| Identification | Back Directory | [Name]
4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitro- | [CAS]
162012-67-1 | [Synonyms]
)-7-fL
Afatinib/Dacomitinib
Afatinib Impurity 76
uoro-6-nitroquninazoL
Afatinib intermediate A
4-(3-chloro-4-fiuoro-phen...
N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitro-
N-(3-Cl-4-F-phenyl)-7-F-6-NO2-4-quinazolinamine
N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquninazoline
4-(3-Chloro-4-fluoroanilino)-7-fluoro-6-nitroquinazoline
3-Chloro-4-fluorophenyl)(7-fluoro-6-nitroquinazolin-4-yl)
4-Quizolimine, N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitro-
4-[(3-Chloro-4-fluorophenyl)amino]-7-fluoro-6-nitroquinazoline
N-(3-Chloro-4-fluorophenyl)-7-fluoro-6-nitro-4-quinazolinamine
N-(3-chloro-4-fluorophenyl)-7-fiuoro-6-nitro-4-quinazolinaMine
4-(3-chloro-4-fiuoro-phenylaMino)-7-fluoro-6-nitroquninazoline
N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine
(3-Chloro-4-fluorophenyl)(7-fluoro-6-nitroquinazolin-4-yl)amine
4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-fluoro-6-ni...
N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitro quinazoline-4-amine
4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitro-
N-(4-(3-chloro-4-fluorophenyl))-7-fluoro-6nitroquinazolin-4-amine
N - (3-chloro-4-fluorophenyl) -7-fluoro-6-nitro-4-quinazoline amine
4- quinazoline amine, N- (3-chloro-4-fluorophenyl) -7-fluoro-6-nitro -
N-(3-chloro-4-fluorophenyl)-N-(7-fluoro-6-nitroquinazolin-4-yl)acetaMide
4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitro- ISO 9001：2015 REACH
Afatinib int-1 N-(3-Chloro-4-fluorophenyl)-7-fluoro-6-nitro-4-quinazolinamine
N-(3-Chloro-4-fluorophenyl)-7-fluoro-6-nitro-4-quinazolinamine (3-Chloro-4-fluorophenyl)(7-fluoro-6-nitroquinazolin-4-yl)amine | [EINECS(EC#)]
-0 | [Molecular Formula]
C14H7ClF2N4O2 | [MDL Number]
MFCD09998825 | [MOL File]
162012-67-1.mol | [Molecular Weight]
336.69 |
| Chemical Properties | Back Directory | [Melting point ]
242-244℃ | [Boiling point ]
489℃ | [density ]
1.616 | [Fp ]
249℃ | [storage temp. ]
Keep in dark place,Sealed in dry,2-8°C | [solubility ]
DMSO (Slightly), Methanol (Slightly, Sonicated) | [form ]
Solid | [pka]
5.07±0.70(Predicted) | [color ]
Yellow to Dark Yellow |
| Hazard Information | Back Directory | [Uses]
4-(3-Chloro-4-fluorophenylamino)-7-fluoro-6-nitroquninazoline is an intermediate in the synthesis of Afatinib (A355300), an aminocrotonylamino-substituted quinazoline derivative used for treating cancer and diseases of the respiratory tract, lungs, gastrointestinal tract, bile duct, and gallbladder. | [Synthesis]
The general procedure for the synthesis of N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitro-4-quinazolinamine from 7-fluoro-6-nitro-4-hydroxyquinazoline and 3-chloro-4-fluoroaniline is as follows:
Method 1 (one-pot reaction):
1. 7-fluoro-6-nitro-4-hydroxyquinazoline (5 g, 23.9 mmol) was added to a 100 mL single neck flask.
2. Phosphoryl chloride (44.6 mL, 478 mmol) was added and heated to reflux at 150 °C for 5 hours.
3. Upon completion of the reaction, phosphorous trichloride was removed by evaporation.
4. The residue was diluted with anhydrous dichloromethane and evaporated again, and the process was repeated 3 times.
5. After dilution with acetonitrile (100 mL), 3-chloro-4-fluoroaniline (2.3 g, 15.8 mmol) was added. 6.
6. Heat to reflux overnight and a yellow solid precipitated during the reaction.
7. The yellow solid was filtered and dried to afford the target product N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitro-4-quinazolinamine (4.8 g, 56% yield).
Product characterization data:
1H-NMR (d-DMSO, 400 MHz, δppm): 10.61 (br, 1H), 9.68 (d, J=10.8 Hz, 1H), 8.81 (s, 1H), 8.10-8.13 (d, J=7.6 Hz, 1H), 8.05-8.07 (d, J=8 Hz, 1H), 7.81-7.85 (m. 1H), 7.50-7.54 (d, J=8Hz, 1H). | [References]
[1] Patent: EP3181553, 2017, A1. Location in patent: Paragraph 0123; 0124 |
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