N, 5.53; N, 11.21. With22H19N3About3. Calculated (%): 70.76; H 5.13; N, 11.25.

Example 3. The way to obtain E-3-[6-nitro-1',3',3'-trimethylspiro(2H-1'-chromen-2,2'-indoline)-5'-yl]prop-2-inala (SP 4).

A solution of 250 mg (0.67 mmol) of the compound (SP-3) in 5 ml of absolute methylene chloride was placed in the reactor, providing a constant current of argon and good stirring on a magnetic stirrer. Immersed in the reactor in an acetone bath and cooled it to -80°C using liquid nitrogen.

Was added to the reactor with stirring dropwise via syringe 0.6 ml 1.5 M (20 wt.%) solution diisobutylaluminium in toluene, after completion of the reaction was slowly raised the temperature of the bath to 0°C. Neutralization of the reaction mixture produced 1 g water 5 g of aluminum oxide. The reaction mass was filtered on a glass filter, washed with two portions of methanol (10 ml), the solvent was removed in vacuum. For separation of the target product was used by column chromatography on aluminium oxide. The fractions containing the target compound (SP 4), were combined, the solvent was removed, the residue was dried in vacuum for 1 h with 0.2 mm Hg Additionally, the product was purified by crystallization from alcohol.

Yield: 126 mg (0.34 mmol) (50%), yellow crystals, TPL 215-217°C. Rf0.16 (methylene chloride-petroleum ether 3: 1 (by volume), Kieslgel 60F 254(Merck, Germany), detection of spots - the impact on the developed plate visible light or 2,4-dinitrophenylhydrazine).

1H-NMR-spectrum (Dl3, δ, ppm, J/Hz): 1.20 (3H, s, 3 a-CH3), 1.32 (3H, s, 3'b-CH3), 2.80 (3H, s, 1'-CH3), 5.83 (1H, d, J 10.3, 3-H), 6.57 (1H, d, J 8.1, 7'-H), 6.60 (1H, DD, J 15.7/7.8, 2"-H), 6.77 (1H, d, J 8.3, 8-H), 6.96 (1H, d, J 10.3, 4-H), 7.30 (1H, d, J 1.7, 4'-H), 7.42 (1H, DD, J 8.1/1.7, 6'-H), 7.43 (1H, d, J 15.7, 3"-H), 8.02 (1H, s, 5-H), 8.03 (1H, DD, J 8.3/2.8, 7-H), 9.63 (1H, d, J 7.8, 1"-SNO).

Mass spectrum [m/z, IRel]: 376 (M+, 100).

UV spectrum of [(tO), λmax, nm (log ε)]: 229 (4.29); 258 (4.28); 365 (4.56).

Found (%): 69.72; H 5.45; N, 7.05. C22H20N2O4. Calculated (%): 70.20; H 5.36; N, 7.44.

Example 4. The method of obtaining E-6-nitro-5'-(2-nitro-1-ethynyl)-1',3',3'-trimethylspiro(2H-1'-chromen-2,2'-indoline) (SP 5).

To a solution of 0.5 g (1.4 mmol) of 6-nitro-5'-formyl-1',3',3'-trimethylspiro(2H-1'-chromen-2,2'-indoline) (SP 1), 300 ml (4.3 mmol) of nitromethane in 30 ml of absolute methanol was added with stirring 100 mg (0.6 mmol) of the diacetate of ethylendiamine and was heated at 50°C for 1 h in argon atmosphere with stirring on a magnetic stirrer. Then the solvents from the mixture was removed, the residue was dissolved in methylene chloride and washed with distilled water. For separation of the target product used flash chromatography on silica gel, eluent - petroleum ether (BP. 40-70°C) - methylene chloride (1:1, poojaa). Additionally, the product was purified by crystallization from ethyl alcohol. Obtained 0.35 g (0.9 mmol) of the product (SP 5) (64%), pink crystals with TPL 185-187°C. Rf0.7 (methylene chloride, "Silufol UV-254, (Kavalier, Czech Republic), detection of spots - the impact on the developed plate natural light).

An NMR spectrum1N (Dl3, δ, ppm, J/Hz): 1.20 (3H, s, 3 a-CH3), 1.32 (3H, s, 3'b-CH3), 2.82 (3H, s, 1'-CH3), 5.84 (1H, d, J 10.2, 3-H), 6.59 (1H, d, J 8.2, 7'-H), 6.68 (1H, d, J 9.5, 8-H), 6.98 (1H, d, J 10.2, 4-H), 7.27 (1H, d, J 1.7, 4'-H), 7.41 (1H, DD, J 8.2/1.7, 6'-H), 7.56 (1H, d, J 13.6, 2-H-vinyl), 7.99 (1H, d, J 13.6, 1-H-vinyl), 8.01 (1H, s, 5-H), 8.03 (1H, DD, J 9.5/2.7,7-H).

UV spectrum of [(tO), λmax, nm (log ε)]: 404 (4.57).

Mass spectrum [m/z, IRel]: 393 (M+, 84), 378 (28), 230 (100), 183 (56), 168 (34), 159 (46), 147 (28), 115 (32).

Found (%): 63.58; N, 5.33; N, 9.92. C21H19N3O5. Calculated (%): 64.12; N, 4.87; N, 10.68.

Example 5. The way to obtain E-3-[6-nitro-1',3',3'-trimethylspiro(2H-1'-chromen-2,2'-indoline)-5'-yl]-2-cyanoprop-2-isonitrile (SP 6).

A mixture of 1.0 g (2.9 mmol) of 6-nitro-5'-formyl-1',3',3'-trimethylspiro(2H-1'-chromen-2,2'-indoline) (SP 1), 0.2 g (3.2 mmol) of ammonium acetate, 0.38 g (5.7 mmol) of malonodinitrile, 20 ml of glacial acetic acid and 100 ml of benzene in a period of 1.5 h was heated at boiling under stirring on a magnetic stirrer with a nozzle Dean-stark, fending off the water (azeotropic distillation). After cooling to room temperature the reaction mixture is washed with 100 ml of water is, 100 ml saturated sodium bicarbonate solution, dried over sodium sulfate and drove the solvent. For separation of the target product used flash chromatography on silica gel, eluent - petroleum ether (BP. 40-70°C) - methylene chloride (1:1, by volume). Additionally, the product was purified by crystallization from ethyl alcohol. Obtained 0.9 g (2.3 mmol) of the product (SP 6) (78%), yellow crystals with TPL 168-170°C. Rf0.63 (methylene chloride, "Silufol UV-254, (Kavalier, Czech Republic), detection of spots - the impact on the developed plate natural light).

An NMR spectrum1H (CDCl3, δ, ppm, J/Hz); 1.20 (3H, s, 3 a-CH3), 1.33 (3H, s, 3'b-CH3), 2.87 (3H, s, 1'-CH3), 5.83 (1H, d, J 10.3, 3-H), 6.61 (1H, d, J 8.4, 7'-H), 6.79 (1H, d, J 8.5, 8-H), 6.99 (1H, d, J 10.3, 4-H), 7.58 (1H, s, 5'-CH=), 7.72 (1H, DD, J 8.4/2.0, 6'-H), 7.78 (1H, d, J 2.0,4'-H), 8.04 (1H, s, 5-H), 8.05 (1H, DD, J 8.5/2.8, 7-H).

UV spectrum of [(tO), λmax, (log ε)]: 409 (4.59).

Mass spectrum [m/z, IRel]: 398(M+, 17), 383 (10), 235 (100), 220 (28).

Found (%): 68.90; N, 5.03; N at 13.92. With23H18N4O3. Calculated (%): 69.34; N, 4.55; N, 14.06.

Example 6. The way to obtain methyl ester [6-nitro-1',3',3'-trimethylspiro(2H-1'-chromen-2,2'-indoline)-5'-yl]-2-cyanoprop-2-ene acid (SP 7).

A mixture of 1.0 g (2.9 mmol) of 6-nitro-5'-formyl-1',3',3'-trimethylspiro(2H-1'-chromen-2,2'-indoline) (SP 1), 0.2 g (3.2 mmol) of ammonium acetate, 0.6 g (6.1 mmol) of methyl ether tsianuksusnogo acid, 20 ml of ice-cold vinegar is Oh acid and 100 ml of benzene for 2 h was heated at boiling under stirring on a magnetic stirrer with a nozzle Dean-stark fending off the water (azeotropic distillation). After cooling to room temperature the reaction mixture is washed with 100 ml water, 100 ml saturated sodium bicarbonate solution, dried over sodium sulfate and drove the solvent. For separation of the target product used flash chromatography on silica gel, eluent - petroleum ether (BP. 40-70°C) - methylene chloride (1:1, by volume). Additionally, the product was purified by crystallization from ethyl alcohol. Received 0.8 g (1.9 mmol) of the product (SP 7) (66%), yellow crystals with TPL 178-180°C. Rf0.52 (methylene chloride, "Silufol UV-254, (Kavalier, Czech Republic), detection of spots - the impact on the developed plate natural light).

An NMR spectrum1H(CDCl3, δ, ppm, J/Hz): 1.21 (3H, s, 3 a-CH3), 1.34 (3H, s, 3'b-CH3), 2.85 (3H, s, 1'-CH3), 3.89 (3H, s, O-CH3), 5.83 (1H, d, J 10.3, 3-H), 6.60 (1H, d, J 8.3, 7-H), 6.78 (1H, d, J 8.4, 8'-H), 6.97 (1H, d, J 10.3, 4-H), 7.83 (1H, DD, J 8.3/1.9, 6'-H), 7.89 (1H, d, J 1.9, 4'-H), 8.02 (1H, s, 5-H), 8.03 (1H, DD, J 8.3/2.7, 7-H), 8.15 (1H, s, 5'-CH=).

UV spectrum of [(tO), λmax, nm (log ε)]: 398 (4.44).

Mass spectrum [m/z, IRel]: 431(M+, 72), 416 (20), 268 (100), 253 (20).

Found (%): 66.45; N, 5.33; N, 9.52. With24H21N3O5. Calculated (%): 66.81; N, 4.91; N, 9.74.

Example 7. The way to obtain 2,2-dimethyl-5-{[6-nitro-1',3',3'-trimethylspiro(2H-1'-chromen-2,2'-indoline)-5'-yl]methylene}-1,3-dioxane-4,6-dione (SP 8).

A mixture of 0.5 g (1.4 mmol) of 6-nitro-5'-formyl-1',3',3'-trimethyl the ro(2H-1'-chromen-2,2'-indoline) (SP 1), 0.4 g (2.8 mmol) of the acid of Meldrum, 0.2 g (2.4 mmol) of piperidine in 50 ml of ethanol was heated at 50°C for 8 h in an argon atmosphere with stirring on a magnetic stirrer in the presence of molecular sieves 4. Then removed from the mixture solvent, the residue was dissolved in methylene chloride, washed with 5%hydrochloric acid. For separation of the target product used flash chromatography on silica gel, eluent - petroleum ether (BP. 40-70°C) - methylene chloride (1:2, by volume). Additionally, the product was purified by crystallization from ethyl alcohol.

Received 0.3 g (0.6 mmol) of the product (SP-8) (43%), yellow crystals with TPL 194-196°C. Rf0.34 (methylene chloride, "Silufol UV-254, (Kavalier, Czech Republic), detection of spots - the impact on the developed plate natural light).

An NMR spectrum1H (CDCl3, δ, ppm, J/Hz): 1.21 (3H, s, 3 a-CH3), 1.34 (3H, s, 3'b-CH3), 1.78 (6N, s, 2-(CH3)2-dioxane), 2.86 (3H, s, 1'-CH3), 5.84 (1H, d, J 10.3, 3-H), 6.61 (1H, d, J 8.4, 7'-H), 6.79 (1H, d, J 8.5, 8-H), 6.98 (1H, d, J 10.3. 4-H), 8.03 (1H, s, 5-H), 8.05 (1H, DD, J 8.5/2.7, 7-H), 8.07 (1H, DD, J 8.4/1.8, 6'-H), 8.28 (1H, d, J 1.8, 4'-H), 8.37 (1H, s, 5'-CH=).

UV spectrum of [(tO), λmax, nm (log ε)]: 430 (4.38).

Mass spectrum [m/z, IRel]: 476(M+,24), 374 (16), 359 (12), 211 (100), 196 (14), 182(27), 168 (13). Found (%): 65.05; H 5.42; N, 5.72. With26H24N2O7. Calculated (%): 65.54; H 5.08; N, 5.88.

1. Production is s 5'-vinyl-6-nitrospiropyran General formula

where R1=R2=H (SP2); R1=CN, R2=H (SP3); R1=CHO, R2=H(SP4); R1=NO2, R2=H(SP5); R1=CN, R2=CN(SP6); R1=CO2CH3, R2-CN(SP7); R1,R2=-C(O)-O-(CH3)2-O-(O)C-(S8)possessing photochromic properties.

2. The method of obtaining substituted derivatives of 5'-vinyl-6-nitrospiropyran General formula where R1=R2=H (SP2), wherein the 6-nitro-5'-formyl-1',3',3'-trimethylspiro(2H-1'-chromen-2,2'-indoline) (SP1) are rafinirovaniyu by the Wittig ridom generated by the action of potassium tert-butylate at bromide methyltriphenylphosphonium in anhydrous tetrahydrofuran in an inert atmosphere.

3. The method of obtaining substituted derivatives of 5'-vinyl-6-nitrospiropyran General formula where R1=CN, R2=H (SP3) or R1=CHO, R2=H (SP4), wherein the 6-nitro-5'-formyl-1',3',3'-trimethylspiro(2H-1'-chromen-2,2'-indoline) (SP1) are rafinirovaniyu by Horner-Emmons anion of diethyl(cyanomethyl)phosphonate, followed by reduction of the intermediate nitrile (SP3) diisobutylaluminium in the atmosphere of argon at -80°C.

4. The method of obtaining substituted derivatives of 5'-vinyl-6-nitrospiropyran General formula (SP5-8), characterized in that 6-nitro-5'-formyl-1',3',3'-trimethylspiro(2H-1'-chromen-2,2'-indoline) (SP1) is subjected nuclei is linoma connection by a carbonyl group reagents, containing the active metal or a methylene group, through the action of the excess (1.1 - 3 EQ.) various CH-acids in the presence of appropriate bases at elevated temperatures (50-80°C), in an inert atmosphere, with simultaneous azeotropic distillation or chemical binding of water.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds, specifically to 4-substituted-3-(1-alkyl-2-chloro-1H-indol-3-yl)furan-2,5-diones of general formula I , where R1=H, C1-C6 alkyl; R2=H, C1-C6 alkyl, C1-C6 alkoxy; R3=phenyl, naphthyl, 2-phenyl-1-ethenyl, thienyl, furyl, pyrrolyl, benzothiophenyl, benzofuranyl, indolyl, synthesis method thereof and use as compounds capable of photochemical generation of stable fluorophores of formula II, which can be used, for instance in information storage systems, particularly as photosensitive components of material for three-dimensional recording and storage of information. The invention also relates to novel 4,5-substituted-6-alkyl-1H-furo[3,4-c]carbazole-1,3(6H)diones of general formula II , where R1=H, C1-C6 alkyl; R2=H, C1-C6 alkyl, C1-C6 alkoxy; R4=H, R5=phenyl, R4, R5=benzo, naphtho, thieno, furo, pyrrolo, benzothieno, benzofuro, indolo, method for synthesis of said compounds and use as fluorophores.

EFFECT: obtaining novel compounds and possibility of using said compounds as fluorophores.

14 cl, 2 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to new compounds, and more specifically to 5-formyl-substituted indoline spirobenzopyrans with general formula 1 where R1, R2 - Alk or c-Alk; R3 -CHO or NO2 group (electron-acceptor substitute), with photochromic properties. The invention also relates to the method of producing 5-formyl substituted derivatives of indoline spirobenzopyrans with formula 1. Spirobenzopyrans, which have electron-acceptor substitutes in the pyran part of the molecule, are subjected to direct selective formylation in position 5 in a trifluoroacetic acid medium with urotropine (hexamethylenetetramine) at boiling point of the mixture in an inert atmosphere for 1-1.5 hours. The obtained 5-formyl-substituted spirobenzopyrans are photochromic compounds are photochromic and can be used for making new photochromic materials (recording devices or information storage; photo-switching activity of biological objects and polymer matrices, complex formation; information security media, maps, special document protection equipment) or as advanced initial compounds for further synthesis of a large number of new photochromic objects.

EFFECT: wider field of application of the compounds.

2 cl, 1 tbl, 3 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for preparing 3,4-diaryl(hetaryl)maleimides of the formula (I): wherein R means (C1-C4)-alkyl or benzyl, or phenyl; R1 means bromine atom (Br) or aryl, such as phenyl or naphthyl substituted with alkyl, alkoxy-group or halogen atom; unsubstituted hetaryl or substituted, such as thienyl-, benzothienyl-, furyl-, benzofuryl-, pyrrolyl or indolyl- wherein substitutes represent alkyl, alkoxy-, alkylthio-group, halogen atom or trifluoromethyl group; Ar means aryl, such as phenyl or naphthyl substituted with alkyl, alkoxy-group or halogen atom; unsubstituted hetaryl or substituted, such as thienyl-, benzothienyl-, furyl-, benzofuryl-, pyrrolyl or indolyl- wherein substitutes represent alkyl, alkoxy-, alkylthio-group, halogen atom or trifluoromethyl group with exception for 3,4-di-(2,5-dimethyl-3-thienyl)-1-butylmaleimide. Method involves interaction of aryl(hetaryl)boronic acid of the formula: ArB(OH)2 wherein Ar has abovementioned values with N-substituted 3,4-dibromomaleimide of the formula (III): or N-substituted 3-bromo-4-aryl(hetaryl)maleimide of the formula (IV) wherein R and Ar have abovementioned values and with using palladium catalyst in the presence of base in organic solvent medium. Also, invention to some new derivatives of 3,4-diaryl(hetaryl)maleimides that show photochrome properties.

EFFECT: improved preparing method.

7 cl, 2 dwg, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds in the family of azole-substituted spiroheterocyclic compounds, and specifically 5'-(1,3-benzothiazol-2-yl)-substituted spiro[indoline-naphthopyrans] of general formula , where R1=C1-C6 alkyl, R2=H, C1-C6 alkyl, alkoxyl, halogen.

EFFECT: compounds of formula (I) exhibit photoreversible complexing agent properties and can be used, for example, as a sensitive element of photo-controlled chemical sensors of trace amounts of ions of the zinc subgroup of metals with optical response.

2 cl, 1 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of the class spiro[chromen-4,3'-pyrrols], namely to ethyl 1'-R1-3-R2-2-amino-7,7-dimethyl-2', 5-dioxo-5'-phenyl-1',2',5',6,7,8-hexahydrospiro [chromen-4,3'-pyrrol]-4'-carboxylates of formula , where R1=CH2Ph, Ph, C6H11-c, H; R2=CN, COOMe, and to a method for producing them by reaction of 1'-R1-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrol-3-carboxylates with malononitrile or methyl cyanoacetate and dimedone in a aprotonic solvent medium.

EFFECT: production of new compounds which can be used as initial products for synthesis of new heterocyclic systems and in pharmacology as those exhibiting analgesic activity.

5 cl, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to novel cyclic N,N'-diarylthioureas or N,N'-diarylureas of general formula (1), their optic (R)- and (S)-isomers and their pharmaceutically acceptable salts - antagonists of androgenic receptors. In formula (1), where: X represents oxygen or sulfur atom; m=0 or 1, mR1 represents C1-C3alkyl; R2 and R3 represent hydrogen atom; or R2 and R3 together with carbon atom, to which they are bound, form group C=O; or represents group NH; R4 and R5 represent hydrogen atom; or R4 represents hydrogen atom, and R5 represents methyl; or R4 represents hydrogen atom, methyl, and R5 represents group Zn-Y-R6, in which n=1 or 2, Z represents CH2 or C=0 and Y- oxygen atom or N-CH3, or Y represents C=O, and Z represents CH2; R6 represents hydrogen atom, methyl, benzyl, hydroxygroup or R5 and R4 together with atoms, to which they are bound, form five or sic-member heterocycle, including, at least, oxygen or nitrogen atom, which can be substituted by methyl. Invention also relates to method of obtaining compounds.

EFFECT: invention relates to anti-cancer substance, pharmaceutical composition, medication and method of treating prostate cancer with application of invention compounds.

12 cl, 6 dwg, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) given below or pharmaceutically acceptable salts thereof:

[where: each of X, Y, Z and W independently denotes a methane group which optionally contains substitutes selected from a group of substitutes α, or a nitrogen atom (except when all elements X, Y, Z and W denote a methane group which optionally contain substitutes selected from the group of substitutes α); A denotes -(C(R3)(R4))m1-; B denotes -O-; D denotes -C(O)-; m1 equals 0; Q denotes a methane group or a nitrogen atom; R denotes a group of formula (II)

, where R6 denotes a lower alkyl group; R7 and R8, together with the nitrogen atom with which they are bonded, form a 5-6-member nitrogen-containing aliphatic heterocyclic group; and where the group of substitutes α includes the following substitutes. Group of substitutes α: halogen atom, hydroxyl group, lower alkyl group, alkoxyl group (said group can be substituted with a cycloalkyl group), amino group, mono- or disubstituted lower alkylamino group, aryl group (said group can be substituted with a halogen atom, a -SO2CH3 group), aryloxy group (said group can be substituted with a halogen atom), heteroaryl group, where 'heteroaryl group' denotes a 5- or 6-member monocyclic saturated or unsaturated group containing 1-2 heteroatoms selected from an oxygen atom or a nitrogen atom (said group can be substituted with an alkoxyl group, alkyl group). The invention also relates to a histamine 3 receptor antagonist, histamine 3 receptor inverse agonist, a prophylactic or medicinal agent, as well as a pharmaceutical composition.

EFFECT: obtaining novel biologically active compounds having histamine H3 receptor antagonist or inverse agonist action.

15 cl, 57 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula (I) or to its salt or ester in which radicals and symbols have the values presented in claim 1. These compounds are ACC inhibitors.

EFFECT: production of compounds to be applied as a therapeutic agent for various ACC-related disorders such as bacony liver, hyperlipidemia, obesity and diabetes.

13 cl, 48 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) or pharmaceutically acceptable salts thereof where R1 and R2 together denote a group selected form groups of formula (III-1): , where R9 denotes 1) a lower alkyl group, optionally substituted with a halogen atom or lower alkoxy group, 2) an aryl group, 3) an aralkyl group, 4) a heteroarylalkyl group, 5) a heteroaryl group, where the aryl, aralkyl, heteroarylalkyl and heteroaryl groups can be substituted with a halogen atom, lower alkyl group, optionally substituted with a lower alkoxy group or 1-3 halogen atoms, lower alkoxy group, optionally substituted with 1-3 halogen atoms, cyano group, hydroxy group, alkylsulphonyl group, cycloalkylsulphonyl group, aryl group, heteroaryl group, alkylaminocarbonyl group, alkanoyl amino group, alkyl amino group or dialkylamino group; R10 denotes a lower alkyl group, optionally substituted with 1-3 halogen atoms, or a lower alkylsulphonyl group; X9-X12 denotes a carbon atom or a nitrogen atom, where the carbon atom can be independently substituted with a lower alkyl group, optionally substituted with a halogen atom or a lower alkoxy group, lower alkoxy group, optionally substituted with a halogen atom, or a cyano group or a halogen atom; R3 denotes a) a group of formula (II-1): (ii-U where R4 and R5, taken together with a nitrogen atom, form a 5- or 6-member monocyclic ring, where the monocyclic ring may contain a substitute in form of a lower alkyl group, m1 equals 3; or b) a group of formula (II-2): , where R6 denotes a lower alkyl group or cycloalkyl group; m2 equals 1 or 2; X1-X4 all denote carbon atoms, or one of X1-X4 denotes a nitrogen atom and the rest denote carbon atoms; and where "heteroaryl" in each case relates to a 5- or 6-member aromatic ring containing 1-3 heteroatoms selected from a nitrogen atom, oxygen atom and a sulphur atom. The invention also relates to a histamine H3 receptor antagonist or inverse agonist, as well as a preventive or medicinal agent.

EFFECT: obtaining novel biologically active compounds, having histamine H3 receptor antagonist or inverse agonist activity.

11 cl, 8 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds -(Z)-1'-R-6',6'-dimethyl-3-(phenyl(arylamino)methylene)-6',7'-dihydro-3H-spiro[furane-2,3'-indol]-2',4,4',5(1'H,5'H)-tetraons of formula: , where Ar=phenyl, n-methoxyphenyl, n-tollyl; R=allyl, benzyl, phenyl, n-tollyl, n-methoxyphenyl, α-naphtyl, as well as to method of their obtaining, which consists in the following: isopropyl 2-(1-aryl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrol-3-yl)-2-oxoacetates are subjected to interaction with N-substituted 3-amino-5,5-dimethylcyclohex-2-enons in medium of inert aprotonic solvent with further separation of target products. Process is carried out at temperature 20-22°C. As solvent, absolute chloroform is used.

EFFECT: obtaining compounds possessing analgesic activity.

4 cl, 2 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to new compounds, and more specifically to 5-formyl-substituted indoline spirobenzopyrans with general formula 1 where R1, R2 - Alk or c-Alk; R3 -CHO or NO2 group (electron-acceptor substitute), with photochromic properties. The invention also relates to the method of producing 5-formyl substituted derivatives of indoline spirobenzopyrans with formula 1. Spirobenzopyrans, which have electron-acceptor substitutes in the pyran part of the molecule, are subjected to direct selective formylation in position 5 in a trifluoroacetic acid medium with urotropine (hexamethylenetetramine) at boiling point of the mixture in an inert atmosphere for 1-1.5 hours. The obtained 5-formyl-substituted spirobenzopyrans are photochromic compounds are photochromic and can be used for making new photochromic materials (recording devices or information storage; photo-switching activity of biological objects and polymer matrices, complex formation; information security media, maps, special document protection equipment) or as advanced initial compounds for further synthesis of a large number of new photochromic objects.

EFFECT: wider field of application of the compounds.

2 cl, 1 tbl, 3 ex

FIELD: chemistry, pharmaceuticals.

SUBSTANCE: invention pertains to new compounds with formula I, their pharmaceutical salts and to complex esters. The invented compounds have inhibiting propertied towards catepsin K and can be used for making medicinal preparations for curing diseases and conditions, in which catepsin K is involved, for example, inflammation, rheumatoid arthritis, osteoarthritis, osteoporosis and tumorous diseases. In general formula I R represents H, R13 represents (inferior)alkyl, C3-C10cylcloalkyl or C3-C10cycloalkyl(inferior)alkyl, each of which is independently optionally substituted with a halogen atom, hydroxyl, CN, NO2 or optionally mono- or di(inferior)alkyl substituted amino group; and R14 represents H or optionally substituted phenyl, phenyl-W-, phenyl(inferior)alkyl-W-, C3-C10cycloalkyl, C3-C10cycloalkyl-W-, N-heterocyclyl, N-heterocyclyl -W-. Substitutes of the indicated values of radicals are shown in the formula of invention. The invention also relates to methods of obtaining the compounds.

EFFECT: obtaining pyrrolopyrimidines with inhibiting properties towards catepsin K, which can be used for making medicinal preparations for curing diseases and conditions, in which catepsin K is involved.

4 cl, 59 tbl, 10 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of derivatives of indolinospiropyrane of the formula (1): wherein R1 means (C1-C18)-alkyl; each among R2 and R3 mean independently (C1-C4)-alkyl; R4 means hydrogen atom, hydroxy-group, trichloromethyl, trifluoromethyl formyl, (C1-C)-alkyl, halogen atom, (C1-C4)-alkoxy-, nitro-group; x = 1 or 2. Method comprises the following steps: (i) synthesis of indoline on polymeric carrier of the formula (III): wherein R1 means (C1-C18)-alkyl; each among R2 and R means independently (C1-C4)-alkyl; (ii) treatment of indoline-carrying polymeric carrier wherein this carrier represents hydroxy-resin at temperature from 50°C to 120°C in inert atmosphere for time from 14 h to 11 days with a derivative of salicylic aldehyde of the formula (VI): wherein R4 means hydrogen atom, hydroxy-group, trichloromethyl, trifluoromethyl, formyl, (C1-C4)-alkyl, halogen atom, (C1-C4)-alkoxy-, nitro-group; x = 1 or 2 to yield indolinospiropyrane compound of the formula (I), and (iii) release of indolinospiropyrane compound of the formula (I). Invention proves synthesis of novel derivatives of indolinospiropyrane possessing photochromic properties.

EFFECT: improved method of synthesis.

8 cl, 28 ex

FIELD: pharmaceutical chemistry, in particular pharmaceutical compositions.

SUBSTANCE: new spyro(2H-1-benzopyrane-2,4'-piperidine) derivatives of general formula I

and pharmaceutically acceptable salts thereof are disclosed. In formula dotted line is optional bond; Y is 1-4 substituents independently selected from hydrogen, halogen, C1-C4-alkyl, optionally substituted with one or more halogen, C1-C6-alkyloxy, optionally substituted with halogen or C3-C6-cycloalkyl, C2-C6-alkenyloxy, C2-C6-alkinyloxy, C3-C6-cycloalkyloxy, C6-C12-aryloxy, arylalkyloxy, pyridilmethoxy, SR3, NR3R4, OSO2R5, and NR3SO2R4; or two Y together may form O-(CH2)n-O or O-(CF2)n-O, wherein n is 1 or 2: or Y is condensed C5-C6-aryl group; X is 1-3 substituents independently selected from hydrogen, halogen, hydroxyl, C1-C6-alkoxy, and C1-C4-alkyl; R1 is hydrogen, C1-C4-alkyl, or C6-C12-aryl; R2, R3, and R4 are independently hydrogen or C1-C4-alkyl; R5 is C6-C12-aryl. Also disclosed are pharmaceutical compositions including said derivatives and having activity in relation to CNS.

EFFECT: new compounds with valuable pharmacological action.

9 cl, 1 tbl, 83 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention proposes derivative of 3,4-dihydroisoquinoline of the formula (I) or its nontoxic salt and a pharmaceutical agent comprising its as an active component (wherein all symbols have the same values as given in description). Compound of the formula (I) possesses agonistic effect on CB2-receptors and, therefore, it can be used for prophylaxis and/or treatment of different diseases, for example, asthma, nasal allergy, atopic dermatitis, autoimmune diseases, rheumatic arthritis, immune dysfunction, postoperative pain and carcinomatous pain.

EFFECT: valuable medicinal properties of derivatives.

14 cl, 33 tbl, 561 ex

FIELD: organic chemistry.

SUBSTANCE: invention describes C2-phenyl-substituted cyclic ketoenols of the general formula: wherein W means hydrogen atom, alkyl with 1-6 carbon atoms; X means alkyl with 1-6 carbon atoms, alkenyl with 2-6 carbon atoms; Y means hydrogen atom, methyl, ethyl, isopropyl, alkenyl with 2-6 carbon atoms, ethynyl; Z means hydrogen atom, alkyl with 1-6 carbon atoms under condition that at least one of residues W, X, Y or Z means a chain with at least 2 carbon atoms but only one of residues X and Y can mean alkenyl with 2-6 carbon atoms; CKE means one of the following groups: , , and wherein A means hydrogen atom, alkyl with 1-6 carbon atoms; B means hydrogen atom, alkyl with 1-6 carbon atoms; A and B in common with carbon atom to which they are bound mean cycloalkyl with 5-6 carbon atoms wherein the ring carbon atom can be substituted with oxygen atom and can be substituted with alkyl with 1-6 carbon atoms or alkoxyl with 1-6 carbon atoms; A and B in common mean group of the formula: D means hydrogen atom or phenyl substituted with fluorine atom if CKE means group of the formula (4); G means hydrogen atom (a) or one of groups of the formula: or wherein R1 means alkyl with 1-6 carbon atoms, alkoxymethyl with 1-2 carbon atoms; R2 means alkyl with 1-4 carbon atoms; A and Q1 in common mean alkanediyl with 3-4 carbon atoms; Q2 means hydrogen atom. Invention provides preparing compound of the formula (I) possessing with insecticide, acaricide and herbicide activity.

EFFECT: valuable properties of compounds.

2 cl, 8 tbl, 32 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of derivatives of indolinospiropyrane of the formula (1): wherein R1 means (C1-C18)-alkyl; each among R2 and R3 mean independently (C1-C4)-alkyl; R4 means hydrogen atom, hydroxy-group, trichloromethyl, trifluoromethyl formyl, (C1-C)-alkyl, halogen atom, (C1-C4)-alkoxy-, nitro-group; x = 1 or 2. Method comprises the following steps: (i) synthesis of indoline on polymeric carrier of the formula (III): wherein R1 means (C1-C18)-alkyl; each among R2 and R means independently (C1-C4)-alkyl; (ii) treatment of indoline-carrying polymeric carrier wherein this carrier represents hydroxy-resin at temperature from 50°C to 120°C in inert atmosphere for time from 14 h to 11 days with a derivative of salicylic aldehyde of the formula (VI): wherein R4 means hydrogen atom, hydroxy-group, trichloromethyl, trifluoromethyl, formyl, (C1-C4)-alkyl, halogen atom, (C1-C4)-alkoxy-, nitro-group; x = 1 or 2 to yield indolinospiropyrane compound of the formula (I), and (iii) release of indolinospiropyrane compound of the formula (I). Invention proves synthesis of novel derivatives of indolinospiropyrane possessing photochromic properties.

EFFECT: improved method of synthesis.

8 cl, 28 ex

FIELD: chemistry, pharmaceuticals.

SUBSTANCE: invention pertains to new compounds with formula I, their pharmaceutical salts and to complex esters. The invented compounds have inhibiting propertied towards catepsin K and can be used for making medicinal preparations for curing diseases and conditions, in which catepsin K is involved, for example, inflammation, rheumatoid arthritis, osteoarthritis, osteoporosis and tumorous diseases. In general formula I R represents H, R13 represents (inferior)alkyl, C3-C10cylcloalkyl or C3-C10cycloalkyl(inferior)alkyl, each of which is independently optionally substituted with a halogen atom, hydroxyl, CN, NO2 or optionally mono- or di(inferior)alkyl substituted amino group; and R14 represents H or optionally substituted phenyl, phenyl-W-, phenyl(inferior)alkyl-W-, C3-C10cycloalkyl, C3-C10cycloalkyl-W-, N-heterocyclyl, N-heterocyclyl -W-. Substitutes of the indicated values of radicals are shown in the formula of invention. The invention also relates to methods of obtaining the compounds.

EFFECT: obtaining pyrrolopyrimidines with inhibiting properties towards catepsin K, which can be used for making medicinal preparations for curing diseases and conditions, in which catepsin K is involved.

4 cl, 59 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to new compounds, and more specifically to 5-formyl-substituted indoline spirobenzopyrans with general formula 1 where R1, R2 - Alk or c-Alk; R3 -CHO or NO2 group (electron-acceptor substitute), with photochromic properties. The invention also relates to the method of producing 5-formyl substituted derivatives of indoline spirobenzopyrans with formula 1. Spirobenzopyrans, which have electron-acceptor substitutes in the pyran part of the molecule, are subjected to direct selective formylation in position 5 in a trifluoroacetic acid medium with urotropine (hexamethylenetetramine) at boiling point of the mixture in an inert atmosphere for 1-1.5 hours. The obtained 5-formyl-substituted spirobenzopyrans are photochromic compounds are photochromic and can be used for making new photochromic materials (recording devices or information storage; photo-switching activity of biological objects and polymer matrices, complex formation; information security media, maps, special document protection equipment) or as advanced initial compounds for further synthesis of a large number of new photochromic objects.

EFFECT: wider field of application of the compounds.

2 cl, 1 tbl, 3 ex

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