81918-01-6

Basic information

• Product Name: Diethyl 2-[4-(chlorobenzoyl)amino]Malonate
• Synonyms: Diethyl 2-[4-(chlorobenzoyl)amino]Malonate;DIETHYL 4-CHLOROBENZAMIDOMALONATE[REBAMIPIDE INTERMEDIATE];[(4-Chlorobenzoyl)-amino]-propanedioic acid diethyl ester;Diethyl 2-(4-chlorobenzaMido)Malonate;diethyl [(4-chlorobenzoyl)amino]propanedioate;diethyl 2-[(4-chlorobenzoyl)amino]propanedioate
• CAS NO: 81918-01-6
• Molecular Formula: C₁₄H₁₆ClNO₅
• Molecular Weight: 313.73354
• Product Categories: (intermediate of rebamipide)
• Mol File: 81918-01-6.mol

Chemical Properties

• Boiling Point: 458.625°C at 760 mmHg
• Flash Point: 231.168°C
• Appearance: /
• Density: 1.264g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.525
• Storage Temp.: 2-8°C
• PKA: 11.56±0.46(Predicted)
• CAS DataBase Reference: Diethyl 2-[4-(chlorobenzoyl)amino]Malonate(CAS DataBase Reference)
• NIST Chemistry Reference: Diethyl 2-[4-(chlorobenzoyl)amino]Malonate(81918-01-6)
• EPA Substance Registry System: Diethyl 2-[4-(chlorobenzoyl)amino]Malonate(81918-01-6)

Safety Data

• Hazardous Substances Data: 81918-01-6(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Synthesis:
Diethyl 2-[4-(chlorobenzoyl)amino]Malonate is used as a reagent for the synthesis of indole-based PPARγ ligands. PPARγ, or peroxisome proliferator-activated receptor gamma, is a nuclear receptor that plays a crucial role in the regulation of cellular differentiation, development, and the metabolism of glucose and lipids. Ligands for this receptor have potential applications in the treatment of type 2 diabetes, obesity, and other metabolic disorders.
In the synthesis of indole-based PPARγ ligands, Diethyl 2-[4-(chlorobenzoyl)amino]Malonate acts as a versatile building block that can be further modified and functionalized to create a variety of compounds with different biological activities. Its presence in the final product contributes to the overall efficacy and selectivity of the ligands towards the PPARγ receptor.
Used in Chemical Research:
Beyond its applications in pharmaceutical synthesis, Diethyl 2-[4-(chlorobenzoyl)amino]Malonate is also utilized in chemical research for the development of new synthetic methods and the exploration of novel chemical reactions. Its unique reactivity and structural features make it an interesting target for chemists looking to expand the scope of organic synthesis and discover new ways to construct complex molecules.

InChI:InChI=1/C14H16ClNO5/c1-3-20-13(18)11(14(19)21-4-2)16-12(17)9-5-7-10(15)8-6-9/h5-8,11H,3-4H2,1-2H3,(H,16,17)

Upstream product

• 13433-00-6 diethyl aminomalonate hydrochloride 
• 122-01-0 4-chloro-benzoyl chloride 
• 6829-40-9 aminomalonic acid diethyl ester 

Downstream Products

• 81918-03-8 2-(4-Chlorbenzoylamino)-2-brommalonsaeure-diethylester 
• 909699-85-0 2-(6-benzyloxy-1H-indol-3-ylmethyl)-2-(4-chloro-benzoylamino)-malonic acid diethyl ester 
• 81918-06-1 2-(4-Chloro-benzoylimino)-malonic acid diethyl ester 
• 81917-94-4 2-(4-Chloro-benzoylamino)-2-vinyl-malonic acid diethyl ester 
• 90098-04-7 rebamipide 
• 1028268-32-7 ethyl 2-(4-chlorobenzamido)-2-ethoxyoxo-3-[2-(1H)-quinolin-4-yl]propionate 
• 1379481-87-4 (E)-2-(p-chlorophenyl)-4,4-bis(ethoxycarbonyl)-5-dimethoxyphosphorylmethylidene-1,3-oxazoline 
• 1379481-82-9 (Z)-2-(p-chlorophenyl)-4,4-bis(ethoxycarbonyl)-5-dimethoxyphosphorylmethylidene-1,3-oxazoline 

Relevant articles and documents

Phenyl and Diaryl Ureas with Thiazolo[5,4-d]pyrimidine Scaffold as Angiogenesis Inhibitors: Design, Synthesis and Biological Evaluation

Angiogenesis is crucial for tumor growth and inhibition of angiogenesis has been regarded as a promising approach for cancer therapy. Vascular endothelial growth factor receptor-2 (VEGFR-2) is an important factor in angiogenesis. In this work, a novel series of thiazolo[5,4-d]pyrimidine derivatives inhibiting angiogenesis were rationally designed and synthesized. Their inhibitory activities against human umbilical vein endothelial cells (HUVEC) were investigated in vitro. 1-(4-Fluorophenyl)-3-{4-[(5-methyl-2-phenyl[1,3]thiazolo[5,4-d]pyrimidin-7-yl)amino]phenyl}urea (19b) and 1-(3-Fluorophenyl)-3-{4-[(5-methyl-2-phenyl[1,3]thiazolo[5,4-d]pyrimidin-7-yl)amino]phenyl}urea (19g) exhibited the most potent inhibitory effect on HUVEC proliferation (IC50=12.8 and 5.3 μm, respectively). Compound 19g could inhibit the migration of human umbilical vein endothelial cells. These results support the further investigation of these compounds as potent anticancer agents.

Process for synthesizing rebamipide

The invention provides a process for synthesizing rebamipide. The process comprises the following steps: taking aminomalonic acid diethyl ester and 4-chlorobenzoyl chloride as raw material substrates so as to prepare an intermediate 4-chlorobenzoyl diethyl aminomalonate; reacting with 4-bromomethylcarbostyril so as to obtain 2-(4-chlorobenzhylamino)-2-ethoxycarbonyl-3-[2(1H)-quinolinone-4-yl] ethyl propionate; and finally, heating and refluxing in a sodium alcoholate solution, concentrating, and re-crystallizing, thereby obtaining the final product. The rebamipide prepared by the process disclosed by the method is high in yield, and the purity can reach 99.2%.

Diarylureas and Diarylamides with Oxazolo[5,4-d]pyrimidine Scaffold as Angiogenesis Inhibitors

A series of oxazolopyrimidine-based ureas and amides were designed, synthesized, and biologically evaluated for their antiproliferative and antiangiogenic activities. These compounds were identified to exhibit inhibitory activities against human umbilical vein endothelial cells (HUVEC) in vitro. Among these compounds, compound 22 effectively inhibited the migration and capillary-like tube formation of human umbilical vein endothelial cells. It also exhibited a concentration-dependent inhibition on capillary sprouting from the rat aorta rings. Preliminary mechanistic studies revealed that compound 22 suppressed protein kinases activation, by decreasing PI3K and ERK 1/2 phosphorylation. These results support the further investigation of this class of compounds as potential anticancer agents.

Exploring the 7-oxo-thiazolo[5,4-d]pyrimidine core for the design of new human adenosine A3 receptor antagonists. Synthesis, molecular modeling studies and pharmacological evaluation

A new series of 5-methyl-thiazolo[5,4-d]pyrimidine-7-ones bearing different substituents at position 2 (aryl, heteroaryl and arylamino groups) was synthesized and evaluated in radioligand binding assays to determine their affinities at the human (h) A1, A2A, and A3 adenosine receptors (ARs). Efficacy at the hA2B and antagonism of selected ligands at the hA3 were also assessed through cAMP experiments. Some of the new derivatives exhibited good to high hA3AR affinity and selectivity versus all the other AR subtypes. Compound 2-(4-chlorophenyl)-5-methyl-thiazolo[5,4-d]pyrimidine-7-one 4 was found to be the most potent and selective ligand of the series (Ki hA3 Combining double low line 18 nM). Molecular docking studies of the reported derivatives were carried out to depict their hypothetical binding mode in our hA3 receptor model.

Process for preparing 2-(4-chlorobenzolamino)-3[ (1h)-quinolinon-4-yl] propionic acid

The invention relates to a novel method for preparing 2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl]propionic acid, also known as Rebamipide represented by the formula I and useful for treatment of peptic ulcer from alkyl 2-(4-chlorobenzoylamino)-2-alkoxycarbonyl-3-[2(1H)-quinolinon-4-yl]propionate represented by the formula II in the presence of a base solution for hydrolysis and decarboxylation to remove a carboxyl group.