67593-46-8

Usage

Uses

Used in Pharmaceutical Industry:
2-Acetyl-3-(2-chlorophenyl)acrylic acid methyl ester is used as a potential anti-inflammatory and analgesic agent for its ability to inhibit the COX-2 enzyme, which plays a crucial role in the inflammatory process. This makes it a candidate for the treatment of conditions characterized by inflammation and pain, such as arthritis and other inflammatory disorders.
Used in Cancer Research:
In the field of oncology, 2-Acetyl-3-(2-chlorophenyl)acrylic acid methyl ester is studied for its potential role in cancer treatment. Given its inhibitory effect on COX-2, which is often overexpressed in cancer cells and associated with tumor growth and progression, 2-Acetyl-3-(2-chlorophenyl)acrylic acid methyl ester may offer therapeutic benefits in managing cancer-related inflammation and possibly in synergizing with other cancer treatments to enhance their efficacy.
Used in Drug Development:
As a part of drug development, 2-Acetyl-3-(2-chlorophenyl)acrylic acid methyl ester is utilized in the research and design of new pharmaceuticals. Its unique structure and functional groups provide a foundation for the development of novel drugs with improved efficacy, selectivity, and reduced side effects in treating inflammatory and pain-related conditions.

InChI:InChI=1/C12H11ClO3/c1-8(14)10(12(15)16-2)7-9-5-3-4-6-11(9)13/h3-7H,1-2H3/b10-7+

Synthetic route

2-chloro-benzaldehyde (89-98-5) + acetoacetic acid methyl ester (105-45-3) → methyl 2-(2-chlorophenylmethylene)acetoacetate (67593-46-8)

Conditions	Yield
With piperidine; acetic acid In benzene for 4h; Ambient temperature;	84%
With piperidine In tetrahydrofuran for 4h; Inert atmosphere; Reflux;

methanolic dimethylamine + 2-chloro-benzaldehyde (89-98-5) + acetoacetic acid methyl ester (105-45-3) → methyl 2-(2-chlorophenylmethylene)acetoacetate (67593-46-8)

Conditions	Yield
With acetic acid In ethyl acetate; isopropyl alcohol

methyl 2-(2-chlorophenylmethylene)acetoacetate (67593-46-8) → methyl 2-(2-chlorobenzyl)-3-oxobutanoate

Conditions	Yield
With triethylsilane; iron(III) chloride hexahydrate In dichloromethane at 20℃; for 36h; chemoselective reaction;	90%

3-amino-4-(2,2-diethoxy-ethoxy)but-2-enoic acid ethyl ester + methyl 2-(2-chlorophenylmethylene)acetoacetate (67593-46-8) → 4-(2-chlorophenyl)-2-(2,2-diethoxy-ethoxymethyl)-6-methyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (225939-13-9)

Conditions	Yield
In toluene for 26h; Heating / reflux;	75.3%

o-chlorobenzylidene malononitrile (2698-41-1) + methyl 2-(2-chlorophenylmethylene)acetoacetate (67593-46-8) → methyl 4,6-bis(2-chlorophenyl)-5,5-dicyano-2-methyl-1,4,5,6-tetrahydropyridine-3-carboxylate

Conditions	Yield
With ammonium hydroxide In methanol at 20℃; for 4h;	73%

methyl 2-(2-chlorophenylmethylene)acetoacetate (67593-46-8) + 3-amino-2-crotonic acid 2,2-ethylenedioxy propyl ester (86780-81-6) → 4-(2-Chloro-phenyl)-2,6-dimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-methyl ester 5-(2-methyl-[1,3]dioxolan-2-ylmethyl) ester (103785-54-2)

Conditions	Yield
In ethanol Heating;	47%

methyl 2-(2-chlorophenylmethylene)acetoacetate (67593-46-8) + 3-methylaminobut-2-enoic acid methyl ester (13412-12-9, 21759-68-2, 21759-69-3) → dimethyl 4-(2-chlorophenyl)-1,2,6-trimethyl-1,4-dihydropyridine-3,5-dicarboxylate (109329-68-2) + 2-(2-Chloro-phenyl)-4-methyl-6-methylamino-cyclohexa-3,5-diene-1,3-dicarboxylic acid dimethyl ester (109329-69-3)

Conditions	Yield
In benzene for 2h; Heating;	A 36% B 5.2%
In ethanol Heating;	A 5% B n/a

methyl 2-(2-chlorophenylmethylene)acetoacetate (67593-46-8) + acetoacetic acid methyl ester (105-45-3) → 4-(2-chloro-phenyl)-2,6-dimethyl-4H-pyran-3,5-dicarboxylic acid dimethyl ester

Conditions	Yield
With acetic anhydride; zinc(II) chloride Heating;

O-methylisourea hemisulfate (29427-58-5) + methyl 2-(2-chlorophenylmethylene)acetoacetate (67593-46-8) → methyl 6-(2-chlorophenyl)-2-methoxy-4-methyl-1,6-dihydropyrimidine-5-carboxylate + methyl 6-(2-chlorophenyl)-2-methoxy-4-methyl-3,6-dihydropyrimidine-5-carboxylate

Conditions	Yield
With sodium hydrogencarbonate; 1-butyl-3-methylimidazolium Tetrafluoroborate at 55 - 65℃; for 24h; Title compound not separated from byproducts;

O-methylisourea hemisulfate (29427-58-5) + chloroformic acid ethyl ester (541-41-3) + methyl 2-(2-chlorophenylmethylene)acetoacetate (67593-46-8) → methyl 4-(2-chlorophenyl)-3-ethoxycarbonyl-6-methyl-2-oxo-3,4-dihydropyrimidine-1H-5-carboxylate

Conditions	Yield
Stage #1: O-methylisourea hemisulfate; methyl 2-(2-chlorophenylmethylene)acetoacetate With sodium hydrogencarbonate; 1-butyl-3-methylimidazolium Tetrafluoroborate at 55 - 65℃; for 24h; Stage #2: chloroformic acid ethyl ester With pyridine In ethanol at 20℃; for 0.5h; Stage #3: With hydrogenchloride In methanol at 20℃; for 0.666667h;

methyl 2-(2-chlorophenylmethylene)acetoacetate (67593-46-8) → 4-(2-Chloro-phenyl)-2,6-dimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-methyl ester 5-(2-oxo-propyl) ester (99880-13-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 47 percent / ethanol / Heating 2: 84 percent / MeSO3H, H2O / ethanol / 6 h / Heating View Scheme

methyl 2-(2-chlorophenylmethylene)acetoacetate (67593-46-8) → 3-Aza-1,5-dicarbomethoxy-9-(2-chlorophenyl)-3-methyl-2,4-dimethylenebicyclo<3.3.1>nonane (109346-07-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 5 percent / ethanol / Heating 2: Diisopropylamine, Butyllithium / 1) THF View Scheme

methyl 2-(2-chlorophenylmethylene)acetoacetate (67593-46-8) → 2-(2-azidoethoxy)methyl-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine (88150-46-3)

Conditions	Yield
With ammonium acetate In methanol; ethanol

3-Aminocrotononitrile (1118-61-2) + methyl 2-(2-chlorophenylmethylene)acetoacetate (67593-46-8) → methyl 4-(2-chlorophenyl)-5-cyano-1,4-dihydro-2,6-dimethylpyridine-3-carboxylate (67593-29-7)

Conditions	Yield
In ethanol Inert atmosphere; Reflux;

Upstream product

• 89-98-5 2-chloro-benzaldehyde 
• 105-45-3 acetoacetic acid methyl ester 

Downstream Products

• 88150-62-3 4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-2-[2-phthalimidoethoxymethyl]-1,4-dihydropyridine 
• 316828-72-5 4-(2-chloro-phenyl)-2,6-bis-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethoxymethyl]-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester 
• 88150-46-3 2-(2-azidoethoxy)methyl-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine 
• 84157-61-9 4-(2-Chloro-phenyl)-2-methyl-6-(2-morpholin-4-yl-ethoxymethyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 5-ethyl ester 3-methyl ester 
• 67593-29-7 methyl 4-(2-chlorophenyl)-5-cyano-1,4-dihydro-2,6-dimethylpyridine-3-carboxylate 
• 225939-13-9 4-(2-chlorophenyl)-2-(2,2-diethoxy-ethoxymethyl)-6-methyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester 
• 109346-07-8 3-Aza-1,5-dicarbomethoxy-9-(2-chlorophenyl)-3-methyl-2,4-dimethylenebicyclo<3.3.1>nonane 
• 99880-13-4 4-(2-Chloro-phenyl)-2,6-dimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-methyl ester 5-(2-oxo-propyl) ester 
• 109329-68-2 dimethyl 4-(2-chlorophenyl)-1,2,6-trimethyl-1,4-dihydropyridine-3,5-dicarboxylate 
• 109329-69-3 2-(2-Chloro-phenyl)-4-methyl-6-methylamino-cyclohexa-3,5-diene-1,3-dicarboxylic acid dimethyl ester 
• 103785-54-2 4-(2-Chloro-phenyl)-2,6-dimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-methyl ester 5-(2-methyl-[1,3]dioxolan-2-ylmethyl) ester 

Relevant academic research and scientific papers

Discovery of novel cyanodihydropyridines as potent mineralocorticoid receptor antagonists

A new 1,4-dihydropyridine 5a, containing a cyano group at the C3 position, was recently reported to possess excellent mineralocorticoid receptor (MR) antagonist in vitro potency and no calcium channel-blocker (CCB) activity. In the present study, we report the structure-activity relationships of this novel series of cyano ester dihydropyridines that resulted in R6 substituted analogues with improved metabolic stability while maintaining excellent MR antagonist activity and selectivity against other nuclear receptors. Further structure optimization with the introduction of five-membered ring heterocycles at R6 resulted in compounds with excellent MR antagonist potency and a suitable pharmacokinetic profile. In vivo studies of a promising tool compound in the Dahl salt-sensitive rat model of hypertension showed similar blood pressure (BP) reduction as the steroidal MR antagonist eplerenone, providing proof-of-concept (POC) for a nonsteroidal, orally efficacious MR antagonist.

Reaction of aromatic aldehydes with β-dicarbonyl compounds in a catalytic system: Piperidinium acetate - 1-butyl-3-methylimidazolium tetrafluoroborate ionic liquid

Condensation of aromatic (heteroaromatic) aldehydes with 1,3-dicarbonyl compounds under the 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim][BF4]) ionic liquid - piperidinium acetate catalytic system (0.2 equiv. of each component) in the absence of a solvent affords, depending on the structures of the reagents, 2-arylidene derivatives of methyl acetoacetate and acetylacetone, diethyl 2,4-bis(trifluoroacetyl)-3-phenylpentanedioate, or dimethyl 2-aryl-4-hydroxy-6-oxocyclohexane-1,3-dicarboxylates. The reactions of the resulting 2-arylidene derivatives with O-methylisourea in the [Bmim][BF 4] ionic liquid produced methyl 2-methoxy-4-methyl-6- aryldihydropyrimidine-5-carboxylates and 1-(2-methoxy-4-methyl-6- phenyldihydropyrimidin-5-yl)ethanone (mixtures of 3,6- and 1,6-dihydro isomers), which were transformed into the corresponding 3,4-dihydropyrimidin-2(1H)-one derivatives.

Process for the preparation of 1,4-dihydropyridinedicarboxylic esters

Benzylidene intermediates, useful in the preparation of dihydropyridines such as nifedipine and amlodipine, are formed by reaction of a ketocarboxylic adid ester with an aldehyde in the presence of a catalytic amount of dimethylamine acetate.