The method of obtaining 4,1'6'-trichloro-4,1',6'- trimethoxybenzoate
4,1', 6'-Trichloro-4,1', 6'-trimethoxybenzoate obtained by selective acetylation of sucrose in pyridine, chlorination obtained 6-monoacetylmorphine product in the provisions of 4,1', 6', paramilitary obtained in chlorinated pyridine and subsequent dezazetilirovanie and selection of the target product. From the reaction zone selective acetylation is removed by distillation with freezing the excess pyridine. Full acetate 4,1', 6'-trichloro-4,1', 6'-trimethoxybenzoate allocate by vicadine water. Dezazetilirovanie carried out with a solution of sodium methoxide in ethanol at room temperature for at least 4 h at pH 9, the resulting solution is neutralized, discolor and evaporated in vacuo to a dry residue. Chlorination lead suspension obtained by adding to the DMF petaluridae phosphorus. Processes for the preparation of suspensions and chlorination is carried out in a single reaction volume. The technical result is an increase in the yield of the target product. 2 C. p. F.-ly. Tablicy
Claims1. The method of obtaining 4,1’,6’-trichloro-4,1’,6’-deoxyglycosides on the basis of sucrose, including the electoral atsetilirovaniya obtained in chlorinated pyridine and subsequent dezazetilirovanie and selection of the target product, characterized in that the reaction zone selective acetylation is removed by distillation with freezing the excess pyridine, and received by paramilitaries full acetate 4,1’,6’-trichloro-4,1’,6’-deoxyglycosides allocate by vicadine water, dezazetilirovanie carried out with a solution of sodium methoxide in ethanol at room temperature for at least 4 h at pH 9, the resulting solution is neutralized, discolor and evaporated in vacuo to a dry residue.2. Method p. 1, characterized in that the chlorination product selective acetylation lead suspension obtained by adding to the DMF petaluridae phosphorus under vigorous stirring and at a temperature below 20With, by adding a solution of 6-monoacetate sucrose in DMF at a temperature below 20C followed by warming the reaction mixture to 108-110C for no more than 2 hours and keeping at 108-110C for at least 1.5 hours3. The method according to p. 2, characterized in that the preparation processes of the suspension and chlorination are in a single reaction volume.
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