The method of obtaining n(d)ribitil-3,4-xylidine
(57) Abstract:The invention relates to the field of organic chemistry and relates to the process of obtaining intermediate for the synthesis of vitamin B2. N(D)-ribitil-3,4-xylidine get recovery by condensation of equimolar amounts of D-ribose derivative 3,4-xylene General formula
< / BR>under pressure, in the presence of a catalyst. In the claimed method of obtaining N(D)-ribitil-3,4-xylidine process is carried out in continuous mode, using a stationary catalyst based on metals of group VIII. The original connection serves Autonomous parallel streams into the reaction zone at a constant bubbling of hydrogen. table 1. 1 Il. The invention relates to the field of organic chemistry and relates to the process of obtaining intermediate for the synthesis of vitamin B2.N(D)-ribitil-3,4-xylidine (I) receive reductive condensation of D-ribose (II) with 3,4-dimethylaniline (IIIa) in the presence of equimolar amount of boric acid in the periodic conditions:
< / BR>The yield of the final product 1 is 75 78% (U.S. patent N 2429244, NCI 260 211, 1947).The disadvantage of this method is that after the end of the reaction product 1 must otmyvochnaja 1 reductive condensation of water-methanol solution II and IIIa in the autoclave (U.S. patent N 2477560, NCI 260 211, 1946). A hydrogen pressure of 2.5 5.0 MPa, temperature 35 75oC, the Nickel catalyst is skeletal.The disadvantage of this method is the use of pyrophoric Nickel catalyst and carrying out the process at relatively high pressures.The closest in technical essence is a method of obtaining 1 reductive condensation of the methanol solutions II and IIIa (or 3,4-dimethylnitrobenzene (IIIB) in the autoclave. The process is conducted under a hydrogen pressure of 0.1 to 5.0 MPa at a temperature of 40 80oC for 120 min with addition and without addition of catalytic amounts of boric acid, the catalyst is Ni-skeletal. The yield of the target product I is to 88.7 89.9 percent (with H3BO4) and 34.8 40.6 per cent (without H3BO4) (Offenlegungsschrift DE 3615834, MKI4C 07 91/10, 1987).The method is not effective enough because of the use of homogeneous additive (H3BO4) and use of pyrophoric skeletal catalyst.The basis of the invention is a continuous method of obtaining N(D)-ribitil-3,4-xylidine.The technical result consists in the intensification of synthesis and increasing the selectivity of the process due to the fact that the reduction Conde the result is achieved by a method for obtaining N(D)-ribitil-3,4-xylidine carry out the reaction of the reductive condensation of equimolar amounts of D-ribose derivative 3,4-xylene General formula
< / BR>under pressure, in the presence of a catalyst, and a continuous process carried out on a stationary catalyst, the source connection serves Autonomous parallel streams into the reaction zone at a constant bubbling of hydrogen.A special feature of this process obtain N(D)-ribitil-3,4-xylidine is that the use of heterogeneous catalysts for hydrogenation, which represents a transition metal of group VIII deposited on the granules of media that allows the reaction in a continuous conditions, homogeneous without additives, using both amino-and nitro-derivatives of 3,4-xylene.Compared with the prototype method for producing N(D)-ribitil-3,4-xylidine is continuous, the original connection serves Autonomous parallel streams into the reaction zone and the process is carried out at constant bubbling of hydrogen.A positive result of the proposed method is to obtain the target product with a yield of 75 to 85%
The drawing shows a breadboard is hydrated catalyst 2. In the lower part of the reactor 1 are carts flows source products: P1
a solution of D-ribose, P2 solution of one of the derivatives of 3,4-xylene and P3
the hydrogen. In the upper part of the reactor 1 are: A4 exit of the reaction mixture containing N(D)-ribitil-3,4-xylidine and P5 sparging hydrogen.The synthesis is carried out in an isothermal reactor 1 continuous action, which is filled heterogeneous granular hydrogenation catalyst 2, which represents a transition metal of group VIII on a carrier. In the lower part of the reactor 1 serves: aqueous solution of D-ribose (P1), the solution of one of the derivatives of 3,4-xylene (P2) and hydrogen (P3) under pressure. The process is carried out at a temperature of 70 90oC, hydrogen pressure of 0.5 to 2.0 MPa, the load on the catalyst 0,6710-42,2010-4the Mols-1kg-1, the bubbling of hydrogen at the reactor exit 0,110-61,210-6m3/c (P5).Example 1. The reactor 1 is filled granular catalyst Pd/Sibunit (2% Pd). In the lower part of the reactor received: aqueous solution of D-ribose with a speed of 310-6mol/s, a solution of 3,4-dimethylnitrobenzene in isopropanol with a speed of 3 to 10-6mol/C and hydrogen pressure of 2 MPa; the load on the catalyst sostav-6m3/C. the Content of the target product 88.4% of
Example 2. The reactor 1 is filled granular catalyst Pd/Sibunit (2% Pd). In the lower part of the reactor received: aqueous solution of D-ribose with the speed of 910-6mol/s, a solution of 3,4-dimethylaniline in isopropanol with the speed of 910-6mol/C and hydrogen pressure of 2 MPa; the load on the catalyst is 2,2010-4the Mols-1kg-1; temperature 85oC; the bubbling of hydrogen at the reactor exit 1,410-6m3/C. the Content of the target product 87,4%
Example 3. The reactor 1 is filled granular catalyst Ni/Al2O3(16% Ni). In the lower part of the reactor received: aqueous solution of D-ribose with a speed of 310-6mol/s, a solution of 3,4-dimethylaniline in ethanol with a speed of 310-6mol/C and hydrogen pressure of 2 MPa; the load on the catalyst is 1,010-4the Mols-1kg-1; temperature 80oC; the bubbling of hydrogen at the reactor exit 0,410-6m3/C. the Content of the target product of 85.2%
The results of several experiments are shown in the table. The method of obtaining N(D)-ribitil-3,4-xylidine, including reductive condensation of equimolar amounts of D-ribose derivative 3,4-xylene total f is, the source connection is served in the reaction zone of Autonomous concurrent threads with constant bubbling of hydrogen and the process is performed on a stationary catalyst in a continuous mode.
R-NH-CO-NH-NH2(I) where R = D-glucosyl-D-galactosyl-L-arabinosyl-that can be used for the synthesis of compounds possessing anti-inflammatory, antimicrobial activity
FIELD: pharmaceutical technology.
SUBSTANCE: invention relates to the improved sucralose formulation and a method for its crystallization. Method involves controlling pH value of solution in the range from about 5.5 to about 8.5 in the process of formation of sucralose crystals. Invention provides the development of the improved composition comprising crystalline sucralose and possessing the enhanced stability.
EFFECT: improved preparing method, improved properties of composition.
24 cl, 4 tbl, 4 ex
FIELD: organic chemistry, chemical technology.
SUBSTANCE: invention relates to an improved solid-phase method for synthesis of radioisotope indicators, in particular, for synthesis of compounds labeled with 18F that can be used as radioactive indicators for positron- emission tomography (PET). In particular, invention relates to a method for synthesis of indicator labeled with 18F that involves treatment of a precursor fixed on resin if the formula (I): SOLID CARRIER-LINKER-X-INDICATOR wherein X means a group promoting to nucleophilic substitution by a definite center of a fixed INDICATOR with 18F- ion for preparing a labeled indicator of the formula (II): 18F-INDICATOR; to compound of the formula (Ib):
and compound of the formula (Ih): ;
to radiopharmaceutical set of reagents for preparing indicator labeled with 18F for using in PET; to a cartridge for radiopharmaceutical set of reagents for preparing indicator labeled with 18F for using in positron-emission tomography.
EFFECT: improved method of synthesis.
13 cl, 1 sch, 3 ex
SUBSTANCE: developed method of sucralose production using acyl-sucralose implies (a) adjustment of pH factor of specified supplied mixture to value ranged from 8.0 to 12.0 by alkali metal hydroxide addition; (b) buffer addition to specified base mixture in amount enough for specified pH factor stabilization within stated range over holding stage (c); (c) holding of specified base mixture at appropriate temperature over time period enough for effective transformation of specified acyl-sucralose compound into free sucralose; (d) reduction of specified pH factor of specified base mixture up to value from 4 to 8; (e) sucralose release from product of step (d) resulted thereby in released sucralose.
EFFECT: improved method of water deacylation procedure stabilization.
22 cl, 1 tbl, 1 ex
SUBSTANCE: invention concerns a variant of admixture extraction from composition containing extraneous matter and sucralose, which is used as a sweetener. One of the variants includes following stages: (a) first solvent extraction of the said composition containing sucralose and admixtures in the first solvent with the help of another solvent, at least partially immiscible, in order to remove admixtures to the said second solvent; (b) second solvent extraction of the said composition containing sucralose and admixtures in the first solvent with the help of the third solvent, at least partially immiscible, in order to transfer sucralose to the said third solvent; where stage (a) removes at least a part of admixtures to the second solvent; and stage (b) transports most of sucralose to the third solvent and detains most of admixtures in the first solvent.
EFFECT: efficient removal of admixtures from compositions.
34 cl, 4 tbl, 2 dwg, 2 ex
SUBSTANCE: in method of obtaining compound aminoalkyl glucosaminide 4-phosphate of formula , X represents , Y represents -O- or NH-; R1, R2 and R3, each is independently selected from hydrogen and saturated and unsaturated (C2-C24) aliphatic acyl groups; R8 represents -H or -PO3R11R11a, where R11a and R11a, each is independently -H or (C1-C4) aliphatic groups; R9 represents -H, -CH3 or -PO3R13aR14, where R13a and R14, each is independently selected from -H and (C1-C4) aliphatic groups, and where indices n, m, p, q each independently is a integer from 0 to 6 and r is independently integer from 2 to 10; R4 and R5 are independently selected from H and methyl; R6 and R7 are independently selected from H, OH, (C1-C4) oxyaliphatic groups -PO3H2, -OPO3H2, -SO3H, -OSO3H, -NR15R16, -SR15, -CN, -NO2, -CHO, -CO2R15, -CONR15R16, -PO3R15R16, -OPO3R15R16, -SO3R15 and -OSO3R15, where R15 and R16, each is independently selected from H and (C1-C4) aliphatic groups, where aliphatic groups are optionally substituted with aryl; and Z represents -O- or -S-; on condition that one of R8 and R9 represents phosphorus-containing group, but R8 and R9 cannot be simultaneously phosphorus-containing group, including: (a) selective 6-O- silylation of derivative of 2-amino-2-desoxy-β-D-glucopyranose of formula , where X represents O or S; and PG independently represent protecting group, which forms ester, ether or carbonate with oxygen atom of hydroxy group or which forms amide or carbamate with amino group nitrogen atom, respectively; by means of tri-substituted chlorosilane RaRbRcSi-Cl, where Ra, Rb and Rc are independently selected from group, consisting of C1-C6alkyl C3-C6cycloalkyl and optionally substituted phenyl, in presence of tertiary amin, which gives 6-silylated derivative; (b) selective acylation of 4-OH position of obtained 6-O-silylated derivative with 6-3-alkanoyloxyalcanoic acid or hydroxyl-protected (R)-3-hydroxyalkanoic acid presence of a carbodiimide reagent and catalytic 4-dimethylaminopyridine or 4-pyrrolidinopyridine to give a 4-O-acylated derivative; (c) selectively deprotecting the nitrogen protecting groups, sequentially or simultaneously and N,N-diacylating the resulting diamine with (R)-3-alkanoyloxyalkanoic acid or a hydroxy-protected (R)-3-hydroxyalkanoic acid in presence of peptide condensation reagent; (d) introducing a protecting phosphate group at 3-position with a chlorophosphate or phosphoramidite reagent to give a phosphotriester; and (e) simultaneous or sequential deprotecting phosphate, silyl, and remaining protecting groups.
EFFECT: method improvement.
11 cl, 3 ex
SUBSTANCE: invention claims derivatives of 1-α-halogen-2,2-difluoro-2-deoxy-D-ribofuranose of the general formula (I) in solid state, where R1 is benzoyl or ; R2 is hydrogen; and X is CI, Br or I; which can be applied as intermediates in stereoselective method of gemcitabine obtainment. In addition, invention claims stereoselective method of obtaining compounds of the general formula (I), including stages of: (i) recovery of 1-oxoribose of formula to obtain lactol of formula ; (ii) interaction of compound of formula (III) with halogen phosphate compound of formula in the presence of a base to obtain 1-phosphatefuranose derivative of formula ; and (iii) interaction of compound of formula (V) (also included in the claim) with halogen source, with further recrystallisation of obtained product; where R1, R2 and X are the same as indicated above while R3 is phenyl.
EFFECT: efficient method of obtaining derivatives of the abovementioned agent.
11 cl, 6 ex
SUBSTANCE: invention refers to synthesis of [18F]fluororganic compounds ensured by reaction of [18F]fluoride and relevant halogenide or sulphonate with alcoholic vehicle of formula 1 where R1, R2 and R3 represent hydrogen atom or C1-C18 alkyl.
EFFECT: possibility for mild process with low reaction time and high yield.
21 cl, 2 tbl, 27 ex
SUBSTANCE: invention relates to a method of producing a protected fluorinated glucose derivative, involving reaction of a tetraacetylmannose derivative with a fluoride, distinguished by that the reaction is carried out in a solvent which contains water in amount of more than 1000 parts per million and less than 50000 parts per million. Preferably, the protected fluorinated glucose derivative is 2-fluoro-1,3,4,6-tetra-O-acetyl-D-glucose (tetraacetylfluroglucose or pFDG), the tetraacetylmannose derivative is 1,3,4,6-tetra-0-acetyl-2-0-trifluoromethanesulphonyl-β-D- mannopyranose (tetraacetylmannose triflate), the solvent is acetonitrile, the fluoride is a fluoride ion with a potassium counter-ion, and a phase-transfer catalyst, such as 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo-[8,8,8]-hexacosa, is added to the fluoride.
EFFECT: improved method.
14 cl, 2 tbl, 3 dwg, 3 ex
SUBSTANCE: invention relates to compounds of formula , where R3 and R5 independently denote H, benzoyl, pivaloyl or methoxymethyl. The invention also
relates to a method of producing one of the said compounds
(formula 45), involving the following steps: (a) reaction of compound
with alkyl-2-bromopropionate in the presence of activated zinc in a suitable solvent to obtain a compound of formula
; (b) adding an oxidising agent to obtain a ketone of formula
; (c) fluorination of the product from step (b) to obtain a fluorinated ketone of formula
; (d) reduction of the fluorinated ketone from step (c) to obtain a compound of formula
; (e) benzylation of the product from step (d) to obtain a compound of formula
, where Bz denotes benzoyl; (f) cyclisation of the product from step (e) to obtain lactone of formula 45 as the end product.
EFFECT: lactones can be used in synthesis of nucleosides with high anti-HIV activity.
8 cl, 17 ex
SUBSTANCE: method enables to obtain 4-amino-1-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-hydroxymethyl-3-methyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one of formula (IV), which is a strong inhibitor of NS5B polymerase of hepatitis C virus (HCV).
EFFECT: high yield.
2 cl, 4 ex
FIELD: organic chemistry, chemical technology, medicine.
SUBSTANCE: invention relates to a method for preparing 1-isonicotinyl-2-D-glucosyl hydrazone. In the glucosylation reaction of isonicotinic acid hydrazide the method involves using anionite AN 31 GS as a catalyst of the enhanced effectiveness, and using 95-96.5% ethanol or 85-90% isopropanol as the reaction medium. At the final stage the method involves sorption of contaminating impurities with activated carbon followed by drying the end product in nitrogen atmosphere.
EFFECT: improved preparing method.
2 cl, 1 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to geranyl compounds represented by the following formulas (I-1) , (I-2) or (I-3) wherein R1 means compounds of the following formulas: or R2 means a group remaining after removing all carboxyl groups presenting in carboxylic acid chosen from group consisting of malic acid, citric acid, succinic acid, fumaric acid and others; m = 1, 2 or 3; n = 0, 1 or 2, and m + n represent a number of carboxylic groups presenting in indicated carboxylic acid; R3 means p-hydroxyphenyl or mercapto-group. Also, invention relates to derivatives of mevalonic acid represented by the following formula (I-4): wherein R means -CH2OH or CH3. Also, invention to an antitumor agent comprising as an active component geranyl compound of formulas (I-1), (I-2) or (I-3) or derivative of mevalonic acid of the formula (I-4), and optionally a pharmaceutically acceptable carrier or solvent. Also, invention relates to a method for treatment of liver cancer based on using geranyl compound of formulas (I-1), (I-2) or (I-3), or derivative of mevalonic acid of the formula (I-4) and using proposed compounds in manufacturing an antitumor agent. Invention provides using geranyl compounds or derivatives of mevalonic acid as antitumor agents.
EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.
7 cl, 3 tbl, 17 ex
SUBSTANCE: method involves preliminary acetylation of chitin with acetic anhydride, washing and drying the acetylated chitin in order to reduce degree of deacetylation thereof and, as a result, increase output of the desired product - D(+)-glucosamine hydrochloride when obtaining said product through hydrolysis of acetylated chitin with concentrated hydrochloric acid while heating, followed by evaporation, crystallisation, separation, washing and drying the desired product.
EFFECT: high output of the desired product while maintaining its high quality; method is more environmentally friendly since pre-treatment of chitin reduces the amount of processing wastes.
1 cl, 2 ex
SUBSTANCE: invention relates to use of 2-mercaptobenzoyl hydrazones of monose of formula (where the name of monose and value of radicals are listed in the table) as antimocrobial and antifungal agents.
EFFECT: use of 2-mercaptobenzoyl hydrazones of monose of formula (I) as antimicrobial and antifungal agents.
2 tbl, 2 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention refers to a new method for the chemical synthesis of asymmetrically or symmetrically substituted β-(1→6)-bound glucosamine disaccharide of formula (1), as well as to a method for purifying it. The invention declared the intermediate compounds referred to the given method.
EFFECT: invention refers to a pharmaceutical composition comprising the mentioned compounds, and to the use of the compounds in treating the disorders affected by immune system activity modulation, including the inhibition or activation of the immune system, such as a disorder selected from immune disorders and/or cancer.
26 cl, 8 ex, 26 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention refers to new compounds of general formula I [X]n-Y-ZR1R2, wherein the radicals are specified in the description, effective as heparan sulphate-binding protein inhibitors. The invention also refers to a pharmaceutical or veterinary composition having heparan sulphate-binding protein inhibitory activity for preventing or treating a disorder in a mammal, and to the use of these compounds and compositions for antiangiogenic, antimetastatic, anti-inflammatory, antimicrobial, anticoagulant and/or antithrombotic therapy in a mammal.
EFFECT: preparing the new compounds of general formula I [X]n-Y-ZR1R2, wherein the radicals are specified in the description, effective as the heparan sulphate binding protein inhibitors.
10 cl, 31 ex, 11 tbl, 40 dwg