96382-71-7

Basic information

• Product Name: DEHYDRO FELODIPINE-13C4
• Synonyms: DEHYDRO FELODIPINE-13C4;4-(2,3-Dichlorophenyl)-2,6-dimethyl-3,5-pyridinedicarboxylic Acid Ethyl Methyl Ester;H 152/3;H 152/37;4-(2,3-Dichlorophenyl)-2,6-dimethyl-3,5-pyridinedicarboxylic acid 5-ethyl 3-methyl ester;4-(2,3-Dichlorophenyl)-2,6-dimethylpyridine-3,5-dicarboxylic acid 3-ethyl 5-methyl ester;Felodipine EP IMpurity A;3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethylpyridine-3,5-dicarboxylate
• CAS NO: 96382-71-7
• Molecular Formula: C₁₈H₁₇Cl₂NO₄
• Molecular Weight: 382.241
• Product Categories: Various Metabolites and Impurities;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals
• Mol File: 96382-71-7.mol

Chemical Properties

• Melting Point: 70-73C
• Boiling Point: 444.8°Cat760mmHg
• Flash Point: 222.8°C
• Appearance: /
• Density: 1.288g/cm³
• Vapor Pressure: 4.16E-08mmHg at 25°C
• Refractive Index: 1.564
• Storage Temp.: -20°C Freezer
• CAS DataBase Reference: DEHYDRO FELODIPINE-13C4(CAS DataBase Reference)
• NIST Chemistry Reference: DEHYDRO FELODIPINE-13C4(96382-71-7)
• EPA Substance Registry System: DEHYDRO FELODIPINE-13C4(96382-71-7)

Safety Data

• Hazardous Substances Data: 96382-71-7(Hazardous Substances Data)

Usage

InChI:InChI=1/C18H17Cl2NO4/c1-5-25-18(23)14-10(3)21-9(2)13(17(22)24-4)15(14)11-7-6-8-12(19)16(11)20/h6-8H,5H2,1-4H3

Synthetic route

ethyl 2-(2,3-dichlorobenzylidene)-3-oxobutanoate (94739-24-9) + methyl 3-aminocrotonate (14205-39-1) → Dehydrofelodipine (96382-71-7)

Conditions	Yield
In ethanol at 50 - 55℃; for 8h; Darkness; Large scale;	90%

ethyl methyl 1,4-dihydro-2,6-dimethyl-4(2,3-dichlorophenyl)-3,5-pyridinedicarboxylate (72509-76-3) → Dehydrofelodipine (96382-71-7)

Conditions	Yield
With potassium carbonate; eosin Y bis(tetrabutyl ammonium salt) In methanol; water at 20℃; for 12h; Irradiation; Green chemistry;	83%
With potassium carbonate In ethanol; water at 20℃; for 12h;	83.1%
Stage #1: ethyl methyl 1,4-dihydro-2,6-dimethyl-4(2,3-dichlorophenyl)-3,5-pyridinedicarboxylate With hydrogenchloride In water Stage #2: With nickel In water at 20℃; for 4h;	72.4%
With potassium phosphate; ethylenediaminetetraacetic acid; Emulgen 911; human liver cytochrome b5; human liver HL 39 lipid extract; rabbit liver NADPH-P-450 reductase; yeast P-450 IIIA4; magnesium chloride In water Rate constant; other human liver enzymes;

ethyl acetoacetate (141-97-9) + acetoacetic acid methyl ester (105-45-3) + 2,3-dichlorobenzylaldehyde (6334-18-5) → Dehydrofelodipine (96382-71-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: ammonium acetate / ethanol / 2 h / 80 °C 2: eosin Y bis(tetrabutyl ammonium salt); potassium carbonate / water; methanol / 12 h / 20 °C / Irradiation; Green chemistry View Scheme

ethyl acetoacetate (141-97-9) + 2,3-dichlorobenzylaldehyde (6334-18-5) → Dehydrofelodipine (96382-71-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: piperidine; acetic acid / 6 h / 15 - 55 °C / Large scale 2: ethanol / 8 h / 50 - 55 °C / Darkness; Large scale View Scheme

Upstream product

• 141-97-9 ethyl acetoacetate 
• 6334-18-5 2,3-dichlorobenzylaldehyde 
• 94739-24-9 ethyl 2-(2,3-dichlorobenzylidene)-3-oxobutanoate 
• 14205-39-1 methyl 3-aminocrotonate 
• 105-45-3 acetoacetic acid methyl ester 
• 72509-76-3 ethyl methyl 1,4-dihydro-2,6-dimethyl-4(2,3-dichlorophenyl)-3,5-pyridinedicarboxylate 

Relevant articles and documents

Dihydropyridine compound dehydrogenation aromatization method and in use in the drug detection (by machine translation)

Relates to dihydropyridine compound dehydrogenation aromatization method and in use in the drug detection, compounds such as nifedipine, amlodipine, Cini horizontal, Lacidipine, felodipine, NIKA of amlodipine, nitrendipine, nimodipine and BANI to equal, the method in acidic aqueous solution in the presence of a nickel-containing catalyst in the oxidation reaction of the then purified to realize. The method can be used for preparing this kind of drug detection and quality monitoring of the impurity reference substance, also can be used for quality detection process is used in the instrument of the instrument such as the dissolution of the design reference, drug synthesis process and the design of the manufacturing process of the preparation of the reference, in order to avoid impurities introduced by the process channels, in addition can also be dihydropyridine compound of related synthetic process route provides design provides a reference. The reaction can be in the acidic aqueous solution, to a suitable oxidant (such as air) as the oxidizing agent, in the presence of nickel, at normal temperature to carry out dehydrogenation aromatization reaction, mild reaction conditions, the target compound of high conversion rate, the operation is simple, by-product little small pollution to the environment, is a completely environment-friendly preparation process. (by machine translation)

A new process for the preparation of felodipine (by machine translation)

The invention discloses a new process for the preparation of felodipine, including: 1) to acetyl acetic acid methyl ester as the raw material, to prepare the 3 - amino-crotonic acid methyl ester; 2) to 2, 3 - dichloro formaldehyde and acetyl acetic acid ethyl ester as the raw material, to prepare the 2, 3 - two chlorine asia phenmethyl acetyl ethyl acetate; 3) to 2, 3 - two chlorine asia phenmethyl acetyl ethyl acetate, 3 - amino-crotonic acid methyl ester as the raw material, prepare the felodipine. The invention of the preparation process of felodipine, intermediates for the preparation of 3 - amino-crotonic acid methyl ester having a melting point of 83 - 35 °C, far higher than the widely used of the intermediate 3 - amino-crotonic acid ethyl ester (33 - 35 °C), therefore the stability can be improved, convenient in a wider temperature conditions production and storage, is more favorable to the industrialized production and application. At the same time, the process high product yield, high purity, step is simple, easy to operate, and has good practicability. (by machine translation)

For 1, 4 - dihydro pyridine compound to prepare the corresponding pyridine compound (by machine translation)

The invention discloses a method for the 1, 4 - dihydro pyridine compound to prepare the corresponding pyridine compound. The method of the invention is: will be 1, 4 - dihydro pyridine compound, eosin Y of the four n-butyl ammonium salt, potassium carbonate is added to the organic solvent with the water in the mixed solvent of stirring and mixing, inject the air in visible light irradiation under the conditions of reaction, to be after the reaction, by adding ethyl acetate, respectively water, saturated ammonium chloride washing, removal of inorganic alkali and adjust the system to subacid, in the organic phase by adding a small amount of activated carbon to remove the pigment, then dried with anhydrous sodium sulfate, turns on lathe does, recrystallize and obtain the corresponding pyridine compound. The method of the invention compared with the prior art has to oxygen in air as the oxidizing agent, is cheap and easy to get; to sunlight as the energy source, so that the industrial production more favorable; catalytic amount of the use of non-metal catalyst, reduces the cost of synthesizing, avoiding the noble metal in the accumulation of drug in the synthesis. (by machine translation)

Metal-free-mediated oxidation aromatization of 1,4-dihydropyridines to pyridines using visible light and air

A metal-free and environmentally friendly aerobic aromatization photosensitized by organic dye eosin Y bis(tetrabutyl ammonium salt) (TBA-eosinY) has been developed. With the aid of K2CO3, the aerobic catalytic system converts 1,4-dihydropyridines to their corresponding pyridine derivatives efficiently under visible light irradiation (λ=450 nm) at room temperature.

Pyridyl compounds and pharmaceutical compositions containing them

The present invention is concerned with new pyridine double esters of formula (I), their acids, and pharmaceutically acceptable salts. These compounds can be obtained by oxydation of the corresponding 1,4-dihydropyridines, and they are useful as cardioprotective agents in pharmaceutical compositions.

Oxidation of dihydropyridine calcium channel blockers and analogues by human liver cytochrome P-450 IIIA4

A series of 21 different 4-substituted 2,6-dimethyl-3-(alkoxycarbonyl)-1,4-dihydropyridines was considered with regard to oxidation to pyridine derivatives by human liver microsomal cytochrome P-450 (P-450). Antibodies raised against P-450 IIIA4 inhibited the microsomal oxidation of nifedipine and felodipine to the same extent, as did cimetidine and the mechanism-based inactivator gestodene. Gestodene was ~ 103 times more effective an inhibitor than cimetidine, on a molar basis. When rates of oxidation of the 1,4-dihydropyridines were compared to each other in different human liver microsomal preparations, all were highly correlated with each other with the exceptions of a derivative devoid of a substituent at the 4-position and an N1-CH3 derivative. A P-450 IIIA4 cDNA clone was expressed in yeast and the partially purified protein was used in reconstituted systems containing NADPH-cytochrome P-450 reductase and cytochrome b5. This system catalyzed the oxidation of all of the 1,4-dihydropyridines except the two for which poor correlation was seen in the liver microsomes. Principal component analysis supported the view that most of these reactions were catalyzed by the same enzyme in the yeast P-450 IIIA4 preparation and in the different human liver microsomal preparations, or by a closely related enzyme showing nearly identical properties of catalytic specificity and regulation. The results indicate that the enzyme P-450 IIIA4 is probably the major human catalyst involved in the formal dehydrogenation of most but not all 1,4-dihydropyridine drugs.