- Synthesis method of high-purity histamine dihydrochloride
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The invention discloses a synthesis method of high-purity histamine dihydrochloride, and belongs to the technical field of organic synthesis. The method comprises the steps: in a solvent A, carrying out a decarboxylation reactionon L-histidine at the temperature of 110-150 DEG C under the effect of a composite decarboxylation catalyst, and carrying out filtering after the reaction is completed, wherein the composite decarboxylation catalyst is composed of a main catalyst and an auxiliary catalyst, the main catalyst is selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, pyridine, 4-methylpyridine, aniline, 4-methylaniline, ,N,N-dimethylaniline and N, N-dimethylformamide, and the auxiliary catalyst is one selected from benzophenone, acetophenone, benzophenone and p-methyl acetophenone; carrying out reduced pressure distillation on a filtrate, adding water into residues, and adjusting the pH value to 5-6 by using hydrochloric acid to obtain an aqueous solution; extracting the aqueous solution at least once by using an extracting agent to remove impurities; and evaporating to remove water in the aqueous solution, pulping with a solvent B, filtering and drying to obtain the product.
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Paragraph 0032-0046
(2021/01/28)
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- Preparation method of histamine dihydrochloride
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The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of histamine dihydrochloride. The preparation method of the histamine dihydrochloride comprises a decarboxylation reaction and a salification reaction. In the decarboxylation reaction, the raw material L-histidine is put into a mixed solvent of propylene glycol and acetophenone, the temperature is raised for reaction until the reaction liquid is clear, and the water content of each component in the decarboxylation reaction is controlled to be 0.5 wt% or below. The technical scheme provided by the invention does not need a complex catalytic system, the solvent and other raw materials are cheap and easy to obtain, the reaction endpoint control is intuitive and accurate, the obtained product has few impurities and is easy to purify, and tests prove that the method can be used for large-scale industrial production.
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Paragraph 0028-0048
(2021/07/01)
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- CONTINUOUS PROCESS FOR THE PREPARATION OF 2-(1H-IMIDAZOL-4-YL) ETHANAMINE AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
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of the invention The invention relates to a commercially viable, cost effective and energy efficient process for the preparation of 2-(1H-Imidazol-4-yl) ethanamine or pharmaceutically acceptable salts thereof in high purity and yield via application of continuous flow technology.
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Page/Page column 6
(2019/01/21)
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- Synthetic method of histamine dichloride
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The invention discloses a synthetic method of histamine dichloride, and belongs to the field of drug synthesis. The synthetic method comprises the following steps: preparing a cyano methylimidazole intermediate through oxidization of TCCA (Trichloroisocyanuric Acid) under an alkaline condition by taking L-histidine as an original raw material, and then preparing medicinal histamine dichloride through catalytic hydrogenation and one-step salifying process. In the histamine dichloride compounded through the synthetic method, the content of related substances is less than 0.5 percent, the content of a single impurity is less than 0.1 percent, and the histamine dichloride accords with medicinal level. A reagent adopted by the technology is cheap and of low-toxicity, the reaction is safe and reliable, an alcohol solvent can be recycled, after-treatment operation is simple and convenient, and the technology is environment-friendly and is beneficial for large-scale industrial production.
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Paragraph 0008; 0014; 0015
(2017/03/24)
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- A histamine dihydrochloride synthetic method
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The invention discloses a histamine dihydrochloride synthesis method. Through addition of a catalyst (copper bromide), the decarboxylation temperature is reduced, the types and the contents of unknown impurities are reduced, the raw material conversion rate is increased, the end product purity is improved, and energy consumption reduction and easy industrialisation are realized. Through the step of injecting hydrogen chloride gas to prepare hydrochlorate, the step of preparing a hydrogen chloride solution is omitted and the operation is simplified.
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- DOUBLE-ACYLATED GLP-1 DERIVATIVES
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The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue at a position corresponding to position 37 of GLP-1 (7-37) (SEQ ID NO: 1), a second K residue at a position corresponding to position 26 of GLP-1 (7-37), and a maximum of ten amino acid modifications as compared to GLP-1 (7-37), wherein the first K residue is designated K37, and the second K residue is designated K26, which derivative comprises two albumin binding moieties attached to K26 and K37, respectively, wherein the albumin binding moiety comprises a protracting moiety selected from: ????????Chem. 1:?????HOOC-(CH2)x-CO-* ????????Chem. 2:?????HOOC-C6H4-O-(CH2)y-CO-* ????????Chem. 3:?????R1-C6H4-(CH2)z-CO-* ????????Chem. 4:?????HOOC-C4SH2-(CH2)w-CO-* in which x is an integer in the range of 6-18, y is an integer in the range of 3-17, z is an integer in the range of 1-5, R1 is a group having a molar mass not higher than 150 Da, and w is an integer in the range of 6-18; with the proviso that when the protracting moiety is Chem. 1, the albumin binding moiety further comprises a linker of formula Chem. 5: *-NH-(CH2)2-(O-(CH2)2)k-O-(CH2)n-CO-*, wherein k is an integer in the range of 1-5, and n is an integer in the range of 1-5; or a pharmaceutically acceptable salt, amide, or ester thereof. The invention also relates to the pharmaceutical use thereof, for example in the treatment and/or prevention of all forms of diabetes and related diseases, as well as to corresponding novel peptides and side chain intermediates. The derivatives are suitable for oral administration.
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Paragraph 0271
(2016/07/27)
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- Rapid Conventional and Microwave-Assisted Decarboxylation of L-Histidine and Other Amino Acids via Organocatalysis with R-Carvone under Superheated Conditions
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This article reports a new methodology taking advantage of superheated chemistry via either microwave or conventional heating for the facile decarboxylation of alpha amino acids using the recoverable organocatalyst, R-carvone. The decarboxylation of amino acids is an important synthetic route to biologically active amines, and traditional methods of amino acid decarboxylation are time consuming (taking up to several days in the case of L-histidine), are narrow in scope, and make use of toxic catalysts. Decarboxylations of amino acids including L-histidine occur in just minutes while replacing toxic catalysts with green catalyst, spearmint oil. Yields are comparable to or exceed previous methods and purification of product ammonium chloride salts is aided by an isomerization reaction of residual catalyst to phenolic carvacrol. The method has been shown to be effective for the decarboxylations of a range of natural, synthetic, and protected amino acids.
- Jackson, Douglas M.,Ashley, Robert L.,Brownfield, Callan B.,Morrison, Daniel R.,Morrison, Richard W.
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p. 2691 - 2700
(2015/12/18)
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- METHOD FOR DECARBOXYLATION OF AMINO ACIDS VIA IMINE FORMATION
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The present application provides methods for decarboxylation of amino acids via imine formation with a catalyst under superheated conditions in either a microwave or oil bath.
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Page/Page column 0045; 0052; 0066; 0067
(2014/09/30)
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- COMPOUNDS AND PROCESS PREPARING A SUBSTITUTED OR AN UNSUBSTITUTED 4(5)-(OMEGA-AMINOALKYL)IMIDAZOLE
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A process is provided for preparing novel substituted or unsubstituted 4(5)-ω-aminoalkyl)imidazoles of the formula STR1 wherein n is 1 to 6, R 1 is hydrogen or a linear, branched or cyclic, saturated or unsaturated alkyl group having 1-6 C-atoms or a phenyl ring being unsubstituted, or mono-or di-substituted with groups such as lower alkyl, halogen, alkoxy, methylenedioxy or a combination thereof, and R. sub.2 is hydrogen or methyl. The process comprises brominating an ω-phthalimidoalkan-2-one with bromine in anhydrous methanol to a 1-or 3-bromo-ω-phthalimido-alkan-2-one, subjecting said derivative to ring closure with an amidine in N.N-dimethylformamide with potassium carbonate under mild conditions followed by hydrolytic separation of the phthalic residue. Pharmaceutical compounds, compositions and a method of treatment are also provided.
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