142387-99-3

Basic information

• Product Name: Ranolazine
• Synonyms: Ranolazine intermediate
• CAS NO: 142387-99-3
• Molecular Formula: C24H33N3O4
• Molecular Weight: 427.542
• Mol File: 142387-99-3.mol

Chemical Properties

• Boiling Point: 624.1°C at 760 mmHg
• Flash Point: 331.2°C
• Appearance: /
• Density: 1.174g/cm³
• Vapor Pressure: 1.94E-16mmHg at 25°C
• Refractive Index: 1.585
• Storage Temp.: RT
• Solubility: Soluble in DMSO (up to 25 mg/ml) or in Ethanol (up to 20 mg/ml).
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 1 month.
• CAS DataBase Reference: Ranolazine(CAS DataBase Reference)
• NIST Chemistry Reference: Ranolazine(142387-99-3)
• EPA Substance Registry System: Ranolazine(142387-99-3)

Safety Data

• Hazardous Substances Data: 142387-99-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Ranolazine is used as a therapeutic agent for the treatment of chronic angina. It helps alleviate the symptoms of this condition by improving the efficiency of the heart's energy use and reducing the oxygen demand of the heart muscle.
Additionally, Ranolazine is used in combination with other medications such as amlodipine, beta-blockers, or nitrates to enhance the overall treatment efficacy for patients suffering from chronic angina. This combination approach aims to provide better management of the condition and improve the patient's quality of life.

References

1) Belardinelli?et al., (2006),?Inhibition of the late sodium current as a potential cardioprotective principle: effects of the late sodium current inhibitor ranolazine; Heart,?92?iv6 2) Wang?et al. (2008),?State- and Use-Dependent Block of Muscle Nav1.4 and Neuronal Nav1.7 Voltage-Gated Na+-Channel Isoforms by Ranolazine; Mol. Pharmacol.?73?940 3) Rajamani?et al., (2008),?Block of tetrodotoxin-sensitive, Na(V)1.7 and tetrodotoxin-resistant, Na(V)1.8, Na+ channels by ranolazine; Channels(Austin)?2?449

InChI:InChI=1/C24H33N3O4/c1-18-7-6-8-19(2)24(18)25-23(29)16-27-13-11-26(12-14-27)15-20(28)17-31-22-10-5-4-9-21(22)30-3/h4-10,20,28H,11-17H2,1-3H3,(H,25,29)

Upstream product

• 5294-61-1 N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide 
• 162712-35-8 CVT-2513 
• 1131-01-7 2-chloro-N-(2,6-dimethylphenyl)acetamide 
• 2210-74-4 2-(2-methoxy-phenoxymethyl)-oxirane 
• 90-05-1 2-methoxy-phenol 
• 87-62-7 2,6-dimethylaniline 
• 1427177-23-8 (RS)-2-(4-(3-chloro-2-hydroxyphenyl)piperazin-1-yl)-N-(2,6-dimethylphenyl)acetamide 
• 25772-81-0 1-chloro-3-(2-methoxyphenoxy)-2-propyl alcohol 
• 110-85-0 piperazine 
• 95635-55-5 Ranolazine 
• 108-05-4 vinyl acetate 

Relevant articles and documents

NMR study on (±)-1-[3-(2-methoxyphenoxy)-2-hydroxypropyl]-4-[(2,6- dimethylphenyl)aminocarbonylmethyl]piperazine dihydrochloride salt

(±)-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.

An efficient synthesis of 1-(2-Methoxyphenoxy)-2,3-epoxypropane: Key intermediate of β-adrenoblockers

An efficient process for the preparation of 1-(2-methoxyphenoxy)-2,3- epoxypropane, a key intermediate for the synthesis of ranolazine is described.

A preparation method of Ranolazine

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.

In silico approach towards lipase mediated chemoenzymatic synthesis of (S)-ranolazine, as an anti-anginal drug

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.

NOVEL PROCESS FOR THE PREPARATION OF RANOLAZINE

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).

Nanocellulose derivative/silica hybrid core-shell chiral stationary phase: Preparation and enantioseparation performance

Core-shell silica microspheres with a nanocellulose derivative in the hybrid shell were successfully prepared as a chiral stationary phase by a layer-by-layer self-assembly method. The hybrid shell assembled on the silica core was formed using a surfactant as template by the copolymerization reaction of tetraethyl orthosilicate and the nanocellulose derivative bearing triethoxysilyl and 3,5-dimethylphenyl groups. The resulting nanocellulose hybrid core-shell chiral packing materials (CPMs) were characterized and packed into columns, and their enantioseparation performance was evaluated by high performance liquid chromatography. The results showed that CPMs exhibited uniform surface morphology and core-shell structures. Various types of chiral compounds were efficiently separated under normal and reversed phase mode. Moreover, chloroform and tetrahydrofuran as mobile phase additives could obviously improve the resolution during the chiral separation processes. CPMs still have good chiral separation property when eluted with solvent systems with a high content of tetrahydrofuran and chloroform, which proved the high solvent resistance of this new material.

"All water chemistry" for a concise total synthesis of the novel class anti-anginal drug (RS), (R), and (S)-ranolazine

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.

An efficient protocol for regioselective ring opening of epoxides using sulfated tungstate: Application in synthesis of active pharmaceutical ingredients atenolol, propranolol and ranolazine

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.

Process for the Preparation of Ranolazine

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.

Improved process for ranolazine: An antianginal agent

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.