4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitro- Chemical Properties

Melting point:

242-244℃

Boiling point:

489℃

Density 

1.616

Flash point:

249℃

storage temp. 

2-8°C(protect from light)

solubility 

DMSO (Slightly), Methanol (Slightly, Sonicated)

form 

Solid

pka

5.07±0.70(Predicted)

color 

Yellow to Dark Yellow

Safety Information

HS Code 

2933.59.8000

4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitro- Usage And Synthesis

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

4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitro-(162012-67-1)Related Product Information

• N-(3-chloro-4-fluorophenyl)-7-Methoxy-6-nitroquinazolin-4-aMine
• Aprepitant
• methyl(E)-4-(methylamino)but-2-enoate
• (2R,3S)-2-[(1R)-1-[3,5-Bis(trifluoroMethyl)phenyl]ethoxy]-3-(phenyl)Morpholine hydrochloride
• (2S,3R)-2-((S)-1-(3,5-bis(trifluoroMethyl)phenyl)ethoxy)-3-(4-fluorophenyl)Morpholine
• TRANS-4-AMINOCROTONIC ACID
• 7-Fluoro-4-quinazolone
• Afatinib impurity 45
• Benzyl dihydrogen phosphate
• (2R,3R)-2-[(1R)-1-[3,5-Bis(trifluoroMethyl)phenyl]ethoxy]-3-(4-fluorophenyl)Morpholine
• trans-4-Dimethylaminocrotonic acid hydrochloride
• (S)-N4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)quinazoline-4,6-diaMine
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• (S)-(+)-3-Hydroxytetrahydrofuran
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