The way to obtain 7-bromo-1,3-dihydro-5-/2-chlorophenyl/-2h-1,4 - benzodiazepin-2-it, the intermediate compound 5-bromo-2-/2 - chloracetamide/-2'-chlorobenzophenone

The invention relates to 1,3-cyclohexandione, as well as a means of protection of plants, particularly to herbicide compositions and method of controlling undesirable vegetation

Invention concerns new photoinitiators, method of their obtainment, compositions hardening with irradiation, and application of those compositions in coating preparation. Invention claims photoinitiators of formulae I , where R₁, R₂, R₃ and R₄ are independently C₁-C₈alkyl or benzyl; or R₁ and R₂ together and/or R₃ andR₄ together are cyclohexyl; R₅ is hydrogen; A is OH, Br, -O-C₁-C₁₂alkyl, -O-R₇, where R₇ is linear or forked C₂-C₂₁hydroxyalkyl carbon chain interrupted by 1 to 9 oxygen atoms; or -NR₈R₉, where R₈ and R₉ are independently C₁-C₂₁alkyl or C₂-C₄alkyl substituted by one or more OH groups; A' is -O-; X and Y are independently -OH or -N(CH₃)₂; n is 2; R₆ is linear or forked divalent -CO-NH-(C₂-C₁₆alkylene)-(NH-CO)- radical or linear or forked -CO-NH-(C₀-C₉alkylene)-(NH-CO)- which can be interrupted by phenylene, or linear or forked divalent -C₂-C₅₀alkylene radical with carbon chain interrupted by 1 to 15 oxygen atoms.

Invention relates to novel biologically active compounds of formula , where substitutes R, R¹, R² and R³ are defined in the formula of invention, and can be obtained using a method which involves reaction of corresponding chloroacetamides with a prepared solution of elementary sulphur with morpholine or piperidine, passing the obtained solution of monothiooxamides through a layer of sorbent and then reaction of monothiooxamides with hydrazine-hydrate, reaction of the obtained compound with aldehydes in dimethyl formamide at room temperature and precipitation with methanol which gives good output of the end product.

Claimed invention relates to novel compounds of general formula (A), their stereoisomers or pharmaceutically acceptable salts, possessing ability to inhibit activity of isomerase, taking part in visual cycle. Compounds can be applied for treatment of ophthalmological disease or disorder, such as age-related macular degeneration or Stargardt's macular dystrophy. In general formula (A) Z represents-C(R⁹)(R¹⁰)-C(R¹)(R²)-; R¹ and R² each, independently on each other, are selected from hydrogen, halogen, C₁-C₅alkyl, or -OR⁶; or R¹ and R² together from oxo; R³ and R⁴ each, independently on each other, are selected from hydrogen; R⁶ is selected from a) C₅-C₁₅alkyl, optionally substituted with hydroxy, C₁-C₈alkoxy; or b) C₅-C₁₀carbocyclylalkyl, in which carbocycle is 4-, 5-, 6-, 7- or 8-member non-aromatic carbocycle, optionally substituted with hydroxy, halogen or R⁶CO₂-; R⁹ and R¹⁰ each, independently on each other, is selected from hydrogen, halogen, C₁-C₅alkyl, optionally substituted with hydroxy, or -OR¹⁹; or R⁹ and R¹⁰ form oxo; or optionally, R⁹ and R¹ together form direct bond to provide double bond; or optionally, R⁹ and R¹ together form direct bond, and R¹⁰ and R² together form direct bond to provide triple bond; R¹¹ and R¹² each, independently on each other, is selected from hydrogen, -C(=O)R²³ or -C(NH)NH₂, R²³ is selected from C₁-C₈alkyl; R⁶, R¹⁹ and R³⁴ are independently on each other are hydrogen or C₁-C₈alkyl; each R³³ is independently selected from halogen, hydroxyl, C₁-C₅carboalkoxy, C₁-C₈alkyl, optionally substituted with hydroxy; and n equals 0 or 1.

Invention proposes new compounds of the general formula (I):

Invention relates to synthesis of camptotecin analogues from 2'-amino-5'-hydroxypropiophnone corresponding to AB ring portion of camptotecin structure and tricyclic ketone converted into CDE ring portion in camptotecin structure. Preparation of 2'-amino-5'-hydroxypropiophnone comprises following steps: (1) preparing compound (b) by mixing compound (a), benzylation agent, and a base followed by stirring mixture obtained in solvent on heating under reflux; (2) preparing compound (c) by dropwise adding Grignard reagent to compound (b) under an inert gas atmosphere; (3) preparing compound (d) by mixing compound (c) with an oxidant and stirring resulting mixture; and (4) preparing compound (e) via catalytic reduction of compound (d) (see scheme 1 below). Intermediate compounds (c') and (d') are described. Also described is a method for preparing tricyclic ketone to provide efficient complete synthesis of camptotecin serving as starting compound for irinotecan hydrochloride and a various types of camptotecin derivatives as well as for stable preparation of camptotecin and its derivatives. Scheme 1: .

Invention concerns new photoinitiators, method of their obtainment, compositions hardening with irradiation, and application of those compositions in coating preparation. Invention claims photoinitiators of formulae I , where R₁, R₂, R₃ and R₄ are independently C₁-C₈alkyl or benzyl; or R₁ and R₂ together and/or R₃ andR₄ together are cyclohexyl; R₅ is hydrogen; A is OH, Br, -O-C₁-C₁₂alkyl, -O-R₇, where R₇ is linear or forked C₂-C₂₁hydroxyalkyl carbon chain interrupted by 1 to 9 oxygen atoms; or -NR₈R₉, where R₈ and R₉ are independently C₁-C₂₁alkyl or C₂-C₄alkyl substituted by one or more OH groups; A' is -O-; X and Y are independently -OH or -N(CH₃)₂; n is 2; R₆ is linear or forked divalent -CO-NH-(C₂-C₁₆alkylene)-(NH-CO)- radical or linear or forked -CO-NH-(C₀-C₉alkylene)-(NH-CO)- which can be interrupted by phenylene, or linear or forked divalent -C₂-C₅₀alkylene radical with carbon chain interrupted by 1 to 15 oxygen atoms.

Invention relates to novel nonsteroid synthetic derivatives with the following structures or their pharmaceutically acceptable salts:

Invention relates to field of organic chemistry, to derivatives of 1,4-diketones, namely to novel biologically active substance -2-(2,4-dichloranilino)-1,4-bis(4-methylphenyl)-2-buten-1,4-dione of formula 1 , which possesses antimicrobial activity and can be applied in medicine.

In the compound of general formula R₁ represents halogen, C_1-4alkyl, or C_1-4alkoxy; R₂ represents hydrogen, halogen; R₃ represents hydrogen, or one or several halogens; R₄ represents hydrogen, halogen, R₈ or Y₁R₈; Y₁ represents -NR_a-; R_a and R_b are similar or different, and each represents hydrogen or C_1-4alkyl; R₈ represents hydrogen, C_1-10alkyl; R₇ represents hydrogen, hydroxy, trifluoromethyl, amino, C_1-6hydroxyalkyl, C_1-4alkoxy, C_1-4alkylthio, C_1-6alkylamino, C_1-4alkoxycarbonyl, -S(O)₂R, -COOH, -CONH₂, or -NR_aC(O)R', where R and R' are similar or different, and each represents hydrogen or C_1-3alkyl; R₅ represents -COOH, Y₂R₉, Y₂R₉Y₃R₁₀, C_1-6alkyl-Y₂R₉, C_1-10alkyl, or unsaturated C_3-8carbocycle, said R₅ is substituted with one or several, similar or different substituents, represented by R₇; R₆ represents hydrogen; Y₂ represents -O-, -NR_a-, -NR_aC(O)NR_b-, -NR_aC(O)-, -C(O)NR_a-, -C(O)-, -NR_aC(O)O-, or -OC(O)-; R₉ represents C_1-10alkyldioxolanyl, C_1-10alkylthiazolyl, C_1-10alkylmorpholinyl, etc.

Invention relates to an improved method of co-production of 3,3'-dinitro-4,4'-bis(N,N-dimethylamino)benzophenone and 3,3'-dinitro-4-hydroxy-4'-(N,N-dimethylamino)benzophenone. The method includes processing 3,3'-dinitro-4,4'-dichlorobenzophenone in N,N-dimethylformamide or N,N-dimethylacetamide with hydroxides of alkali metals in the form of 20-50% water solution at a temperature of 30-60°C and a molar ratio 3,3'-dinitro-4,4'-dichlorobenzophenone:NaOH (KOH):DMFA (DMAA)= 1:4÷10:20÷30.

Invention relates to a method of producing N-[5-(3-dimethylamino-acryloyl)-2-fluorophenyl]-N-methylacetamide of formula (I). The method is realised by reacting N-(5-acetyl-2-fluorophenyl)-N-methylacetamide of formula (VI) with excess N,N-dimethylformamide dimethylacetal (NNDMF-DMA) in the presence of a nonpolar solvent at temperature of 70-90°C. The invention discloses a method of producing a N-{2-fluoro-5-[3-(thiophene)-2-carbonyl-pyrazolo[1,5-a]pyrimidin-7-yl]phenyl}-N-methylacetamide compound of formula (II), which involves methylation of N-(5-acetyl-2-fluorophenyl)-acetamide at temperature of 15-50°C, reacting the obtained compound of formula (VI) with NNDMF-DMA, and reacting the obtained compound of formula (I) with (5-amino-1H-pyrazol-4-yl)thiophen-2-yl-methanone in glacial acetic acid at temperature of 60-90°C in the presence of an aliphatic alcohol. The invention also relates to an intermediate compound of formula (VI).

Stabilising composition is described, containing (A) compound of 2,4-bis-(4-phenylphenyl)-6-(2-hydroxyphenyl)-1,3,5-triazine series by formula (I), and (B) one or more compounds chosen from group, which include benzotriazoles by formula (IIa), 2-hydroxybenzophenones by formula (IIb), oxanilides by formula (IIc), 2-hydroxyphenyltriazines by formula (IId), cinnamates by formula (IIe), and benzoates by formula (IIf). There are also described: composition, containing stabiliser composition and organic material; method for organic material stabilisation; and application of stabiliser composition to organic material stabilisation.

Invention concerns new photoinitiators, method of their obtainment, compositions hardening with irradiation, and application of those compositions in coating preparation. Invention claims photoinitiators of formulae I , where R₁, R₂, R₃ and R₄ are independently C₁-C₈alkyl or benzyl; or R₁ and R₂ together and/or R₃ andR₄ together are cyclohexyl; R₅ is hydrogen; A is OH, Br, -O-C₁-C₁₂alkyl, -O-R₇, where R₇ is linear or forked C₂-C₂₁hydroxyalkyl carbon chain interrupted by 1 to 9 oxygen atoms; or -NR₈R₉, where R₈ and R₉ are independently C₁-C₂₁alkyl or C₂-C₄alkyl substituted by one or more OH groups; A' is -O-; X and Y are independently -OH or -N(CH₃)₂; n is 2; R₆ is linear or forked divalent -CO-NH-(C₂-C₁₆alkylene)-(NH-CO)- radical or linear or forked -CO-NH-(C₀-C₉alkylene)-(NH-CO)- which can be interrupted by phenylene, or linear or forked divalent -C₂-C₅₀alkylene radical with carbon chain interrupted by 1 to 15 oxygen atoms.

Invention refers to production method of 1-(4-chlorophenyl)-2-cyclopropylpropane-1-one being a by-product for making biologically active substances, as well as to production method for 1-(4-chlorophenyl)-2-methyl-3-butene-1-one being a by-product for making 1-(4-chlorophenyl)-2-cyclopropylpropane-1-one. Production method for 1-(4-chlorophenyl)-2-cyclopropylpropane-1-one consists that 4-chlorobenzonitrile reacts with crotyl chloride or bromide and zinc in organic solvent and optionally with aluminium chloride. Hydrolysis of reaction mixture 2M with hydrochloric acid results in separation 1-(4-chlorophenyl)-2-methyl-3-butene-1-one thereafter purified. It reacts dibromomethane, zinc and copper monochloride in organic solvent with catalyst added or in ultrasonic bath. It is followed with separation of end product by common method.

M-chlorobenzophenone is used as an intermediate product in synthesis of original anticonvulsant "halodif" (m-chlorobenzhydrylurea). The method involves diazotisation of 2-amino-5-chlorobenzophenone at room temperature using p-toluenesulfonic acid and polymer diazotising agent, with subsequent treatment of the obtained diazonium tosylate with an aqueous solution of sodium hypophosphite.

Present invention relates to a method for synthesis of 4,4'-difluorobenzophenone, the main raw product for synthesis of aromatic polyester-ketones. The method involves a first step where fluorobenzene reacts with formaldehyde under conditions for catalysis with organic sulphonic acids to form difluorodiphenylmethane. The product is extracted and oxidised with nitric acid at the second step to 4,4'-difluorobenzophenone.

Present invention relates to a method of producing fluorine-containing tetraketones of general formula: , where I) R₁=CHCH(CH₃)₂; R₂=CH₃; II)R₁=CH₂; R₂=Ph III) R₁=CHCH₂CH₃; R₂=Ph, which can be used as synthons for producing their fluorine-containing aza- and thio-analogues, β-hydroxyketones, pyrazoles, isoxazoles, as well as biologically active substances. The method involves reacting a diester of perfluoro-dicarboxylic acid with an alkylketone in the presence of sodium hydride in the medium of an organic solvent. The diester of perfluoro-dicarboxylic acid used is dimethyl ester of perfluoro-dodecane dicarboxylic acid and the alkylketone used is: acetophenone, methyl isobutyl ketone or propyl phenyl ketone, and the process is carried out in the presence of a catalyst - dibenzo-24-crown-8 ester, in molar ratio diester of perfluoro-dicarboxylic acid: alkylketone: sodium hydride: catalyst equal to 1 : (2-3.5) : 1 : (0.00025-0.0005).

Invention relates to an improved method of producing a compound of formula , where Z is optionally substituted phenyl and Q is phenyl or 1-naphthalenyl, each optionally substituted. The method involves distillation of water from a mixture containing a compound of formula , a compound of formula , a base containing at least one compound selected from a group comprising alkali-earth metal hydroxides of formula 4 M(OH)₂, where M is Ca, Sr or Ba, alkali metal carbonates of formula 4a (M¹)₂CO₃ , where M¹ is Li, Na or K, 1,5-diazabicyclo[4,3.0]non-5-ene and 1,8-diazabicyclo[5.4.0]undec-7-ene, and an aprotic solvent capable of forming a low-boiling azeotrope with water. The invention also relates to a method of producing a compound of formula 2, a method of producing a compound of formula from a compound of formula 1 and a compound of formula 2.

Meta-chlorobenzophenone is obtained by diazotization of 2-amino-5-chlorobenzophenone at room temperature. Diazotization is carried out in mixture of icy acetic and hydrochloric acids with application of water solution of sodium nitrate with the following processing of obtained salt of diazonium with water solution of sodium hypophosphite or copper protoxide in ethyl alcohol for 0.5-1 h.