4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitro- CAS 162012-67-1
4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitro- Basic information
| Product Name: | 4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitro- |
| Synonyms: | 4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitro-;N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine;4-(3-chloro-4-fiuoro-phen...;4-(3-chloro-4-fiuoro-phenylaMino)-7-fluoro-6-nitroquninazoline;N-(3-chloro-4-fluorophenyl)-N-(7-fluoro-6-nitroquinazolin-4-yl)acetaMide;(3-Chloro-4-fluorophenyl)(7-fluoro-6-nitroquinazolin-4-yl)amine;N-(3-Chloro-4-fluorophenyl)-7-fluoro-6-nitro-4-quinazolinamine;Afatinib intermediate A |
| CAS: | 162012-67-1 |
| MF: | C14H7ClF2N4O2 |
| MW: | 336.68 |
| EINECS: | 000-000-0 |
| Product Categories: | API intermediates;162012-67-1 |
| Mol File: | 162012-67-1.mol |
4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitro- Chemical Properties
| Melting point | 242-244℃ |
| Boiling point | 489℃ |
| density | 1.616 |
| Fp | 249℃ |
| storage temp. | 2-8°C(protect from light) |
| solubility | DMSO (Slightly), Methanol (Slightly, Sonicated) |
| pka | 5.07±0.70(Predicted) |
| form | Solid |
| color | Yellow to Dark Yellow |
Safety Information
| HS Code | 2933.59.8000 |
| 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 | 162012-69-3 367-21-5 162012-67-1 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- Preparation Products And Raw materials
| Raw materials | 7-Fluoro-6-nitro-4-hydroxyquinazoline-->3-Chloro-4-fluoroaniline-->4-CHLORO-7-FLUORO-6-NITRO-QUINAZOLINE |
| Preparation Products | N-(3-chloro-4-fluorophenyl)-7-Methoxy-6-aminoquinazolin-4-aMine |
