- Preparation method of high-purity triphenyl olmesartan ethyl ester
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The invention provides a preparation method of a high-purity olmesartan medoxomil intermediate triphenyl olmesartan ethyl ester. The provided preparation method specifically comprises the steps that in a first solvent, in the presence of a combined catalyst and potassium carbonate, a compound shown in a formula 2 and a compound shown in a formula 3 react with each other to obtain a compound shownin a formula 1, wherein the combined catalyst is composed of polyethylene glycol and 2-methylpyrrolidone. The preparation method can significantly reduce the content of the impurities shown in a formula 4 and formula 5 in the product intermediate shown in the formula 1, and improve the purity of the intermediate shown in the formula 1.
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- Method for synthesizing olmesartan medoxomil intermediate impurities
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The invention relates to the field of medicines and in particular relates to a method for synthesizing olmesartan medoxomil intermediate impurities. The olmesartan medoxomil intermediate impurities respectively refer to an impurity C, an impurity D and an impurity F. The respective synthetic reaction equations of the impurities are shown in the followings. The method specifically comprises the following steps: (1) taking an intermediate I as a raw material, and performing reactive deprotection with acetic acid so as to obtain the impurity C; (2) hydrolyzing an initial material B {4-[2-(trityl tetrazol-5-yl)phenyl] benzyl bromide} in a reaction system so as to obtain the impurity D; and (3) hydrolyzing an intermediate II into carboxylic acid in the reaction system, thereby obtaining the impurity F. According to the synthetic method for preparing the impurities, disclosed by the invention, a high-purity reference substance is conveniently obtained, and due to the optimized process, production of the impurities is specifically controlled, so that the quality of the raw drugs is improved. The reaction equation of the impurity C is as shown in the specification. The reaction equation of the impurity D is as shown in the specification. The reaction equation of the impurity F is as shown in the specification.
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Paragraph 0033; 0034; 0035; 0042; 0043; 0044
(2017/07/21)
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- DEPROTECTION METHOD FOR TETRAZOLE COMPOUND
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The present invention relates to a method of deprotecting a tetrazole compound, useful as an intermediate for angiotensin II receptor blockers, and provides a novel production method of angiotensin II receptor blockers. Provided is a production method of a compound represented by the formula [3] or [4] or a salt thereof, including (i) reducing a compound represented by the formula [1] or [2] or a salt thereof in the presence of a metal catalyst and an alkaline earth metal salt, or (ii) reacting the compound with a particular amount of Br?nsted acid: wherein each symbol is as defined in the present specification.
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- METHOD FOR PRODUCING BIARYL COMPOUND
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Provided is a novel production method capable of producing a biaryl compound, which is useful as an intermediate for angiotensin II receptor blockers, economically under conditions suitable for industrial production. A production method of a biaryl compound of the formula [3] or a salt thereof, including reacting a 2-phenylazole derivative of the formula [1] or a salt thereof, with a benzene derivative of the formula [2] or a salt thereof in the presence of a metal catalyst, a base, and one or more kinds of compounds selected from the group consisting of (a) a monocarboxylic acid metal salt, (b) a dicarboxylic acid metal salt, (c) a sulfonic acid metal salt, and (d) a phosphate or phosphoric amide metal salt represented by RAxP(O)(OM)y wherein each symbol is as defined in the DESCRIPTION.
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- Novel and efficient debenzylation of N-benzyltetrazole derivatives with the rosenmund catalyst
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The Rosenmund catalyst (Pd/BaSO4) was found to efficiently catalyze debenzylation of N-benzyltetrazole derivatives with ammonium formate by catalytic transfer hydrogenation under mild conditions. The protocol has been applied to functionalized substrates to provide various angiotensin II receptor blockers in excellent yields.
- Seki, Masahiko
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p. 3249 - 3255
(2015/01/08)
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- METHOD FOR PRODUCING 1-BIPHENYLMETHYLIMIDAZOLE COMPOUND
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The present invention provides a method for producing a 1-biphenylmethylimidazole compound having superior angiotensin II receptor antagonistic activity, or an intermediate thereof. The present invention provides a method for producing a compound having the formula (5) (R1 , Ra : H, an alkyl group) by oxidizing a compound having the formula (1) (R a : H, an alkyl group) using an oxidizing agent in the presence of a radical initiation reagent, and then reacting with an ammonia-generating reagent and a compound having the formula R 1 CHO (R 1 : H, an alkyl group) or a compound having the formula R1C(ORb)3 (R1: H,an alkyl group; Rb : an alkyl group).
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Page/Page column 31
(2011/04/18)
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- ANGIOTENSIN II ANTAGONIST 1-BIPHENYLMETHYLIMIDAZOLE COMPOUNDS AND THEIR THERAPEUTIC USE
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Compounds of the following formula (I) or the formula (I) p : STR1 wherein R 1 is alkyl or alkenyl; R 2 and R 3 are hydrogen, alkyl, alkenyl, cycloalkyl, aralkyl, aryl, or aryl fused to cycloalkyl; R 4 is hydrogen, alkyl, alkanoyl, alkenoyl, arylcarbonyl, alkoxycarbonyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrothienyl, tetrahydrofuryl, a group of formula--SiR a R b R c, in which R a, R b and R c are alkyl or aryl, alkoxymethyl, (alkoxyalkoxy)methyl, haloalkoxymethyl, aralkyl, aryl or alkanoyloxymethoxycarbonyl; R 5 is carboxy or--CONR 8 R 9, wherein R 8 and R 9 hydrogens or alkyl, or R 8 and R 9 together form alkylene; R 6 is hydrogen, alkyl, alkoxy or halogen; R. sup.7 is carboxy or tetrazol-5-yl; R p. sup.1 is hydrogen, alkyl, cycloalkyl or alkanoyl; R p 2 is a single bond, alkylene or alkylidene; R p 3 and R p 4 are each hydrogen or alkyl; R. sub.p 6 is carboxy or tetrazol-5-yl; and X p is oxygen or sulfur; and pharmaceutically acceptable salts and esters thereof. The compounds are AII receptor antagonists and thus have hypotensive activity and can be used for the treatment and prophylaxis of hypertension. The compounds may be prepared by reacting a biphenylmethyl compound with an imidazole compound.
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- Nonpeptide angiotensin II receptor antagonists: Synthesis, biological activities, and structure - Activity relationships of imidazole-5-carboxylic acids bearing alkyl, alkenyl, and hydroxyalkyl substituents at the 4-position and their related compounds
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A series of imidazole-5-carboxylic acids bearing alkyl, alkenyl, and hydroxyalkyl substituents at the 4-position and their related compounds were prepared and evaluated for their antagonistic activities to the angiotensin II (AII) receptor. Among them, the 4-(1-hydroxyalkyl)-imidazole derivatives had strong binding affinity to the AII receptor and potently inhibited the AII-induced pressor response by intravenous administration. Various esters of these acids showed potent and long-lasting antagonistic activity by oral administration. The most promising compounds were (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (CS-866) and (pivaloyloxy)-methyl esters of 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[(2′-1H-tetrazol-5-ylbiphenyl-4-yl) -methyl]imidazole-5-carboxylic acid (26c). A study involving stereochemical comparison of 26c with the acetylated C-terminal pentapeptide of AII was also undertaken.
- Yanagisawa, Hiroaki,Amemiya, Yoshiya,Kanazaki, Takuro,Shimoji, Yasuo,Fujimoto, Koichi,Kitahara, Yoshiko,Sada, Toshio,Mizuno, Makoto,Ikeda, Masahiro,Miyamoto, Shuichi,Furukawa, Youji,Koike, Hiroyuki
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p. 323 - 338
(2007/10/03)
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