4442-53-9

Usage

Chemical Properties

white to light yellow crystal powder

InChI:InChI=1/C9H8O4/c10-9(11)6-2-1-3-7-8(6)13-5-4-12-7/h1-3H,4-5H2,(H,10,11)

Synthetic route

2,3-dihydro-benzo[1,4]dioxine-5-carboxylic acid methyl ester → 2,3-dihydro-1,4-benzodioxine-5-carboxylic acid (4442-53-9)

Conditions	Yield
Stage #1: 2,3-dihydro-benzo[1,4]dioxine-5-carboxylic acid methyl ester With sodium hydroxide In water for 3h; Reflux; Stage #2: With hydrogenchloride In water	97%
With sodium hydroxide for 2h; Reflux;	95%
With methanol; sodium hydroxide In tetrahydrofuran; water at 75℃; for 2h;
With lithium hydroxide In water at 20℃;

2,3-dihydro-benzo[1,4]dioxine-5-carboxylic acid methyl ester → 2,3-dihydro-1,4-benzodioxine-5-carboxylic acid (4442-53-9) + methyl 6,7-dibromo-2,3-dihydrobenzo[b][1,4]dioxine-5-carboxylate

Conditions	Yield
With bromine; acetic acid at 60 - 70℃; for 18h;	A 30% B 32.6%

2,3-Dihydroxybenzoic acid (303-38-8) + ethylene dibromide (106-93-4) → 2,3-dihydro-1,4-benzodioxine-5-carboxylic acid (4442-53-9)

Conditions	Yield
With potassium hydroxide unter Ausschluss von Sauerstoff;
With potassium carbonate In N,N-dimethyl-formamide

methyl-2,3-dihydroxybenzoate (2411-83-8) → 2,3-dihydro-1,4-benzodioxine-5-carboxylic acid (4442-53-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 5 h / Reflux 2: sodium hydroxide / water / 3 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / acetone / 70 °C / Inert atmosphere 2: methanol; sodium hydroxide / water; tetrahydrofuran / 2 h / 75 °C View Scheme
Multi-step reaction with 2 steps 1.1: caesium carbonate / N,N-dimethyl-formamide / 0.5 h / 20 °C 1.2: 4 h / 80 °C 2.1: sodium hydroxide / 2 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 12 h / Reflux 2: lithium hydroxide / water / 20 °C View Scheme

2,3-Dihydroxybenzoic acid (303-38-8) → 2,3-dihydro-1,4-benzodioxine-5-carboxylic acid (4442-53-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: sulfuric acid / 10 h / Reflux 2: potassium carbonate / N,N-dimethyl-formamide / 5 h / Reflux 3: sodium hydroxide / water / 3 h / Reflux View Scheme
Multi-step reaction with 3 steps 1: sulfuric acid / 8 h / 90 °C 2: potassium carbonate / acetone / 70 °C / Inert atmosphere 3: methanol; sodium hydroxide / water; tetrahydrofuran / 2 h / 75 °C View Scheme
Multi-step reaction with 3 steps 1.1: sulfuric acid / 8 h / Reflux 2.1: caesium carbonate / N,N-dimethyl-formamide / 0.5 h / 20 °C 2.2: 4 h / 80 °C 3.1: sodium hydroxide / 2 h / Reflux View Scheme
Multi-step reaction with 3 steps 1: sulfuric acid / 12 h / 5 °C / Reflux 2: potassium carbonate / N,N-dimethyl-formamide / 12 h / Reflux 3: lithium hydroxide / water / 20 °C View Scheme

Upstream product

• 493-09-4 benzo-1,4-dioxane 
• 124-38-9 carbon dioxide 
• 214894-91-4 2,3-dihydro-benzo[1,4]dioxine-5-carboxylic acid methyl ester 
• 29668-43-7 2,3-dihydro-benzo[1,4]dioxine-5-carbaldehyde 
• 24677-78-9 2,3-dihydroxybenzaldehyde 
• 303-38-8 2,3-Dihydroxybenzoic acid 
• 2411-83-8 methyl-2,3-dihydroxybenzoate 
• 106-93-4 ethylene dibromide 

Downstream Products

• 38871-41-9 2,3-dihydrobenzo-[b]-1,4-dioxine-5-carbonyl chloride 
• 148703-14-4 2,3-dihydro-benzo[1,4]dioxin-5-carbonitrile 
• 349550-81-8 2,3-dihydrobenzo[b][1,4]dioxine-5-carboxamide 
• 66410-36-4 7-(chlorosulfonyl)-2,3-dihydrobenzo[b][1,4]dioxine-5-carboxylic acid 
• 66411-17-4 6,7-dibromo-2,3-dihydrobenzo[b][1,4]dioxine-5-carboxylic acid 
• 857650-87-4 N-[[1-(benzyl)-4-piperidinyl]methyl]-1,4-benzodioxane-5-carboxamide 
• 1186388-69-1 C₂₀H₁₉N₃O₃S 
• 532391-79-0 C₂₂H₂₆N₂O₄ 
• 16081-45-1 1,4-benzodioxan-5-amine 
• 98224-03-4 eltoprazine 
• 1400250-82-9 C₂₃H₁₇BrN₄O₃ 
• 66411-18-5 6,7-dibromo-8-nitro-2,3-dihydrobenzo[b][1,4]dioxine-5-carboxylic acid 
• 66411-22-1 8-amino-2,3-dihydrobenzo[b][1,4]dioxine-5-carboxylic acid 
• 158504-37-1 methyl 8-amino-2,3-dihydrobenzo[b][1,4]dioxine-5-carboxylate 

Relevant academic research and scientific papers

Synthesis of 2,3-dihydrobenzo[b][1,4]dioxine-5-carboxamide and 3-oxo-3,4-dihydrobenzo[b][1,4]oxazine-8-carboxamide derivatives as PARP1 inhibitors

Poly(ADP-ribose) polymerase 1 (PARP1), a widely explored anticancer drug target, plays an important role in single-strand DNA break repair processes. High-throughput virtual screening (HTVS) of a Maybridge small molecule library using the PARP1-benzimidazole-4-carboxamide co-crystal structure and pharmacophore model led to the identification of eleven compounds. These compounds were evaluated using recombinant PARP1 enzyme assay that resulted in the acquisition of three PARP1 inhibitors: 3 (IC50 = 12 μM), 4 (IC50 = 5.8 μM), and 10 (IC50 = 0.88 μM). Compound 4 (2,3-dihydro-1,4-benzodioxine-5-carboxamide) was selected as a lead and was subjected to further chemical modifications, involving analogue synthesis and scaffold hopping. These efforts led to the identification of (Z)-2-(4-hydroxybenzylidene)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-8-carboxamide (49, IC50 = 0.082 μM) as the most potent inhibitor of PARP1 from the series.

Quinazoline heterocyclic compounds as well as preparation method and application thereof

The invention provides quinazoline heterocyclic compounds as well as a preparation method and an application thereof and belongs to the field of medicinal chemistry. The structural formula is shown as a formula (I) in the specification, wherein R represents -H and -CH3; R is defined in the specification, 8,10-dichloro-2,3-dihydro-[1,4] dioxane [2,3-f] quinazoline (IX) is prepared firstly, and then R and R substitution are performed. The compounds can be applied as PI3K (phosphoinositide 3-kinase) inhibitors for treating cancer.

Discovery of 2-((2-chloro-6-fluorophenyl)amino)-N-(3-fluoro-5-(trifluoromethyl)phenyl)-1-methyl-7,8-dihydro-1H-[1,4]dioxino[2′,3′:3,4]benzo[1,2-d]imidazole-5-carboxamide as potent, selective and efficacious microsomal prostaglandin E2synthase-1

The discovery and SAR of potent, selective dioxane-fused tricyclic benz[d]imidazole derivatives as mPGES-1 inhibitor are herein described. Various amide modifications in this series afforded many potent mPGES-1 inhibitors, of which 17d proved to be suitab

Direct carboxylation of simple arenes with CO2 through a rhodium-catalyzed C-H bond activation

Direct carboxylation of simple arenes under atmospheric pressure of CO2 is achieved through a rhodium-catalyzed C-H bond activation without the assistance of a directing group. Various arenes such as benzene, toluene, xylene, electron-rich or electron-deficient benzene derivatives, and heteroaromatics are directly carboxylated with high TONs. This journal is

Synthesis, biological evaluation, and molecular docking studies of novel 2-styryl-5-nitroimidazole derivatives containing 1,4-benzodioxan moiety as FAK inhibitors with anticancer activity

A series of 2-styryl-5-nitroimidazole derivatives containing 1,4-benzodioxan moiety (3a-3r) has been designed, synthesized and their biological activities were also evaluated as potential antiproliferation and focal adhesion kinase (FAK) inhibitors. Among all the compounds, 3p showed the most potent activity in vitro which inhibited the growth of A549 with IC 50 value of 3.11 μM and Hela with IC50 value of 2.54 μM respectively. Compound 3p also exhibited significant FAK inhibitory activity (IC50 = 0.45 μM). Docking simulation was performed for compound 3p into the FAK structure active site to determine the probable binding model.

TRICYCLIC COMPOUNDS AS mPGES-1 INHIBITORS

The present disclosure is directed to compounds of formula (I), and pharmaceutically acceptable salts thereof, as m PGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (m PGES-1) enzyme and are therefore useful in the treatment of pain and/or inflammation from a variety of diseases or conditions, such as asthma, osteoarthritis, rheumatoid arthritis, acute or chronic pain and neurodegenerative diseases.

Synthesis, crystal structures, insecticidal activities, and structure-activity relationships of novel N ′- Tert -Butyl- N ′-substituted-benzoyl- N -[di(octa)hydro]benzofuran{(2,3-dihydro)benzo[1, 3]([1,4])dioxine}carbohydrazide derivatives

Several series of novel N′-tert-butyl-N′-substituted-benzoyl-N- [di(octa)hydro]benzofuran{(2,3-dihydro)benzo[1,3]([1,4])dioxine}carbohydrazide derivatives Ia, Ib, IIa-IIg, IIIa, IIIb, and Va-Vc were designed and synthesized. Their structures were confirmed by 1H NMR spectra, HRMS, and X-ray single-crystal structures. The larvicidal activities against oriental armyworm, beet armyworm, diamond-back moth, and corn borer of these compounds were evaluated and contrasted with those of RH-2485, JS-118, and ANS-118. The larvicidal activities against oriental armyworm indicate that monosubstituent or multisubstituents and the substituting group position cannot promote increasing activities and that the cycle region in the general structure of IIa-IIg is much more sensitive to activity than that in the general structure of Ia and Ib. The space volume of the A ring in the structure of Va cannot be too large; if it is, the activity will be decreased significantly. Stomach toxicities against beet armyworm, diamond-back moth, and corn borer of compounds Ia, Ib and IIg indicate that benzoheterocyclic analogues of N-tert-butyl-N,N′- diacylhydrazines show significant selectivities to different lepidopterous pests.

Piperazine derivatives as therapeutic agents

Substituted piperazine compounds of formula I STR1 in which HET is a substituted pyrazole, imidazole or 1,2,4-triazole have utility in the treatment of central nervous system disorders, for example depression, anxiety, psychoses (for example schizophrenia), tardive dyskinesia, Parkinson's disease, obesity, hypertension, Tourette's syndrome, sexual dysfunction, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, senile dementia, obsessive-compulsive behaviour, panic attacks, social phobias, eating disorders and anorexia, cardiovascular and cerebrovascular disorders, non-insulin dependent diabetes mellitus, hyperglycaemia, constipation, arrhythmia, disorders of the neuroendocrine system, stress, prostatic hypertrophy, and spasticity.

Heterocyclic compounds

The invention relates to compound of general formula (I): STR1 wherein: Z represents O or CH 2n is from 0 to 4R, X and Y are as defined in the description, andA represents STR2 wherein R 1, R 2, R 6, R 7 and T'' are as defined in the description,and medicinal products containing the same are useful in treating or in preventing melatoninergic disorders.