- Preparation method of funolasan fumarate
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The present invention provides a method for preparing funorasine fumarate, comprising the following steps: (1) the compound of formula I is azidine to give a compound of formula II.; (2) the compound of formula II. is cyclized with the compound of formula III. to give a compound of formula IV.; (3) the compound of formula IV. is condensed with a compound of formula VI. to give a compound of formula VII. compound; (4) a compound of formula VII. is deprotected with acid to obtain a vonorasin free base; (5) a vonorasin free base is salted with fumarate to give vonorasin fumarate. According to the method of the present invention to synthesize vonoracin fumarate, compared with the prior art, the total yield of vonora fumarate increased to more than 60%, and the yield has been greatly improved. Furthermore, compound formula IV. can be used as a new intermediate for the preparation of funolasine fumarate.
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- Vonoprazan fumarate intermediate and preparation method thereof
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The invention provides a vonoprazan fumarate intermediate compound as well as a preparation method and application thereof. Compared with the prior art, the technical scheme provided by the invention avoids the hydrogenation reaction operation with higher
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Paragraph 0039; 0084; 0086-0087; 0089-0090; 0092
(2021/10/27)
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- Vonoprazan salt as well as preparation method and application thereof
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The invention discloses vonoprazan salt as well as a preparation method and application thereof, and the vonoprazan salt is salt formed by vonoprazan and a complex of organic acid and bismuth. The invention also comprises a preparation method of the vonoprazan salt and application of the vonoprazan salt in preparation of drugs for treating gastric acid diseases. Compared with the existing vonoprazan salt, the salt formed by the vonoprazan and the complex of organic acid and bismuth has many satisfactory advantages, such as good solubility and stability, improvement of bioavailability, synergistic increase of drug effect and the like.
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Paragraph 0050; 0055-0060
(2021/05/26)
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- Preparation method of high purity funolasine fumarate
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The present invention discloses a method for preparing a pure vonorasine fumarate, comprising the following steps: 5- (2-fluorophenyl)-1 [(pyridin-3-yl) sulfonyl] -1H- pyrrole-3-formaldehyde as the starting material, the starting material is dissolved in
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Paragraph 0065-0070
(2022/01/08)
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- Vonoprazan purification method
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The invention discloses a purification method of vonoprazan. The method comprises the following steps: preparing a refined solvent from a monohydric alcohol, formamide and water according to a certainratio; and purifying a vonoprazan crude product under t
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Paragraph 0031; 0034
(2020/05/01)
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- Novel method for synthesizing Vonoprazan through one-step process
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The invention discloses a novel method for synthesizing Vonoprazan through a one-step process, belonging to the field of medicines. The method comprises the following steps: dissolving a compound namely 5-(2-fluorophenyl)-1H-pyrrole-3-formaldehyde into an
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Paragraph 0034-0037; 0046-0053
(2019/10/05)
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- Preparation method of vonoprazan
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The invention relates to a preparation method of vonopraza. The preparation method of the vonoprazan, provided by the invention, comprises the following steps of taking 2-bromo-2'-fluoroacetophenone shown as a formula 3 as a starting raw material; reactin
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- Preparation method of low-impurity Vonoprazan fumarate
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The invention provides a preparation method of low-impurity Vonoprazan fumarate. A method for removing impurities A-E during preparation of Vonoprazan comprises the steps: preparing Vonoprazan hydrobromide from Vonorazan, and removing the impurities A-E which are difficult to remove by using a recrystallization purifying method, wherein the method for removing the impurities A-E during preparationof Vonoprazan has good selectivity to the impurities A-E. The preparation method of low-impurity Vonoprazan fumarate comprises the steps: performing a reaction on 5-(2-fluorophenyl)-1-(pyridyl-3-ylsulfonyl)-1H-pyrrole-3-formaldehyde and methylamine or a salt of methylamine, then performing reduction so as to obtain Vonoprazan, then preparing Vonoprazan hydrobromide, then performing salt dissociation so as to obtain Vonoprazan free alkali, preparing Vonoprazan fumarate with a purity of 99.7% or above, and then performing recrystallization refining so as to obtain Vonoprazan fumarate with a purity of 99.9% or above. The invention provides an impurity D, a preparation method of the impurity D and application of the impurity D as an impurity reference substance in Vonoprazan fumarate.
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- Post-treatment purification method of vonoprazan intermediate
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The invention provides a post-treatment purification method of a chemical drug vonoprazan intermediate 1-[5-(2-fluorophenyl)-1-(pyridine-3-ylsulfonyl)-1H-pyrrole-3-yl]-N-methyl methylamine compound for treatment of gastric ulcer, duodenal ulcer and reflux
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Paragraph 0018-0033
(2019/12/25)
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- Substituted pyrrole-4-alkylamine compounds and application thereof
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The invention relates to substituted pyrrole-4-alkylamine compounds and application thereof. The invention particularly provides application of compounds shown in a formula I, or optical isomers thereof, or racemates thereof, or solvates thereof, or pharm
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- The preparation method of the fumaric acid fertile norah approves
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The invention relates to the field of drug preparation researches, and especially relates to a preparation method of 1-[5-(2-fluorophenyl)-1-(pyridyl-3-ylsulfonyl)-1H-pyrryl-3-yl]-N-methyl methylamine fumarate (represented by formula I) and an intermediate thereof. The method is characterized in that the above compound represented by formula (I) is prepared through nitrogen monomethylation and salt formation with a compound represented by formula (V) as an important intermediate. The structural formula of the compound represented by formula (V) is shown in the specification, and the structural formula of the compound represented by formula (I) is also shown in the specification.
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- Preparation method of vonoprazan fumarate
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The invention relates to a preparation method of vonoprazan fumarate, belonging to the technical field of preparation of a raw material medicine. The preparation method of the vonoprazan fumarate comprises the following steps: 5-(2-fluorophenyl)-1H-pyrrole-3-carbonitrile is used as a starting material to react with pyridine-3-sulfonyl chloride to form 5-(2-fluorophenyl)-1-(pyridine-3-sulfonyl)-1H-pyrrole-3-nitrile; the 5-(2-fluorophenyl)-1-(pyridine-3-sulfonyl)-1H-pyrrole-3-nitrile is reduced to prepare 5-(2-fluorophenyl)-1-(pyridine-3-sulfonyl)-1H-pyrrole-3-formaldehyde; then vonoprazan is prepared; and then a salt formation step is used to prepare the vonoprazan fumarate. The preparation method is suitable for industrial production.
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- Novel and practical synthesis of vonoprazan fumarate
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A novel and practical strategy for the synthesis of vonoprazan fumarate 1, a novel potassium-competitive acid blocker, has been developed. Vonoprazan fumarate was obtained through a four-step process starting from 5-(2-fluorophenyl)-1H-pyrrole-3-carboxylate and including ester hydrolyzing, methylamine substitution, sulfonyl chloride substitution, and amide reduction. Key to the strategy is the amide reduction taking a novel and practical protocol. The main advantages of this route include two parts: controllable impurity and acceptable overall yield.
- Yu, Qian-Ying,Zeng, Huang,Yao, Kai,Li, Jian-Qi,Liu, Yu
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supporting information
p. 1169 - 1174
(2017/06/09)
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- Vonoprazan fumarate preparation method
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The invention concretely relates to a vonoprazan fumarate preparation method, and belongs to the field of medicines and chemical engineering. The method comprises the following steps: 1, carrying out condensation on 2-fluoroacetophenone used as an initial raw material and allylamine to obtain a compound IV; 2, carrying out a ring closing reaction on the compound IV under the catalysis of a copper catalyst in the presence of a ligand in order to obtain a compound V; 3, carrying out a sulfoamidation reaction on the compound V and pyridine-3-sulfonyl chloride to generate a compound VII; 4, carrying out a bromination reaction on the compound VII by using N-bromosuccimide in order to generate a compound VIII; 5, carrying out an amination reaction on the compound VIII and methylamine hydrochloride under the action of a catalyst and an alkali in order to obtain vonoprazan alkali; and 6, carrying out salt formation on the vonoprazan alkali and fumaric acid in order to obtain vonoprazan fumarate. The preparation method has the advantages of simplicity in operation, mild reaction conditions, high yield and high purity of the product, and easiness in industrial production.
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- A preparation method of the fumaric acid fertile norah approves
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The invention discloses a preparation method of vonoprazan fumarate. The preparation method includes: S1, dissolving 5-(2-fluorophenyl)-1H-pyrrole-3-carboxaldehyde (I) in organic solvent, mixing with methylamine alcohol solution for 6-8h to generate imine
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Paragraph 0066; 0076-0078; 0092; 0103
(2018/04/01)
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- Preparation method of vonoprazan fumarate
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The invention provides a preparation method of vonoprazan fumarate. The preparation method comprises the following steps of enabling 5-(2-fluorophenyl)-1-(pyridine-3-sulfonyl)-1-H-pyrrole-3-formaldehyde and methylamine to react to generate Schiff base; us
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Paragraph 0007; 0020; 0021; 0022; 0023
(2017/08/31)
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- Preparation method of vonoprazan key intermediate
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The invention relates to a preparation method of a vonoprazan key intermediate, and belongs to the technical field of preparation of vonoprazan intermediates. The preparation method of the vonoprazan key intermediate comprises the steps: with 5-(2-fluorop
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Paragraph 0023-0033
(2017/03/14)
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- Synthesis method of 5-(2-fluorophenyl)-N-methyl-1-(3-pyridyl sulfonyl)-1H-pyrrole-3-methanamine fumarate TAK438
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The present invention relates to a synthesis method of 5-(2-fluorophenyl)-N-methyl-1-(3-pyridyl sulfonyl)-1H-pyrrole-3-methanamine fumarate TAK438. The synthesis route of TAK 438 in the prior art reduces cyan into an aldehyde structure, which then perform
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- Proton pump inhibitors
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A proton pump inhibitor containing a compound represented by the formula (I) wherein X and Y are the same or different and each is a bond or a spacer having 1 to 20 carbon atoms in the main chain, R 1 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, R 2 , R 3 and R 4 are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted thienyl group, an optionally substituted benzo[b]thienyl group, an optionally substituted furyl group, an optionally substituted pyridyl group, an optionally substituted pyrazolyl group, an optionally substituted pyrimidinyl group, an acyl group, a halogen atom, a cyano group or a nitro group, R 5 and R 6 are the same or different and each is a hydrogen atom or an optionally substituted hydrocarbon group, which has a superior proton pump action and shows an antiulcer activity and the like after conversion to a proton pump inhibitor in the body, or a salt thereof. or a prodrug thereof is provided.
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- Discovery of a novel pyrrole derivative 1-[5-(2-fluorophenyl)-1-(pyridin-3- ylsulfonyl)-1 H -pyrrol-3-yl]- n -methylmethanamine fumarate (tak-438) as a Potassium-Competitive Acid Blocker (P-CAB)
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In our pursuit of developing a novel and potent potassium-competitive acid blocker (P-CAB), we synthesized pyrrole derivatives focusing on compounds with low log"‰D and high ligand-lipophilicity efficiency (LLE) values. Among the compounds synthesized, the compound 13e exhibited potent H +,K+-ATPase inhibitory activity and potent gastric acid secretion inhibitory action in vivo. Its maximum efficacy was more potent and its duration of action was much longer than those of proton pump inhibitors (PPIs). Therefore, compound 13e (1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)- 1H-pyrrol-3-yl]-N-methylmethanamine fumarate, TAK-438) was selected as a drug candidate for the treatment of gastroesophageal reflux disease (GERD), peptic ulcer, and other acid-related diseases.
- Arikawa, Yasuyoshi,Nishida, Haruyuki,Kurasawa, Osamu,Hasuoka, Atsushi,Hirase, Keizo,Inatomi, Nobuhiro,Hori, Yasunobu,Matsukawa, Jun,Imanishi, Akio,Kondo, Mitsuyo,Tarui, Naoki,Hamada, Teruki,Takagi, Terufumi,Takeuchi, Toshiyuki,Kajino, Masahiro
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p. 4446 - 4456
(2012/07/28)
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- PROTON PUMP INHIBITORS
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Proton pump inhibitors which have excellent proton pumping activity and which can be converted in vivo into proton pump inhibitors to exhibit antiulcer effect and so on, containing compounds represented by the general formula (I) or salts thereof or prodrugs of the same: (I) wherein X and Y are each independently a free valency or a spacer whose main chain has 1 to 20 carbon atoms; R1 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; R2, R3 and R4 are each independently hydrogen, an optionally substituted hydrocarbon group, optionally substituted thienyl, optionally substituted benzo[b]thienyl, optionally substituted furyl, optionally substituted pyridyl, optionally substituted pyrazolyl, optionally substituted pyrimidinyl, acyl, halogeno, cyano, or nitro; and R5 and R6 are each independently hydrogen or an optionally substituted hydrocarbon group.
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Page/Page column 338-339; 387
(2010/10/20)
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