- Preparation method of pyrrole compound
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The invention relates to the field of medicinal chemistry, in particular to a preparation method of a pyrrole compound. The method comprises the following steps: reacting raw materials with propionitrile in the presence of a phase transfer catalyst and an alkali reagent, and then carrying out a ring closing reaction, a substitution reaction, a sulfonylation reaction and a condensation reaction to obtain a target compound. The method is relatively short in route, simple, convenient and easy to implement, and can be used for industrial production.
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- Fumaric acid fertile norah approves of the preparation process
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The invention relates to a preparation technology for vonoprazan fumarate. The preparation method comprises: reacting 2'-fluoroacetophenone (II) with ammonium acetate to generate 1-(2-fluorophenyl)ethen-1-amine (III), then reacting with 2-bromopropanal for cyclization for generating 2-(2-fluorophenyl)-4-methyl-1H-pyrrole (IV), reacting the compound IV with 3-pyridinesulfonyl chloride to generate 5-(2-fluorophenyl)-3-methyl-1-(pyridin-3-ylsulfonyl)-1H-pyrrole (V), then performing N-bromosuccinimide substitution to generate 5-(2-fluorophenyl)-3-bromomethyl-1-(pyridin-3-ylsulfonyl)-1H-pyrrole (VI), and finally performing methylamination reaction and salt forming, so as to obtain vonoprazan fumarate. The method avoids usage of a toxic reagent liquid bromine and hydrogen chloride gas capable of corroding equipment in the prior art, possesses the advantages of simple technological route, mild reaction conditions, controllable operation, environment friendliness and high product yield, and is suitable for large-scale industrialized production.
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Paragraph 0044-0049
(2017/09/01)
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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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- Preparation method of vonoprazan fumarate intermediate namely 5-(2-fluorophenyl)-1H-pyrrole-3-methanal
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The invention relates to a preparation method of a vonoprazan fumarate intermediate namely 5-(2-fluorophenyl)-1H-pyrrole-3-methanal, and belongs to the technical field of chemical industry. The preparation method comprises the following steps of (1) by using 2-fluoroacetophenone as an initial raw material, enabling the 2-fluoroacetophenone and allylamine to be subjected to condensation so as to obtain a compound IV; (2) under the catalysis of a metal catalyst, and under the condition that a ligand is provided, enabling the compound IV to be subjected to a ring-closing reaction so as to obtain a compound V; and (3) sequentially performing bromination, hydolysis and oxidation reactions by using the compound V so as to obtain the 5-(2-fluorophenyl)-1H-pyrrole-3-methanal. According to the preparation method disclosed by the invention, reagents of bromine, hydrogen chloride and the like, which have strong corrosivity, are prevented from being used, and flammable hydrogenation reducing agents of palladium on carbon, raneys nickel, diisobutylaluminium hydride and the like are also prevented from being used; and besides, the technological line is simple to operate, the reaction condition is mild, the product yield is high, the purity is high, and industrialized production is easy to realize.
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- α-Palladation of imines as entry to dehydrogenative heck reaction: Aerobic oxidative cyclization of N-allylimines to pyrroles
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We report here a palladium(II)-catalyzed oxidative cyclization reaction of N-allylimines derived from methyl ketones, typically acetophenones, affording pyrrole derivatives at room temperature under oxygen atmosphere. The reaction likely proceeds through α-palladation of the imine followed by olefin migratory insertion and β-hydride elimination, thus representing a new example of aerobic dehydrogenative Heck cyclization.
- Chen, Zhiyuan,Lu, Beili,Ding, Zhenhua,Gao, Ke,Yoshikai, Naohiko
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supporting information
p. 1966 - 1969
(2013/06/04)
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