- Method for preparing amlodipine besylate intermediate by using micro-reaction device
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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.
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- Synthesis process of amlodipine besylate
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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.
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Paragraph 0006; 0014; 0015; 0017; 0023-0026
(2018/09/14)
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- Synthesis technology of amlodipine maleate
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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.
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Paragraph 0013; 0019-0021
(2018/09/08)
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- Method for synthesizing phthaloyl amlodipine
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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.
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Paragraph 0035; 0036; 0037
(2017/07/21)
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- Using the new crystal form [...] and production of high-purity [...]
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PROBLEM TO BE SOLVED: To provide a process for producing high-purity phthaloyl amlodipine for synthesis of an amlodipine besilate having excellent purity as a medicine.SOLUTION: Provided are TW-A type and TW-B type crystal forms of highly pure phthaloyl amlodipine. In powder X-ray diffraction, the TW-A type phthaloyl amlodipine has diffraction peaks at 2θ(°)=8.7±0.2, 11.0±0.2, 13.4±0.2, 15.7±0.2, and 24.6±0.2. In powder X-ray diffraction, the TW-B type phthaloyl amlodipine has diffraction peaks at 2θ(°)=6.6±0.2, 9.9±0.2, 11.1±0.2, 17.3±0.2, and 24.4±0.2.
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Paragraph 0005; 0069; 0070
(2017/02/17)
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- Acetone solvate of phthaloyl amlodipine
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The present invention is directed to an acetone solvate of phthaloyl amlodipine, its use in the synthesis of amlodipine and a process for its preparation which comprises dissolving phthaloyl amlodipine in acetone and cooling the mixture.
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Page/Page column 8
(2008/12/07)
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- ACETONE SOLVATE OF PHTHALOYL AMLODIPINE
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An acetone solvate of phthaloyl amlodipine, as well as a process for its preparation including dissolving phthaloyl amlodipine in acetone and cooling the mixture. The present invention also comprises a method for the synthesis of amlodipine, its salts or solvates, which comprises the use of an acetone solvate of phthaloyl amlodipine.
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Page/Page column 4
(2008/12/07)
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- PROCESS FOR PREPARING AMLODIPINE
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A process for preparing phthalimidoamlodipine, which is useful as an intermediate for the preparation of amlodipine and its salts.
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Page/Page column 6-7
(2010/11/28)
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- PROCESS FOR THE PREPARATION OF PURE AMLODIPINE
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The present invention relates to an improved process for the preparation of pure Amlodipine via the effective purification of phthalimido Amlodipine (3-ethyl-5-methyl -2-[(2-phthalimido ethoxy) methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-dicarboxylate).
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Page/Page column 6; 7
(2008/06/13)
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- Process for the preparation of anti-ischemic and anti-hypertensive drug amlodipine besylate
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Process for the preparation of anti-ischemic and anti-hypertensive drug amlodipine besylate [2-{(2-aminoethoxy)-methyl-4-(2-chlorophenyl) 3-ethoxy carbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine} benzene sulphonate]. Phthalic anhydride is condensed with monoethanol amine at 150-190° C. The resulting N-(2-hydroxyethyl) phthalimide is coupled with 4-chloroethyl acetoacetate in the presence of sodium hydride in an organic solvent in an inert atmosphere at ?11 to ?15° C. Ethyl-4-[-2(phthalimido) ethoxy] acetoacetate formed is coupled with orthochloro benzaldehyde in the presence of pyridine salt at 70-90° C. Ethyl-2-(2-chloro benzylidine)4-[-2(phthalimido) ethoxy] acetoacetate fanned is condensed with methyl amino crotonate at 20-40° C. in the presence of acetic acid to form phthaloyl amlodipine [2-(2-Phthalimidoethoxy) methyl-3-carboethoxy 1(chlorophenyl)-S-carbomethoxy-6-methyl-1,4-dihydropyridin] which is purified by dissolving in an organic solvent in the ratio 1:2-1:5 w/v and precipitated by the addition of water at 35-60° C. Purified phthaloyl amlodipine is hydrolysed with methylamine in the presence of a protic solvent at 20-50° C. Amlodipine base [2-(aminoethoxy) methyl-3-carboethoxy-4-(2-chlorophenyl)-5-carbomethoxy-6-methyl-1,4-dihydropyridin] formed is reacted with benzene sulfonic acid. The resulting amlodipine besylate is purified in an organic solvent at 30-70° C. and precipitated by the addition of an insoluble solvent.
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- Process for making amlodipine
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Amlodipine and related analogues thereof are prepared by the following general reaction scheme: R1and R2each independently represent a C1-C4alkyl group. The process provides for the formation of compounds of formula (1) in good yield and purity. Further, the compounds of formula (1) can be used as calcium channel blockers or as reference standards or reference markers for checking the purity of amlodipine.
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- Intermediate for the synthesis of amlodipine, a process for the preparation there and corresponding use
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An intermediate for the synthesis of amlodipine, a process for the preparation thereof and the corresponding use are disclosed. The intermediate is ethyl 3-amino-4-(2-(phthalimido)ethoxy)crotonate and is of formula III The process for the preparation thereof comprises reacting the acetoacetate of formula with ammonium acetate; and the use thereof is for the preparation of the compound of formula the process being conducted by reacting ethyl 3-amino-4-[2-(phthalimido)ethoxy]crotonate with a benzylidene derivative.
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- Process for making amlodipine, derivatives therof, and precursors therefor
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Amlodipine and related analogues thereof are prepared by the following general reaction scheme: R1 and R2 each independently represent a C1-C4 alkyl group. The process provides for the formation of compounds of formula (1) in good yield and purity. Further, the compounds of formula (1) can be used as calcium channel blockers or as reference standards or reference markers for checking the purity of amlodipine.
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- Dihydropyridines
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Dihydropyridine anti-ischaemic agents of the formula: STR1 and their salts where R is aryl or heteroaryl, R1 and R2 are each C1 -C4 alkyl or 2-methoxyethyl, Y is --(CH2)n -- where n is 2, 3, or 4 and is optionally substituted by 1 or 2 CH3 groups, and R3 is an optionally substituted 5- or 6-membered heterocyclic group attached to the adjacent N atom by a C atom, said group R3 being optionally fused to a further heterocyclic group or to a benzene ring.
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- 2-(SECONDARY AMINOALKOXYMETHYL) DIHYDROPYRIDINE DERIVATIVES AS ANTI-ISCHAEMIC AND ANTIHYPERTENSIVE AGENTS
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A dihydropyridine compound of the formula or a pharmaceutically acceptable acid addition salt thereof, wherein Y is -(CH2)2-, -(CH2)3-, -CH2CH(CH3)-or -CH2C(CH3)2-; R is aryl or heteroaryl; R1 and R2 are each independently C1-C4 alkyl or 2-methoxyethyl; and R3 is hydrogen, C1-C4 alkyl, 2-(Ci-C4 alkoxy)ethyl, cyclopropylmethyl, benzyl, or -(CH2)mCOR4 where m is 1, 2 or 3 and R4 is hydroxy, C1-C4 alkoxy or -NR5R6 where R5 and R6 are each independently hydrogen or C1-C4 alkyl can be employed for treating or preventing a heart condition or hypertension.
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