94-05-3

Usage

Uses

Used in Pharmaceutical Industry:
Ethyl (ethoxymethylene)cyanoacetate is used as a synthetic intermediate for the development of anti-inflammatory agents with gastroprotective effects in rats. Its unique structure allows for the creation of compounds that can effectively reduce inflammation while also providing protection to the gastrointestinal tract, making it a valuable component in the formulation of medications for inflammatory conditions.

InChI:InChI=1/C8H11NO3/c1-3-11-6-7(5-9)8(10)12-4-2/h6H,3-4H2,1-2H3/b7-6+

Upstream product

• 122-51-0 orthoformic acid triethyl ester 
• 105-56-6 ethyl 2-cyanoacetate 
• 108-24-7 acetic anhydride 

Downstream Products

• 52793-44-9 1-Benzoyl-5-amino-4-carboethoxy pyrazole 
• 52793-45-0 ethyl 5-amino-1-(4-methylphenylsulfonyl)-1H-pyrazole-4-carboxylate 
• 57338-24-6 (E)-ethyl 2-cyano-3-((4-nitrophenyl)amino)acrylate 
• 492456-51-6 (E)-2-Cyano-3-(3-ethoxy-4-nitro-phenylamino)-acrylic acid ethyl ester 
• 476006-23-2 5-amino-1-(2-hydroxy-3-phenoxy-propyl)-1H-pyrazole-4-carboxylic acid ethyl ester 
• 383911-62-4 5-amino-1-(2-hydroxy-2-phenylethyl)-1H-pyrazole-4-carboxylic acid ethyl ester 
• 909513-02-6 (E)-2-Cyano-3-(3-ethoxy-phenylamino)-acrylic acid ethyl ester 
• 908147-24-0 5-amino-1-(4-methyl-6-phenyl-cyclohex-3-enecarbonyl)-1H-pyrazole-4-carboxylic acid ethyl ester 
• 908147-25-1 5-amino-1-[6-(4-fluoro-phenyl)-4-methyl-cyclohex-3-enecarbonyl]-1H-pyrazole-4-carboxylic acid ethyl ester 
• 908147-27-3 5-amino-1-[6-(4-bromo-phenyl)-4-methyl-cyclohex-3-enecarbonyl]-1H-pyrazole-4-carboxylic acid ethyl ester 
• 908147-26-2 5-amino-1-[6-(4-chloro-phenyl)-4-methyl-cyclohex-3-enecarbonyl]-1H-pyrazole-4-carboxylic acid ethyl ester 
• 908147-28-4 5-amino-1-[4-methyl-6-(4-nitro-phenyl)-cyclohex-3-enecarbonyl]-1H-pyrazole-4-carboxylic acid ethyl ester 

Relevant academic research and scientific papers

Efficient, Protecting Group Free Kilogram-Scale Synthesis of the JAK1 Inhibitor GDC-4379

The development of an improved kilogram-scale synthesis of the JAK1 inhibitorGDC-4379for the treatment of asthma is described. The new process is highlighted by a step-economical construction of a 3-substituted-4-aminopyrazole employing a telescoped oximation and hydrazine condensation of a 1,3-dielectrophile to generate nitrosopyrazole and a novel copper-catalyzed NaBH4reduction of the nitroso group. The endgame process features an amidation of aminopyrazole with acid chloride under Schotten-Baumann conditions to provide access to the penultimate intermediate. A selective N-1 alkylation of the pyrazole moiety was accomplished under phase-transfer conditions, which deliveredGDC-4379with a defined particle-size distribution suitable for micronization after recrystallization and wet milling.

Preparation method of ethoxymethylene ethyl cyanoacetate

The invention discloses a preparation method of ethoxymethylene ethyl cyanoacetate. The method comprises the following steps: 1) adding triethyl orthoformate, ethyl cyanoacetate and acetic acid into areaction kettle, heating to 120-125 DEG C, evaporating out ethanol at the temperature, controlling the distillation speed, and distilling for 1 hour to obtain 15-20 L of ethanol; 2) titrating aceticacid into the reaction kettle, and carrying out reflux distillation on ethanol until no ethanol is distilled; 3) carrying out reduced pressure distillation to collect triethyl orthoformate to obtain an ethoxymethylene ethyl cyanoacetate crude product; and 4) carrying out vacuum distillation on the crude product to obtain the ethoxymethylene cyanoethyl acetate. According to the invention, no solvent is used in the reaction process of preparing the target product, only a small amount of acetic acid is used as the catalyst, and the target product can be obtained with high yield; and the preparation method disclosed by the invention is short in period and relatively low in cost, and the recycled triethyl orthoformate can be used as a reactant to be reused.

ANDROGEN RECEPTOR ANTAGONISTS

Compounds that inhibit the androgen receptor, pharmaceutical compositions comprising one or more of the compounds, as well as methods of treating cancer using such compounds are described.

Pyrazolo[3,4-d]pyrimidine derivatives containing a Schiff base moiety as potential antiviral agents

A series of pyrazolo[3,4-d]pyrimidine derivatives containing a Schiff base moiety were synthesized, characterised, and evaluated for their activity against tobacco mosaic virus (TMV). Biological assays indicated that several of the derivatives exhibited significant activity against TMV. In particularly, compounds 5y and 5aa displayed excellent inactivating activity against TMV, with half maximal effective concentration (EC50) values of 70.3 and 53.65 μg/mL, respectively, which were much better than that of ribavirin (150.45 μg/mL), and 5aa was superior to ningnanmycin (EC50 = 55.35 μg/mL). Interactions of compounds 5y and 5aa with TMV coat protein (TMV-CP) were investigated using microscale thermophoresis and molecular docking. Compounds 5y and 5aa displayed strong binding capability to TMV-CP with dissociation constant (Kd) values of 22.6 and 9.8 μM, respectively. These findings indicate that pyrazolo[3,4-d]pyrimidine derivatives containing a Schiff base may be potential antiviral agents.

Synthesis and physicochemical properties of merocyanine dyes based on dihydropyridine and fragments of cyanoacetic acid derivatives

Merocyanine dyes of the dihydropyridine series were prepared from salts of a(y)-picolinium and cyanoacetic acid derivatives. Their spectral characteristics suggesting their structure in solution were studied. The change in the spectral properties depending on the substituents introduced into the structure of the substituents and solvents used (solvatochromism) was considered. The protonation of the dyes was studied, and its regioselectivity was established.

Synthesis and physicochemical properties of merocyanine dyes based on dihydropyridine and fragments of cyanoacetic acid derivatives

Merocyanine dyes of the dihydropyridine series were prepared from salts of α(γ)-picolinium and cyanoacetic acid derivatives. Their spectral characteristics suggesting their structure in solution were studied. The change in the spectral properties depending on the substituents introduced into the structure of the substituents and solvents used (solvatochromism) was considered. The protonation of the dyes was studied, and its regioselectivity was established.

Synthetic method of pesticide intermediate pyrazole-4-ethyl formate

The invention discloses a synthetic method of pesticide intermediate pyrazole-4-ethyl formate. The method comprises the following steps: 1) ethyl cyanoacetate and triethyl orthoformate are placed in a flask, acetic anhydride is added for a reaction, an oil pump is used for performing underpressure distillation to obtain efhylene efhoxymethylene cyanoncetata; 2) efhylene efhoxymethylene cyanoncetata is dissolved in ethanol, hydrazine hydrate is added drop by drop, a solvent is used for underpressure distillation to obtain 3-amino-pyrazoles-4-ethyl formate; and 3) adding pyrazoles-4-ethyl formate and glacial acetic acid are added in a reaction bottle, hydrochloric acid is added drop by drop, a sodium nitrite solution is added drop by drop, after the reaction, ethanol is added for backflow and vacuum concentration, dichloromethane and water are added for stirring and layering, and an organic layer is re-crystallized to obtain the finished product. By employing ester condensation, cyclization and deamination reactions, the preparation technology is simple, and the product is easily purified, production cost is low, and the method is suitable for large-scale industrial production.

MULTISUBSTITUTED AROMATIC COMPOUNDS AS INHIBITORS OF THROMBIN

There are provided inter alia multisubstituted aromatic compounds useful for the inhibition of thrombin, which compounds include substituted pyrazolyl or substituted triazolyl. There are additionally provided pharmaceutical compositions. There are additionally provided methods of treating and preventing a disease or disorder, which disease or disorder is amenable to treatment or prevention by the inhibition of thrombin.

Substituted heteroaryl compounds and compositions and uses thereof

The invention discloses a substituted ceteroary compound as well as a composition and an application thereof. The compound is a compound shown in a formula (I) or a stereisomer, a tautomer, a nitric oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or prodrug of the compound shown in the formula (I). The invention further discloses a pharmaceutical composition including the compound. The compound and the pharmaceutical composition are capable of adjusting the activity of the AK kinase and can be used for preventing, processing, treating and relieving the JAK-mediated disease or disorder.

4-Substituted-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine derivatives: Design, synthesis, antitumor and EGFR tyrosine kinase inhibitory activity

Four series of some 4-substituted-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine derivatives 5a-f, 6a-f, 8a-f, and 9a-f were designed to be screened for their antitumor activity. All compounds were evaluated against breast (MCF-7) and lung (A-549) cell lines. Six compounds 5a, 5b, 6b, 6e, 9e, and 9f displaying activity against both cell lines were further estimated for their EGFR-TK inhibitory activity where they revealed 41-91% inhibition and compound 6b elicited the highest activity (91%). A docking study of these compounds into the ATP-binding site of EGFR-TK demonstrated their binding mode where H-bonding interaction with Met793 through N1 of pyrimidine or N2 of pyrazole was observed. Four series of compounds comprising the pyrazolo[3,4-d]pyrimidine core substituted at position 4 with various heterocyclic substitutions were synthesized. Antitumor activity and EGFR-TK inhibition were evaluated.