88150-75-8

Usage

Uses

Used in Pharmaceutical Industry:
ETHYL4-[2-(1,3-DIOXO-1,3-DIHYDRO-2H-ISOINDOL-2-YL)ETHOXYL]-3-OXOBUTANOATE is used as a key intermediate in the synthesis of Amlodipine Besilate (A633500) related compounds. It plays a crucial role in the development of these pharmaceuticals, which are used for the treatment of various cardiovascular conditions, such as hypertension and angina.
As an intermediate in the synthesis of Amlodipine Besilate related compounds, ETHYL4-[2-(1,3-DIOXO-1,3-DIHYDRO-2H-ISOINDOL-2-YL)ETHOXYL]-3-OXOBUTANOATE contributes to the production of medications that help manage and treat cardiovascular diseases, improving the quality of life for patients suffering from these conditions.

Upstream product

• 3891-07-4 N-(2-Hydroxyethyl)phthalimide 
• 638-07-3 ethyl (2-chloroaceto)acetate 
• 623-73-4 diazoacetic acid ethyl ester 
• 81142-14-5 [2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)ethoxy]acetaldehyde 
• 69676-63-7 2-(2-phthalimidoethoxy)ethanol 
• 69676-65-9 2-(2-phthalimidoethoxy)-acetic acid 
• 6148-64-7 ethyl potassium malonate 
• 13176-46-0 4-bromoethyl acetoacetate 
• 1074-82-4 potassium phtalimide 
• 107-07-3 2-chloro-ethanol 
• 85-44-9 phthalic anhydride 

Downstream Products

• 103198-43-2 4-(2,3-Dichloro-phenyl)-2-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethoxymethyl]-6-methyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-isopropyl ester 
• 140171-55-7 4-(2-Chloro-phenyl)-2-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethoxymethyl]-6-methoxymethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester 
• 140171-56-8 4-(2-Chloro-phenyl)-2-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethoxymethyl]-6-methylsulfanylmethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester 
• 140171-57-9 2-tert-Butoxymethyl-4-(2-chloro-phenyl)-6-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethoxymethyl]-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester 
• 120300-92-7 4-(2-chlorophenyl)-5-(2-cyanoethoxycarbonyl)-3-ethoxycarbonyl-6-methyl-2-(2-phtalimidoethoxymethyl)-1,4-dihydropyridine 
• 103198-42-1 4-(2,3-Dichloro-phenyl)-2-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethoxymethyl]-6-methyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester 
• 103198-44-3 4-(2,3-Dichloro-phenyl)-2-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethoxymethyl]-6-methyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-(2-methoxy-ethyl) ester 
• 140171-52-4 4-(2,3-Dichloro-phenyl)-2-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethoxymethyl]-6-methyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid 5-(2-dimethylamino-ethyl) ester 3-ethyl ester 
• 140171-53-5 4-(2,3-Dichloro-phenyl)-2-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethoxymethyl]-6-methyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid 5-[2-(benzyl-methyl-amino)-ethyl] ester 3-ethyl ester 
• 400024-08-0 ethyl 2-(2-chlorobenzylidene)-4-[(2-phthalimido)ethoxy]acetoacetate 
• 845744-00-5 ethyl 2-{[2-(1,3-dioxoisoindolin-2-yl)ethoxy]methyl}-4-(2-chlorophenyl)-5-cyano-6-methyl-1,4-dihydropyridine-3-carboxylate 
• 88150-62-3 4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-2-[2-phthalimidoethoxymethyl]-1,4-dihydropyridine 
• 1203506-42-6 ethyl 6-chloro-2-(2-phthalimidoethoxy)methyl-4-phenylquinoline-3-carboxylate 
• 88150-47-4 (RS)-amlodipine maleate 

Relevant academic research and scientific papers

Method for preparing amlodipine besylate intermediate by using micro-reaction device

The invention provides a method for producing an amlodipine besylate intermediate by using a micro-reaction device. According to the method, o-chlorobenzaldehyde is used as a raw material, the amlodipine besylate intermediate is rapidly and safely prepared by using the micro-reaction device, and the method has the advantages of high reaction conversion rate, simple post-treatment, small reaction volume, short reaction time, low energy consumption and the like, and has relatively high commercial value.

Preparation method of amlodipine intermediate

The invention provides a preparation method of an amlodipine intermediate, belonging to the technical field of bulk drug synthesis. The preparation method comprises the following steps: mixing a compound 1 (2-(2-(2-hydroxyethoxy)ethyl)isoindoline-1,3-dione), an N-O free radical catalyst, a metal salt catalyst and a first organic solvent, and carrying out an oxidation reaction under the action of an oxidizing agent to obtain a compound 2, wherein the oxidizing agent is air or oxygen; mixing the compound 2, an acylating chlorination reagent and a second organic solvent, and carrying out an acylating chlorination reaction to obtain a compound 3; and mixing the compound 3, monopotassium malonate, tertiary amine and a third organic solvent, and carrying out a C-acylation reaction to obtain theamlodipine intermediate. The method provided by the invention has the advantages of usage of cheap and easily available raw materials, less three-waste pollution, high process safety, simplicity and convenience in operation and easiness in industrial production.

Preparation method of amlodipine key intermediate

The invention discloses a preparation method of an amlodipine key intermediate, which relates to the field of drug synthesis. The preparation method comprises the following specific steps of reactinga compound 3 (2-(2-(2-hydroxyethoxy) ethyl) isoindoline-1, 3-diketone) with DMSO (dimethyl sulfoxide) and oxalyl chloride to obtain a compound 2 (2-(2-(1, 3-dioxaisoindoline-2-yl) ethoxy) acetaldehyde), then, enabling the compound 2 and ethyl diazoacetate to be subjected to a C-H bond insertion reaction under the catalysis of Lewis (Lewis) acid, and acquiring a compound 1 ((2-(1, 3-dioxaisoindoline-2-yl) ethoxy)-3-oxabutyrate). According to the preparation method, a NaH route commonly adopted in current production is avoided, the total yield is equivalent to that of the NaH route, and the rawmaterials are cheaper and easier to obtain, so that the safety and the production efficiency are greatly improved, the total cost is reduced by about 30%, and the preparation method is suitable for industrial production.

Synthesis technology of amlodipine maleate

The invention discloses a synthesis technology of amlodipine maleate and relates to the technical field of medicine synthesis, aiming at solving the problem in an existing synthesis technology that more byproducts and impurities exist in industrial production. By controlling parameters of the synthesis technology and reducing the content of the impurities, the purity of the prepared amlodipine maleate reaches 99.5 percent; the self-made amlodipine maleate is used as a raw material for further preparing the amlodipine maleate, so that the cost of a product is reduced and the quality controllability of the product is strong.

Synthesis process of amlodipine besylate

The invention discloses a synthesis process of amlodipine besylate, relates to the technical field of medicine synthesis and solves the problems of low product purity and poor product quality controllability of products prepared by the existing synthesis process. According to the synthesis process, phthalic anhydride is used as raw materials; the parameters of the synthesis process are controlled;the technical flow process is shortened; the synthesis cost is reduced; the product yield is as high as 91 percent; the purity of the prepared amlodipine besylate is as high as 99.5 percent. The self-made amlodipine besylate are used as raw materials for further preparing the amlodipine besylate tablets; the product cost is reduced; the product quality controllability is high.

Method for synthesizing phthaloyl amlodipine

The invention relates to the field of drug synthesis, particularly to a method for synthesizing phthaloyl amlodipine. The method for synthesizing the phthaloyl amlodipine comprises the following steps: (1) synthesis of N-hydroxyethyl phthalimide; (2) synthesis of ethyl-4-(2-phthaloyl ethoxy) ethyl acetoacetate, wherein the ethyl-4-(2-phthaloyl ethoxy) ethyl acetoacetate is prepared by enabling the N-hydroxyethyl phthalimide to react with 4-chloroacetoacetate under a certain condition; (3) synthesis of phthaloyl amlodipine, wherein a target product is obtained by adding 2-chlorobenzaldehyde, acetic acid, piperidine and beta-methyl aminocrotonate to the ethyl-4-(2-phthaloyl ethoxy) ethyl acetoacetate in sequence under a certain condition to react with the ethyl-4-(2-phthaloyl ethoxy) ethyl acetoacetate, adding acetic acid to a reaction product after the reaction, and crystallizing, filtering, washing and drying the reaction product and the acetic acid. The method for synthesizing the phthaloyl amlodipine, provided by the invention, is efficient and easy to operate and can prepare the phthaloyl amlodipine with high yield and excellent quality.

PROCESS FOR PREPARING AMLODIPINE

A process for preparing phthalimidoamlodipine, which is useful as an intermediate for the preparation of amlodipine and its salts.

COMPOUNDS WITH COMBINED CALCIUM CHANNEL BLOCKER AND β-ADRENERGIC ANTAGONIST OR PARTIAL AGONIST ACTIVITIES FOR TREATMENT OF HEART DISEASE

The present invention provides compounds possessing inhibitory activity against β-adrenergic receptors and L-type calcium channels. The present invention further provides pharmaceutical compositions comprising such compounds, methods of preparing such compounds, and methods of using such compounds for regulating calcium homeostasis, for treating a disease, disorder or condition in which disregulation of calcium homeostasis is implicated, and for treating hypertension, cardiovascular disease, congestive heart failure, myocardial ischemia, cardiomyopathies, stroke or epilepsy.

DIHYDROPYRIDINE COMPOUNDS FOR TREATING OR PREVENTING METABOLIC DISORDERS

This invention relates to dihydropyridine compounds of formula: (I) or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof wherein A2, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, and m are defined herein, and compositions comprising such compounds. The invention also relates to methods of preventing or treating metabolic disorders, such as diabetes mellitus, and conditions and complications associated with diabetes mellitus, comprising administering to a subject in need thereof a compound of formula (I) or a composition comprising such a compound. The invention further relates to kits comprising a compound of formula (I).

ISOLATION OF DIHYDROPYRIDINE DERIVATIVE AND PREPARATION SALTS THEREOF

The title compound is isolated in pure form by using a crystallization process and converted to its pharmaceutically acceptable salts. The crystallization process affects stability and purity of the amlodipine salts. All known impurities and one unknown impurity, which forms during the synthesis of the amlodipine salts, were isolated, characterized, and synthesized. A new method allowing the quantitative HPLC analysis of all related impurities of amlodipine salts in a single chromatogram was developed.