314771-76-1

Basic information

• Product Name: (S)-N4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)quinazoline-4,6-diaMine
• Synonyms: 4-QuinazolinaMine, N-(3-chloro-4-fluorophenyl)-6-amine-7-[[(3S)-tetrahydro-3-furanyl]oxy]-;4,6-Quinazolinediamine, N4-(3-chloro-4-fluorophenyl)-7-[[(3S)-tetrahydro-3-furanyl]oxy]-;Afatinib-des(4-dimethylamino-2-en-1-oxo)butyl;Intermediates of sunitinib;(S)-N4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)quinazoline-4,6-diaMine;N4-(3-Chloro-4-fluorophenyl)-7-[[(3S)-tetrahydro-3-furanyl]oxy]-4,6-quinazolinediamine;7-((S)-tetrahydrofuran-3-yloxy)-4-(3-chloro-4-fluorophenyl) aMino-6-aMinoquinazoline;Afatinib IMpurity B
• CAS NO: 314771-76-1
• Molecular Formula: C18H16ClFN4O2
• Molecular Weight: 374.7966432
• EINECS: 1312995-182-4
• Product Categories: Afatinib Dimaleate
• Mol File: 314771-76-1.mol
• Article Data: 37

Chemical Properties

• Boiling Point: 559.0±50.0 °C(Predicted)
• Appearance: /
• Density: 1.473±0.06 g/cm3 (20 ºC 760 Torr)
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• PKA: 5.89±0.30(Predicted)
• CAS DataBase Reference: (S)-N4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)quinazoline-4,6-diaMine(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-N4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)quinazoline-4,6-diaMine(314771-76-1)
• EPA Substance Registry System: (S)-N4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)quinazoline-4,6-diaMine(314771-76-1)

Safety Data

• Hazardous Substances Data: 314771-76-1(Hazardous Substances Data)

Usage

Uses

(S)-N4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)quinazoline-4,6-diamine can be used as organic synthesis intermediate and pharmaceutical intermediate, mainly used in laboratory research and development process and chemical production process.

Synthesis

To a solution of 4-(3-chloro-4-fluorophenyl)amino-6-nitro-7-[[(S)-tetrahydro-3-furanyl]oxy]- quinazoline (1.34 g, 3.31 mmol) and ammonium chloride (496 mg, 9.27 mmol) in anhydrous DMF (22 mL), Raney nickel [1.5 mL, 50 % (w/v) in water] was added to the reaction mixture and stirred under an atmosphere of hydrogen at 40 °C for 2 h. After 2 h the reaction was diluted with EtOH (10 mL), filtered through diatomaceous earth and washed with a large excess of EtOH. The residue was concentrated under reduced pressure and purified by column chromatography eluting with CHCl3/MeOH (95:5) to give 6 as a viscous brown oil (950 mg, 77 %).

Upstream product

• 314771-88-5 4-[(3-chloro-4-fluorophenyl)amino]-6-nitro-7-[(S)-(tetrahydrofuran-3-yl)oxy]quinazoline 
• 367-21-5 3-chloro-4-fluorophenylamine 
• 162012-70-6 4-chloro-7-fluoro-6-nitroquinazoline 
• 162012-67-1 N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine 
• 31374-18-2 7-chloro-3,4-dihydroquinazolin-4-one 
• 53449-14-2 7-chloro-6-nitro-4(3H)-quinazolinone 
• 162012-71-7 4,7-dichloro-6-nitro-quinazoline 
• 179552-73-9 7-chloro-N-(3-chloro-4-fluorophenyl)-6-nitroquinazolin-4-amine 
• 945553-94-6 N-((3-chloro-4-fluorophenyl)-6-nitro-7-phenylsulfonyl)quinazolin-4-one 
• 446-32-2 4-fluoroanthranilic acid 
• 16499-57-3 7-fluoro-3,4-dihydroquinazolin-4-one 
• 162012-69-3 7-fluoro-6-nitro-4-hydroxyquinazoline 
• 162012-69-3 7-fluoro-6-nitro-3H-quinazolin-4-one 
• 16499-57-3 7-fluoro-3H-quinazolin-4-one 

Relevant articles and documents

Isolation and structural characterization of degradation products of afatinib dimaleate by LC-Q-TOF/MS/MS and NMR: cytotoxicity evaluation of afatinib and isolated degradation products

Afatinib is an irreversible tyrosine kinase receptor inhibitor which was approved lately by USFDA for the treatment of metastatic non-small cell lung cancer (NSCLC). AFT was subjected to stress degradation studies under hydrolytic (acid, base and neutral), oxidative, thermal and photolytic conditions to investigate the inherent stability of the drug. The present study describes the simple and rapid HPLC method development for the selective separation of the AFT and its degradation products. The drug and degradation products were separated on Agilent Eclipse plus C18 (150 × 4.6 mm, 5 μ) column with ammonium acetate buffer (10 mM, pH 6.7) in gradient elution mode. The drug was found to be unstable in all the conditions studied. The developed chromatographic method was extended to tandem mass spectrometry (QTOF-MS) for the characterization of the degradation products. A total of 11 unknown degradation products were characterized using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS/MS). Two major degradation products (DP2 and DP3) were isolated using preparative HPLC and their structures were confirmed by conducting 1H and 13C NMR experiments. The isolated DPs were evaluated for their anticancer potential using non small cell lung cancer cell line A549. The IC50 values for AFT, DP2 and DP3 were found to be 15.02 ± 1.49, 25.00 ± 1.26 and 32.56 ± 0.11 respectively. The in silico toxicity studies were performed employing ProTox-II software for the assessment of toxicity potential of drug and its degradation products. Finally, the developed chromatographic method was validated as per the International Conference on Harmonization guideline Q2 (R1).

Preparation method of afatinib intermediate

The invention discloses an afatinib intermediate preparation method, which comprises: (1) adding a compound represented by a formula II, sodium thiosulfate, sodium bicarbonate and N, N-dimethylformamide into a reaction device, heating, completely reacting

Preparation method and application of aniline quinazoline intermediate

The invention discloses a preparation method and application of an aniline quinazoline intermediate. The preparation method comprises the following steps: with N-(3-chloro-4-fluorophenyl)-7-[(S)-tetrahydro-3-furyl-oxy]-6-nitro-4-quinazolinamine as a raw m