- A preparation method of Ranolazine
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The present invention relates to the technical field of ranolazine, in particular to a ranolazine preparation method, the method comprises the following steps: piperazine through the hydroformylation reaction to obtain the 1 - formyl piperazine, then with 2 - chloro - N - (2, 6 - dimethyl-phenyl) acetamide for carrying out the alkylation reaction to obtain N - (2, 6 - dimethyl-phenyl) - 2 - (4 - formyl piperazine) acetamide, then through hydrolytic reaction to obtain N - (2, 6 - dimethyl-phenyl) - 2 - (1 - piperazinyl) acetamide, finally with 2 - (2 - methyl-phenoxymethyl) oxirane ring opening reaction to obtain the ranolazine. The invention preparation of the ranolazine purity is good, high yield.
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Paragraph 0038; 0041; 0045; 0046; 0049; 0050; 0053
(2019/03/28)
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- NOVEL PROCESS FOR THE PREPARATION OF RANOLAZINE
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The present invention relates to novel processes for the preparation of Ranolazine (I) and its acid addition salts and the novel process for the preparation of compound of formula (7).
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Page/Page column 18; 19
(2016/09/26)
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- In silico approach towards lipase mediated chemoenzymatic synthesis of (S)-ranolazine, as an anti-anginal drug
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An in silico modelling based biocatalytic approach for the synthesis of drugs and drug intermediates in enantiopure forms is a rationalized methodology over the organo-chemical routes. In this study, enzyme-ligand based docking was carried out using (RS)-ranolazine, as the model drug for the screening of a suitable biocatalyst for the kinetic resolution of the racemic drug. The differential interaction of the two enantiomers with the lipase was analyzed on the basis of docking score and H-bond interaction with the amino acid residues, which helped to define the trans-esterification mechanism. Ranolazine [N-(2,6-dimethylphenyl)-2-[4-(2-hydroxy)-3-(2-methoxyphenoxy)propylpiperazin-1-yl]acetamide], an anti-anginal drug, significantly reduces the frequency of anginal attack and has also been used for the treatment of ventricular arrhythmias, and bradycardia. Various lipases were examined via computational as well as wet lab screening and Candida antartica lipase in the form of CLEA was the most efficient one for the (S)-selective kinetic resolution of (RS)-ranolazine, with highest conversion and enantiomeric excess. This is the first report of the chemo-enzymatic synthesis of (S)-ranolazine where the whole drug molecule was used for lipase catalysis. The present study showed that the combination of in silico studies and a classical wet lab approach could change the paradigm of biocatalysis.
- Sawant, Ganesh,Ghosh, Saptarshi,Banesh, Sooram,Bhaumik, Jayeeta,Chand Banerjee, Uttam
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p. 49150 - 49157
(2016/06/09)
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- Process for the Preparation of Ranolazine
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A process for the preparation of ranolazine comprises the step of condensing N-(2,6-dimethylphenyl)-1-piperazinyl acetamide with a compound of formula (I) to obtain ranolazine, in which X is chlorine or bromine Ranolazine is prepared by condensing ring-opening halide which replaces epoxide in this process.
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Paragraph 0047; 0048; 0049; 0050
(2013/04/13)
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- "All water chemistry" for a concise total synthesis of the novel class anti-anginal drug (RS), (R), and (S)-ranolazine
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A novel strategy of 'all water chemistry' is reported for a concise total synthesis of the novel class anti-anginal drug ranolazine in its racemic (RS) and enantiopure [(R) and (S)] forms. The reactions at the crucial stages of the synthesis are promoted by water and led to the development of new water-assisted chemistries for (i) catalyst/base-free N-acylation of amine with acyl anhydride, (ii) base-free N-acylation of amine with acyl chloride, (iii) catalyst/base-free one-pot tandem N-alkylation and N-Boc deprotection, and (iv) base-free selective mono-alkylation of diamine (e.g., piperazine). The distinct advantages in performing the reactions in water have been demonstrated by performing the respective reactions in organic solvents that led to inferior results and the beneficial effect of water is attributed to the synergistic electrophile and nucleophile dual activation role of water. The new 'all water' strategy offers two green processes for the total synthesis of ranolazine in two and three steps with 77 and 69% overall yields, respectively, and which are devoid of the formation of the impurities that are generally associated with the preparation of ranolazine following the reported processes.
- Kommi, Damodara N.,Kumar, Dinesh,Chakraborti, Asit K.
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p. 756 - 767
(2013/03/29)
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- An efficient protocol for regioselective ring opening of epoxides using sulfated tungstate: Application in synthesis of active pharmaceutical ingredients atenolol, propranolol and ranolazine
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Sulfated tungstate was found to be a new and highly efficient catalyst for opening of epoxide rings by amines to give β-amino alcohols with high regioselectivity. Various advantages associated with this novel and environmental friendly protocol include solvent-free conditions, short reaction times, high product yields, simple workup procedure and easy recovery and reusability of the catalyst. This protocol has been applied for the synthesis of active pharmaceutical ingredients atenolol, propranolol and ranolazine.
- Pathare, Sagar P.,Akamanchi, Krishnacharya G.
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p. 6455 - 6459
(2013/11/19)
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- An efficient synthesis of 1-(2-Methoxyphenoxy)-2,3-epoxypropane: Key intermediate of β-adrenoblockers
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An efficient process for the preparation of 1-(2-methoxyphenoxy)-2,3- epoxypropane, a key intermediate for the synthesis of ranolazine is described.
- Madivada, Lokeswara Rao,Anumala, Raghupathi Reddy,Gilla, Goverdhan,Kagga, Mukkanti,Bandichhor, Rakeshwar
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p. 1660 - 1664
(2013/02/25)
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- Improved process for ranolazine: An antianginal agent
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An improved process has been developed for the active pharmaceutical ingredient, ranolazine with 99.9% purity and 47% overall yield (including three chemical reactions and one recrystallization). Formation and control of all the possible impurities is described. All the solvents used in the process were recovered and reused. The unreacted piperazine is recovered as piperazine monophosphate monohydrate salt.
- Aalla, Sampath,Gilla, Goverdhan,Anumula, Raghupathi Reddy,Kurella, Srinivas,Padi, Pratap Reddy,Vummenthala, Prabhakar Reddy
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p. 748 - 754
(2012/08/27)
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- Combination therapy for the prevention of statin induced diabetes
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Novel combinations comprising HMG CoA reductase inhibitors, or statins, with partial fatty acid oxidation inhibitors (pFOXi), and methods for their use, are disclosed. These combinations are useful in preventing or reducing the risk of developing diabetes which results from therapy with a statin.
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- PREPARATION OF RANOLAZINE, ITS SALTS AND INTERMEDIATES THEREOF
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The present patent application relates to an improved process for the preparation of Ranolazine, pharmaceutically acceptable salts and intermediates thereof. Specifically it relates to processes for preparation of 1-(2-methoxy phenoxy)-2,3-epoxy propane in substantially aqueous solvent medium and 2-chloro-N-(2,6-dimethylphenyl) acetamide without using any additional base, which are intermediates, useful in the preparation of Ranolazine and pharmaceutically acceptable salts thereof.
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Page/Page column 17
(2010/04/06)
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- PREPARATION OF RANOLAZINE
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Preparation of ranolazine and intermediates thereof, for use in pharmaceutical compositions comprising ranolazine.
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Page/Page column 52
(2010/04/06)
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- HIGHLY PURE RANOLAZINE OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
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Provided herein is an impurity of ranolazine, l-[4-[2-hydroxy-3-(2-methoxy-phenoxy)- propyl]-piperazin-l-yl]-3-(2-methoxy-phenoxy)-propan-2-ol (dimer impurity-3), and process for preparing and isolating thereof. Provided further herein is a highly pure ranolazine or a pharmaceutically acceptable salt thereof substantially free of dimer impurity-3, process for the preparation, and pharmaceutical compositions comprising highly pure ranolazine or a pharmaceutically acceptable salt thereof substantially free of dimer impurity-3.
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Page/Page column 19
(2010/04/30)
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- A PROCESS FOR THE PREPARATION OF RANOLAZINE
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The present invention relates to an improved and novel process for preparation of ranolazine.
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Page/Page column 9
(2010/09/17)
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- Synthesis of ranolazine metabolites and their anti-myocardial ischemia activities
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The anti-anginal drug Ranolazine, a partial fatty acid oxidation (pFOX) inhibitor, is thought to modulate the metabolism during myocardial ischemia by activating pyruvate dehydrogenase activity to promote glucose oxidation. Ranolazine and its five principal metabolites: CVT-2512, CVT-2513, CVT-2514, CVT-2738 and CVT-4786, were synthesized. The effect of Ranolazine and its metabolites on the ECG (electrocardiogram) of mice with myocardial ischemia induced by isoprenaline and their effect on alleviating the symptom of myocardial ischemia were tested and compared. The results showed that CVT-2738 and CVT-2513 could be protective against mice myocardial ischemia induced by isoprenaline. Within all the metabolites tested in this study, CVT-2738 exhibited the best potency, however, it was still less potent than Ranolazine.
- Yao, Zhangyu,Gong, Shubo,Guan, Teng,Li, Yunman,Wu, Xiaoming,Sun, Hongbin
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experimental part
p. 1218 - 1222
(2010/06/16)
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- PROCESS FOR PREPARING A PIPERAZINE DERIVATIVE
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Disclosed is a process for preparing purified ranolazine of formula (I), which is indicated for the chronic treatment of angina, comprising reacting 1-[(2,6-dimethylphenyl)aminocarbonyl]piperazine with 1-phenoxy-2,3-epoxypropane in an inert solvent followed by precipitating the ranolazine.
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Page/Page column 4
(2009/12/28)
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- SUBSTITUTED PIPERAZINES
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Disclosed herein are substituted piperazine late Na+ channel modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.
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Page/Page column 31-32
(2009/01/24)
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- IMPROVED PROCESS FOR THE PREPARATION OF RANOLAZINE
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The present invention provides an improved process for the preparation of ranolazine of formula I and pharmaceutically acceptable salts thereof, by reacting 2,6-dimethylaniline derivative with chloroacetyl chloride in the presence of base in water and resulting amide intermediate is reacted with piperazine and the resulting piperazinc derivative is further condensed with an appropriate oxirane derivative ( prepared by the reaction of 2-methoxyphenol with epichlorohydrin in the presence of base using phase transfer catalyst) in an inert solvent, and highly pure ranolazine is isolated and converted to its acid salts using excess of mineral acid.
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Page/Page column 13; 15
(2008/12/05)
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- CRYSTALLINE AND AMORPHOUS FORM OF RANOLAZINE AND THE PROCESS FOR MANUFACTURING THEM
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Process for the preparation of novel crystalline and amorphous form of (±)-1-[3-(2-Methoxyphenoxy)-2-hydroxypropyl]-4-[N-(2,6-dimethylphenyl)carbamoylmethyl] piperazine dihydrochloride & a crystalline form of Ranolazine base is disclosed in the present invention which has the formula (I) and is a medicine useful as anti-anginal agent.
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Page/Page column 7; 8
(2008/06/13)
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- NMR study on (±)-1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-[(2,6- dimethylphenyl)aminocarbonylmethyl]piperazine dihydrochloride salt
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(±)-1-[3-(2-Methoxyphenoxy)-2-hydroxypropyl]-4-[(2,6-dimethylphenyl) aminocarbonylmethyl]piperazine dihydrochloride salt was studied spectroscopically. Complete NMR assignments for dihydrochloride salt were made using DEPT, H-H COSY, as well as HMQC and HMBC heteronuclear correlation techniques.
- Qin, Bingjie,Lin, Jimao,Lin, Zhenguang,Xue, Yun,Ren, Huixue
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p. 665 - 671
(2007/10/03)
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