- A method for preparing [...] (by machine translation)
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The invention belongs to the field of drug synthesis; a [...] preparation method, characterized in that comprises the following steps: a [...] preparation method, characterized in that includes: 1) compound 5 under the alkaline condition and act on the hydroxylamine hydrochloride, heating the reaction to produce compound 6; 2) compound 6 in three ethylene diamine with carbonyl diimidazole role, reaction to produce compound 4; 3) compound 4 in the hydrolysis reaction under alkaline conditions, obtain arab league qi shatan thick; 4) coarse [...] refined [...]. The invention states arab league qi shatan preparation method has the short reaction time, high purity of the product, the advantage of high yield, it is suitable for large-scale industrial production. (by machine translation)
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Paragraph 0011; 0062; 0064
(2018/11/03)
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- Candesartan cilexetil preparation method
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The invention provides a novel candesartan cilexetil synthesizing path which comprises the steps of carrying out alkylation reaction on 2-ethoxy benzimidazole-7-alkyl formate and 4-bromomethyl-2'-cyano biphenyl, then hydrolyzing an ester group, then reacting with 1-halogenated ethyl cyclohexyl carbonate ester to obtain an intermediate of 1-[(2'-cyano biphenyl-4-yl) methyl)-2-ethoxy-1H-benzimidazole-7-alkyl carboxylate and then obtaining candesartan cilexetil through tetrazole reaction. The novel candesartan cilexetil synthesizing path disclosed by the invention can finish alkylation, hydrolysis and ester production reaction through a one-pot method and has a few synthesizing steps and simple technology; used raw materials are easy to obtain, production cost is low, three wastes are less, and greenness and environmental friendliness are realized.
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Paragraph 0032; 0035; 0037
(2017/09/26)
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- PROCESS FOR PREPARATION OF CANDESARTAN CILEXETIL
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There was provided a process for preparing candesartan cilexetil, the said process comprises hydrogenating a solution of trityl candesartan cilexetil in an alcohol with hydrogen in the presence of a palladium catalyst. Mixture of toluene and methanol was added to 1-(Cyclohexyloxy carbonyloxy)ethyl-2-ethoxy-1-[[2'-(N-triphenylmethyltetrazole-5-yl)biphenyl-4-yl] methyl]benzimidazole-7-carboxylate and hydrogenated at room temperature with hydrogen at atmospheric pressure in the presence of palladium on carbon until the hydrogen uptake was ceased. Filtered over celite bed, washed the bed with a mixture of toluene and methanol, filtrate was collected and concentrated. Co- distilled with acetonitrile, acetonitrile was added, stirred at room temperature, cooled to 0°C. stirred, filtered, washed with chilled acetonitrile and dried to get candesartan cilexetil.
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Page/Page column 3
(2010/01/30)
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- PROCESS FOR PREPARING CANDESARTAN CILEXETIL
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A process for preparing candesartan cilexetil.
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Page/Page column 16; 21-22
(2010/10/19)
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- CRYSTAL AND PROCESS FOR PRODUCING THE SAME
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A process for producing crystals of 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimdazole-7-carboxylic acid (compound (I)), characterized by dissolving or suspending the compound (I) or a salt thereof in a solvent comprising an aprotic polar solvent and crystallizing it. By the process, the contaminants which are contained in the compound (I) or its salt and are difficult to remove, such as tin compounds, analogues of the compound (I), and a residual organic solvent, can be easily removed. Crystals of the compound (I) can be efficiently and easily mass-produced in high yield on an industrial scale.
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- Nonpeptide Angiotensin II Receptor Antagonists. Synthesis and Biological Activity of Benzimidazolecarboxylic Acids
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A series of 2-substituted-1--1H-benzimidazole-7-carboxylic acids was prepared from the key intermediate 3-amino-2-amino>benzoate (6a-c) in order to clarify the structure-activity relationships of various analogues of 2-butyl-1-methyl>-1H-benzimidazole-7-carboxylic acid (CV-11194), a potent and long acting angiotensin II (AII) receptor antagonist.The AII antagonistic activity of the benzimidazoles was investigated by in vitro assays, which included an AII receptor binding assay and AII-induced vasocontraction assay, as well as by in vivo assays such as an AII-induced pressor response in rats.Most of the benzimidazoles showed high affinity for the AII receptor (IC50 value, 10-6-1--7 M) and inhibited the AII-induced pressor response at 1 or 3 mg/kg po, and the effects were more potent than those of CV-11194 and DuP 753.The structure-activity relationship studies on the binding affinity and the inhibition of AII-induced pressor response suggested that straight chains of a certain length (e.g., ethoxy groups, ethyl groups) were the best as substituents at the 2-position and that their steric factors, lipohilicity, and electronic effects affected the potency of the AII antagonistic action.Both a carboxyl group at the 7-position and a tetrazole ring at the 2'-position were particularly important for potent and orally active AII antagonistic activity and a long-acting hypotensive effect.The representative compound, 2-ethoxy-1-methyl>-1H-benzimidazole-7-carboxylic acid (26b, CV-11974), inhibited the specific binding of AII to bovine adrenal cortical membrane with an IC50 value of 1.1*10-7 M.The AII-induced contraction of rabbit aortic strips was antagonized by CV-11974 (IC50 value, 3.0*1--10 M).Oral administration of CV-11974 to conscious normatensive rats at 1 mg/kg resulted in long-lasting inhibition of the AII-induced pressor response.CV-11974 at 0.1-1 mg/kg iv reduced blood pressure dose-dependently in spontaneously hypertensive rats.
- Kubo, Keiji,Kohara, Yasuhisa,Imamiya, Eiko,Sugiura, Yoshihiro,Inada, Yoshiyuki,et al.
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p. 2182 - 2195
(2007/10/02)
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