205259-41-2

Basic information

• Product Name: Benzyl 2-amino-4-(benzyloxy)-5-methoxybenzoate
• Synonyms: Benzoic acid, 2-amino-5-methoxy-4-(phenylmethoxy)-, phenylmethyl ester;Benzyl 2-amino-4-(benzyloxy)-5-methoxybenzoate
• CAS NO: 205259-41-2
• Molecular Formula: C₂₂H₂₁NO₄
• Molecular Weight: 363.411
• Mol File: 205259-41-2.mol

Chemical Properties

• Boiling Point: 544.679 °C at 760 mmHg
• Flash Point: 216.221 °C
• Appearance: /
• Density: 1.215
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.617
• PKA: 2?+-.0.10(Predicted)
• CAS DataBase Reference: Benzyl 2-amino-4-(benzyloxy)-5-methoxybenzoate(CAS DataBase Reference)
• NIST Chemistry Reference: Benzyl 2-amino-4-(benzyloxy)-5-methoxybenzoate(205259-41-2)
• EPA Substance Registry System: Benzyl 2-amino-4-(benzyloxy)-5-methoxybenzoate(205259-41-2)

Safety Data

• Hazardous Substances Data: 205259-41-2(Hazardous Substances Data)

Usage

Uses

Used in Organic Synthesis:
Benzyl 2-amino-4-(benzyloxy)-5-methoxybenzoate is used as a building block in organic synthesis for the creation of various pharmaceuticals and bioactive molecules, leveraging its unique chemical structure to form complex organic compounds.
Used in Medicinal Chemistry:
In the field of medicinal chemistry, Benzyl 2-amino-4-(benzyloxy)-5-methoxybenzoate is utilized as a key intermediate in the synthesis of new drug candidates, potentially contributing to the development of novel therapeutic agents.
Used in Drug Development:
Benzyl 2-amino-4-(benzyloxy)-5-methoxybenzoate may have potential applications in the development of new drug candidates due to its chemical properties, although further research is necessary to fully explore its biological activity and potential uses in this area.

InChI:InChI=1/C22H21NO4/c1-25-20-12-18(22(24)27-15-17-10-6-3-7-11-17)19(23)13-21(20)26-14-16-8-4-2-5-9-16/h2-13H,14-15,23H2,1H3

Upstream product

• 100-39-0 benzyl bromide 
• 121-34-6 3-methoxy-4-hydroxybenzoic acid 
• 91203-74-6 4-benzyloxy-3-methoxybenzoic acid benzyl ester 
• 205259-40-1 4-benzyloxy-5-methoxy-2-nitrobenzoic acid benzyl ester 

Downstream Products

• 179688-01-8 7-(benzyloxy)-6-methoxyquinazolin-4(3H)-one 
• 387867-13-2 Tandutinib 
• 401903-53-5 4-[6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinazolin-4-yl]-piperazine-1-carboxylic acid (4-isopropoxy-phenyl)-amide 

Relevant articles and documents

Fluorine-containing 6,7-dialkoxybiaryl-based inhibitors for phosphodiesterase 10 A: Synthesis and in vitro evaluation of inhibitory potency, selectivity, and metabolism

Based on the potent phosphodiesterase 10 A (PDE10A) inhibitor PQ-10, we synthesized 32 derivatives to determine relationships between their molecular structure and binding properties. Their roles as potential positron emission tomography (PET) ligands were evaluated, as well as their inhibitory potency toward PDE10A and other PDEs, and their metabolic stability was determined in vitro. According to our findings, halo-alkyl substituents at position 2 of the quinazoline moiety and/or halo-alkyloxy substituents at positions 6 or 7 affect not only the compounds′ affinity, but also their selectivity toward PDE10A. As a result of substituting the methoxy group for a monofluoroethoxy or difluoroethoxy group at position 6 of the quinazoline ring, the selectivity for PDE10A over PDE3A increased. The same result was obtained by 6,7-difluoride substitution on the quinoxaline moiety. Finally, fluorinated compounds (R)-7-(fluoromethoxy)-6-methoxy-4-(3-(quinoxaline-2-yloxy)pyrrolidine-1-yl) quinazoline (16 a), 19 a-d, (R)-tert-butyl-3-(6-fluoroquinoxalin-2-yloxy) pyrrolidine-1-carboxylate (29), and 35 (IC50 PDE10A 11-65 nM) showed the highest inhibitory potential. Further, fluoroethoxy substitution at position 7 of the quinazoline ring improved metabolic stability over that of the lead structure PQ-10. Fluor your health: Phosphodiesterase 10 A (PDE10A) has emerged as an attractive target for the development of 18F-labelled brain imaging agents for positron emission tomography. A series of fluorinated dialkoxybiaryl compounds were synthesized and evaluated as PDE10A inhibitors, assisted by QSAR docking studies. The 7-fluoromethoxy derivative appears to be a promising candidate for further development.

SUBSTITUTED QUINAZOLINE INHIBITORS OF GROWTH FACTOR RECEPTOR TYROSINE KINASES

The present invention relates to new substituted quinazoline inhibitors of vascular endothelial growth factor receptor tyrosine kinase, epidermal growth factor receptor tyrosine kinase, and/or REarranged during Transfection tyrosine kinase, pharmaceutical compositions thereof, and methods of use thereof.

CHEMICAL PROCESS

The present invention relates to chemical processes for the manufacture of certain quinazoline derivatives, or pharmaceutically acceptable salts thereof. The invention also relates to processes for the manufacture of certain intermediates useful in the manufacture of the quinazoline derivatives and to processes for the manufacture of the quinazoline derivatives utilising said intermediates. In particular, the present invention relates to chemical processes and intermediates useful in the manufacture of the compound 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline.

CHEMICAL PROCESS

The present invention relates to chemical processes for the manufacture of certain quinazoline derivatives, or pharmaceutically acceptable salts thereof. The invention also relates to processes for the manufacture of certain intermediates useful in the manufacture of the quinazoline derivatives and to processes for the manufacture of the quinazoline derivatives utilising said intermediates. In particular, the present invention relates to chemical processes and intermediates useful in the manufacture of the compound 4-(4- bromo-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline.

Potent and Selective Inhibitors of Platelet-Derived Growth Factor Receptor Phosphorylation. 3. Replacement of Quinazoline Moiety and Improvement of Metabolic Polymorphism of 4-[4-(N-Substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline Derivatives

We have previously reported that a series of 4-[4-(N-substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline derivatives were potent and selective inhibitors of platelet-derived growth factor receptor (PDGFR) phosphorylation and demonstrated several biological effects such as suppression of neointima formation following balloon injury in rat carotid artery by oral administration. Here, we investigated structure-activity relationships of the 6,7-dimethoxyquinazolinyl moiety. In regard to 6,7-dimethoxy groups, ethoxy analogues showed potent activity (IC50 of 16b is 0.04 μM; IC50 of 17a is 0.01 μM) and further extension of the alkyl group reduced activity. Interestingly, methoxyethoxy (IC50 of 16j is 0.02μM; IC50 of 17h is 0.01 μM) and ethoxyethoxy (IC50 of 17j is 0.02 μM) analogues showed the most potent activity, suggesting that the inserted oxygen atom significantly interacts with β-PDGFR. Among tricyclic quinazoline derivatives, the 2-oxoimidazo[4,5-e]quinazoline derivative 21a showed potent activity (IC 50 = 0.10 μM). Regarding replacements of quinazoline by other heterocyclic rings, pyrazolo[3,4-d]pyrimidine (39a, IC50 = 0.17 μM) and quinoline (IC50 of 40a is 0.18 μM; IC50 of 40b is 0.09 μM) derivatives showed potent activity. Isoquinoline and some pyridopyrimidine derivatives were completely inactive; therefore, 1-aza has an important role. Also 7-aza and 8-aza substitution on the parent quinazoline ring has a detrimental effect on the interaction with β-PDGFR. We also demonstrated that the substituents on the quinazoline ring possess major consequences for metabolic polymorphism. Although there existed extensive metabolizers and poor metabolizers in Sprague-Dawley rats administrated 6,7-dimethoxyquinazoline derivatives (1b and 1c), 6-(2-methoxy)ethoxy-7-methoxyquinazoline analogue 16k showed no metabolic polymorphism.

Identification of orally active, potent, and selective 4-piperazinylquinazolines as antagonists of the platelet-derived growth factor receptor tyrosine kinase family

We have previously found that the 4-[4-(N-substituted carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazolines can function as potent and selective inhibitors of platelet-derived growth factor receptor (PDGFR) phosphorylation. A series of highly potent, specific, orally active, small molecule kinase inhibitors directed against members of PDGFR receptor have been developed through modifications of the novel quinazoline template I. Systematic modifications in the A-bicyclic ring and D-rings of protype I were carried out to afford potent analogues, which display IC50 values of 50 values of 50-200 nM, whereas 15-20-fold less potent activity against CSF1R was observed. This analogue also inhibits autophosphorylation of Flt-3 ligand-stimulated wild-type Flt-3 and a constitutively activated Flt-3/internal tandem duplication (ITD) with IC50 values of 30-100 nM. Through this optimization process, 75 was found to be metabolically stable and has desirable pharmacokinetic properties in all animal species studied (F% > 50%, T1/2 > 8 h). Oral administration of 75 promotes mice survival and significantly delayed disease progression in a Flt-3/ITD-mediated leukemia mouse model and shows efficacy in a nude mouse model of chronic myelomonocytic leukemia.