34 results about "Glutamic acid diethyl ester" patented technology

The invention discloses a preparation method of Raltitrexed. The method comprises steps of: carrying out alkaline hydrolysis on N-[[5-[(1,4- dihydro-2-methyl-4-oxygen-6quinazoline) methyl] formoxyl-]-2-thiophene] formyl]-L-glutamic acid diethyl ester with existence of a certain proportion of alcoholic solvent; filtering out insoluble substances after the reaction; then extracting with an organic solvent; adjusting a pH of a water layer to 6-7 during neutralization to precipitate a small amount of viscous solid and stirring for 1-3 h; After complete solidification of a product, adjusting a pH to 2-3 to precipitate all of the product; dissolving a crude product with an organic solvent; filtering an depriving insoluble substances; adding water and crystallizing to obtain a finished product. The preparation method of the present invention well solves a problem, which commonly exists in a technology, of severe exceeding of standard of residue on ignition, has simple operations, produces high-quality product with high yield and is suitable for industrialized production.

The invention discloses a preparation method of pemetrexed disodium, which comprises the following steps: preparing 4-(4,4-dialkoxy-1-butenyl)benzoate 6 and 4-(3-formyl-3-halo-1-propenyl)benzoate 7, carrying out ring-closing reaction on the compound 7 and 2,4-diamido-6-hydroxypyrimidine under the action of an alkali to obtain a compound 9; carrying saponification on the compound 9, and acidifying to obtain a compound 10; carrying out condensation reaction on the compound 10 and diethyl L-glutamate to obtain a compound 11; carrying out catalytic hydrogenation reaction on the compound 11 under the action of a catalyst to obtain a compound 12; and carrying out hydrolysis reaction on the compound 12 under the action of an alkali to obtain the target product pemetrexed disodium 1. The method has the advantages of accessible raw materials, wide sources, low preparation cost and low price, is suitable for industrial production, and solves the problems of high preparation cost and difficulty for industrial production in the prior art.

The synthesis of anticancer medicine Raltitrexed with 2, 5-thienyl diformic acid and diethyl glutamate as initial material and through six reaction steps of monocondensation, rearrangement, N-methylation, e;limination of tert-butoxy carbonyl group, condensation with 6-bromomethyl-2-methyl-4-quinbolone and saponification. The present invention has total yield of 18.1%, higher than that of available synthesis line, less reaction steps, mild condition and simple operation, and is suitable for mass production.

The invention relates to composition (a compound molecular probe preparation) containing various radioactive compounds such as <18>F-FDG (<18>F-fludeoxyglucose), <18>F-FPA (2-<18>F-fluoropropionic acid) and / or <18>F-NFPGlu ((N-2-<18>F-fluoropropionyl)-L-alpha-glutamic acid), a one-time radioactive synthesis method of the composition and an application of the composition in preparation of positron emission computed tomography drugs. The composition comprising <18>F-FDG+<18>F-FPA and <18>F-FDG+<18>F-NFPGlu or <18>F-FDG+<18>F-FPA+<18>F-NFPGlu as PET drugs can be obtained from precursors through nucleophilic fluorination reaction and a hydrolysis reaction, wherein the precursors comprise a mannose triflate and ethyl 2-bromopropionate mixture and a mannose triflate and (N-2-bromopropionyl)-L-alpha-diethyl glutamate mixture or a mixture of mannose triflate, ethyl 2-bromopropionate and (N-2-bromopropionyl)-L-alpha-diethyl glutamate. The composition can be used for differential diagnosis and therapeutic effect evaluation of tumor, cardiovascular and cerebrovascular diseases and nervous and mental diseases and can overcome limitation of <18>F-FDG.

The invention relates to an intermediate of pemetrexed disodium, a preparation method thereof and a method for preparing pemetrexed disodium thereby; and the intermediate is (2-(4-(3-(2,4-diamino-6-oxy-1,6-dihydro-pyridine-5-group)-3-(1,3)dioxolane-2-group-propyl) benzylamine)sodium glutaric acid. The synthesis of the intermediate comprises the following steps: firstly, condensation reaction is conducted on 4-bromobenzoic acid or 4-iodobenzoic acid and L-glutamate diethylester, then Hack reaction is conducted, 4-bromo is replaced and 4-butyraldehyde is formed, then selective bromo replacementis conducted and the 4-butyladehyde is converted into 2-bromobutyraldehyde, and then condensation reaction of aldehyde and ethylene glycol is utilized for protecting the aldehyde, and pyrimidine ringis further synthesized, and finally the intermediate is obtained. Acid hydrolysis ring-closing reaction and sodium hydroxide salification are respectively conducted for once on the intermediate so asto obtain the pemetrexed disodium. The method for preparing pemetrexed disodium in the invention has high yield, low cost and easy operation and is applicable to industrialized production.

The invention discloses a gas chromatography detection method for ethyl chloride in L-glutamic acid diethyl ester hydrochloride. It dissolves the L-glutamic acid diethyl ester hydrochloride sample and then injects the headspace sample, and adopts the GC-ECD detection method to qualitatively and quantitatively analyze the ethyl chloride in the L-glutamic acid diethyl ester hydrochloride. The method has been validated, and the method has the advantages of strong specificity, rapidity and sensitivity. The present invention first establishes the qualitative and quantitative method of ethyl chloride in L-glutamic acid diethyl ester hydrochloride using GC-ECD detection method, which is convenient to control the quality of L-glutamic acid diethyl ester hydrochloride .

The invention discloses a separation and detection method of L-glutamic acid diethyl ester hydrochloride and its optical isomers. The separation and detection method adopts high performance liquid chromatography, the stationary phase is a silica gel chiral column, and the mobile phase is Reverse phase solvent: Perchloric acid in water - acetonitrile. The method of the invention has the characteristics of good separation, high sensitivity, strong specificity, etc., and can quickly and accurately perform quality control on L-diethyl glutamate hydrochloride.

The invention relates to the technical field of medicine preparation, in particular to a synthesis process of a Raltitrexed key intermediate. According to the synthesis process of the Raltitrexed keyintermediate, forming an active intermediate (isocyanate) through glutamate diethyl ester, the active intermediate and N-methyl-(2-thienyl) tert-butyl carbamate are directly reacted, and a target product N-[5-[N-(t-butyloxycarboryl)-N-methyl amino]-2-thenoyl]-L-glutamate diethyl ester is prepared by two steps. The synthesis process avoids difficulties of potential risks of part of racemization ofa chiral center caused by amidation reaction, low yield, complicated operation and purification and the like. The synthesis process of the Raltitrexed key intermediate is simple to operate, short in line, environmentally friendly and high in yield.

The invention provides a poly (gamma-oligomerization ethylene glycol monomethyl ether-L-glutamic acid diethyl ester) - polyamino acid diblock copolymer and a preparation method thereof, and further expands the application of polyamino acid materials to the field of biological medicine. A structural general formula of the diblock polyamino acid is shown in , wherein j is an integer from 1 to 10, m is an integer from 5 to 200, n is an integer from 5 to 200, R1 is an initiator end group, and R2 is an alpha-amino acid side chain group. The invention further provides a preparation method of poly (gamma-oligomerization ethylene glycol monomethyl ether-L-glutamic acid diethyl ester) - polyamino acid. The diblock copolymer not only is simple in preparation process and good in biocompatibility, but also has thermosensitive properties, and can be applied to the field of the biological medicine of targeted medicine delivery and the like.

The invention discloses automatic synthesis methods of two enantiomorphous glutamic acid PET (Positron Emission Tomography) imaging agents, namely, (N-2-<18>F-)fluoropropionyl-L-alpha-glutamic acid(<18>F-NFPGlu) and (N-2-<18>F-)fluoropropionyl-D-alpha-glutamic acid(<18>F-DFPGlu), and preparation methods of corresponding precursors, namely, (N-2-bromo-propionyl)-L-alpha-glutamate diethyl ester and (N-2-bromo-propionyl)-D-alpha-glutamate diethyl ester. The invention relates to organic synthesis of a <18>F-NFPGlu precursor and a <18>F-DFPGlu precursor and realization of short-time, high-yield and automatic radio-synthesis of <18>F-NFPGlu and <18>F-DFPGlu by taking corresponding precursors as starting raw materials through a simple 'two-step on-column thermal decomposition method'. The radio-synthesis method can also be applied to synthesis of a <18>F-labeled beta-glutamic acid-NH2 group imino acid compound, namely, (N-2-<18>F-fluoropropionyl)-beta-glutamic acid (<18>F-NFPBGlue) and a precursor thereof. The formula is shown in the specification.