167221-71-8

Basic information

• Product Name: Clevidipine butyrate
• Synonyms: Methyl (1-oxobutoxy)methyl 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dime thyl-3,5-pyridinedicarboxylate;4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-Pyridinedicarboxylic acid methyl (1-oxobutoxy)methyl ester;Clevidipine butyrate;Cleviprex;3,5-Pyridinedicarboxylicacid, 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-, 3-methyl5-[(1-oxobutoxy)methyl] ester;Clevidipine Butyrate/Cleviprex;4-(2,3-Dichlorophenyl)-1,4-dihydro-2,6-diMethyl-3,5-pyridinedicarboxylic Acid 3-Methyl 5-[(1-Oxobutoxy)Methyl] Ester;Clevelox
• CAS NO: 167221-71-8
• Molecular Formula: C21H23Cl2NO6
• Molecular Weight: 456.32
• EINECS: 1312995-182-4
• Product Categories: Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Clevidipine Butyrate impurity;Cardiovascular APIs
• Mol File: 167221-71-8.mol

Chemical Properties

• Melting Point: 128-130°C
• Boiling Point: 539.7 °C at 760 mmHg
• Flash Point: 280℃
• Appearance: Powder
• Density: 1.289
• Storage Temp.: Refrigerator
• Solubility: ≥21.4 mg/mL in DMSO; insoluble in H2O; ≥7.45 mg/mL in EtOH with ultrasonic
• PKA: 2.45±0.70(Predicted)
• Water Solubility: Insoluble in water
• CAS DataBase Reference: Clevidipine butyrate(CAS DataBase Reference)
• NIST Chemistry Reference: Clevidipine butyrate(167221-71-8)
• EPA Substance Registry System: Clevidipine butyrate(167221-71-8)

Safety Data

• Safety Statements: 24/25
• Hazardous Substances Data: 167221-71-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Clevidipine butyrate is used as an oral antihypertensive agent for the treatment of hypertension in patients who require long-term blood pressure control.
Used in Emergency Medicine:
Clevidipine butyrate is used as an intravenous, short-acting calcium channel blocker for quick and accurate control of blood pressure in emergency settings. It is particularly useful in situations where rapid blood pressure reduction is necessary, such as in cardiac surgical settings, intensive care units, and emergency departments.
Used in Cardiac Surgery:
Clevidipine butyrate is used as a calcium channel protein inhibitor and blocker during cardiac surgery to manage hypertension and maintain stable blood pressure levels.

Originator

AstraZeneca (United Kingdom)

Side effects

Clevidipine is contraindicated in patients with severe aortic stenosis, defective lipid metabolism, and allergies to eggs, egg products, soybeans, or soy products. The chemical synthesis of clevidipine entails the esterification of 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid monomethyl ester with chloromethyl butyrate by the action of potassium bicarbonate in refluxing acetonitrile.

Synthesis

The chemical synthesis of clevidipine entails the esterification of 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid monomethyl ester with chloromethyl butyrate by the action of potassium bicarbonate in refluxing acetonitrile. The DHP-monoester starting material is obtained in two steps through condensation of methyl 2,3-dichlorobenzylidine acetoacetate and 2-cyanoethyl ester of 2-amino-2-propenoic acid to the DHP diester, followed by base catalyzed cleavage of the cyanoethyl group. Clevidipine is practically insoluble in water and is formulated in an oil-inwater emulsion.

InChI:InChI=1/C21H23Cl2NO6/c1-5-7-15(25)29-10-30-21(27)17-12(3)24-11(2)16(20(26)28-4)18(17)13-8-6-9-14(22)19(13)23/h6,8-9,18,24H,5,7,10H2,1-4H3

Upstream product

• 33657-49-7 chloromethyl n-butyrate 
• 1020718-27-7 2-(2',3'-dichloro-benzylidene)-3-oxo-butyric acid butyryloxymethyl ester 
• 14205-39-1 methyl 3-aminocrotonate 
• 6334-18-5 2,3-dichlorobenzylaldehyde 
• 1346550-30-8 benzylidine tert-butyl ester 
• 404373-25-7 2-acetyl-3-(2',3'-dichlorophenyl)prop-2-enoic acid 
• 105-45-3 acetoacetic acid methyl ester 
• 108-20-3 di-isopropyl ether 
• 123853-39-4 (+)-4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-3-pyridinecarboxylic acid 

Relevant articles and documents

Butyric acid clevidipine preparation method

The invention discloses a preparation method of clevidipine butyrate, comprising the following steps: (1) carrying out one-pot reaction by putting 2,3-dichlorobenzaldehyde, methyl acetoacetate and 3-amino crotonic acid ethyl cyanide in a solvent under the action of a catalyst; (2) carrying out recrystallization to obtain a pure product (+/-)-3-(2-cyanoethyl)-5-methyl-4-(2',3'-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid; (3) carrying out a reaction between the pure product and alkali; (4) adding water and hydrochloric acid, and collecting an intermediate from reaction products; and (5) carrying out a reaction between the intermediate and n-chloromethyl butyrate in the presence of an alkaline substance and an iodide catalyst, and finally collecting the target product clevidipine butyrate from reaction products. The preparation method provided by the invention has advantages of high yield, stable product quality and low cost, is simple to operate, and is suitable for industrial product of clevidipine butyrate.

Butyric acid clevidipine synthetic method

The invention discloses a synthetic method of cleviprex. The method comprises the following steps: reacting a compound 1 with a compound 2 in the presence of tetrahydrofuran and triethylamine to generate a compound 3, dissolving the compound 3, a compound

PROCESS FOR PREPARATION OF CLEVIDIPINE AND ITS INTERMEDIATE

The present invention relates to a process for the removal of t-butyl group from t-butyl methyl 4-(2',3'-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate to provide-1,4-dihydro-2,6-dimethyl-4-(2',3'-dichorophenyl)-5-methoxycarbonyl-3-pyr

Preparation of dihydropyridines

The invention relates to a novel method and novel compounds for the preparation of clevidipine butyrate, a very short acting hypertensive calcium antagonist, as well as the synthesis of these new compounds useful for the preparation of clevidipine (also k

PREPARATION OF INTERMEDIATES FOR THE SYNTHESIS OF DIHYDROPYRIDINE CALCIUM CHANNEL BLOCKERS

4- (2,3- dichlorophenyl) -1,4- dihydro- 2,6- dimethyl- 5- methoxycarbonyl- 3- pyridinecarboxylic acid, a key intermediate in the synthesis of the cardiovascular calcium channel blocker drug 3-butanoyloxymethoxycarbonyl-5- methoxycarbonyl-4- (2,3-dichlorop

PREPARATION OF CLEVIDIPINE BUTYRATE

The current application relates to a process for preparing O3-(butanoyloxymethyl)-O5-methyl-4-(2, 3-dichlorophenyl)-2,6-dimethyl-1,4- dihydropyridme-3,5-dicarboxylate, clevidipine butyrate, by alkylation of 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-

PREPARATION OF DIHYDROPYRIDINES

The invention relates to a method and compounds for the preparation of clevidipine butyrate, a very short acting hypertensive calcium antagonist, as well as the synthesis of these compounds useful for the preparation of clevidipine (also known as clevidip

Manufacturing process

A method for the manufacture of clevidipine by reaction of an inorganic salt of 4-(2′,3′-dichlorophenyl)-1,4-dihydro-5-methoxycarbonyl-2,6-dimethyl-3-pyridine-carboxylate and chloro methyl butyrate.

SHORT-ACTING DIHYDROPYRIDINES

Compounds of the general formula wherein R1 and R2 are independently selected from the group consisting of hydrogen, chloro, bromo, nitro, cyano, trifluoromethyl, and R3 and R4 are independently selected from straight or branched lower (1-5 carbon atoms)

Pharmaceutical emulsion

A pharmaceutical emulsion for intravenous administration is disclosed which comprises a) a short acting dihydropyridine compound; b) a lipid phase; c) an emulsifier and d) water or a buffer.