N-(3-chloro-4-fluoro-phenyl)-7-(2-methoxyethoxy)-6-nitro-quinazolin-4-amine → N4-(3-Chloro-4-fluorophenyl)-7-(2-methoxyethoxy)quinazoline-4,6-diamine

HRID 2199351Notes

Reaction equation

HRID 2199351 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][O:26][CH3:27])=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]>C(O)(=O)C.[Fe]>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH2:24][CH2:25][O:26][CH3:27])=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

4

Reactant 1

HCID 18765556N-(3-chloro-4-fluoro-phenyl)-7-(2-methoxyethoxy)-6-nitro-quinazolin-4-amine

Product 1

HCID 18765584N4-(3-Chloro-4-fluorophenyl)-7-(2-methoxyethoxy)quinazoline-4,6-diamineYield 55.2%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Procedure

N-(3-Chloro-4-fluoro-phenyl)-7-(2-methoxyethoxy)-6-nitro-quinazolin-4-amine 8b (392 mg, 1 mmol) and iron powder (392 mg, 7 mmol) were dissolved in 20 mL of acetic acid. The reaction mixture was heated to reflux for 4 hours, concentrated under reduced pressure. The residue was added with 100 mL of saturated sodium bicarbonate, extracted with dichloromethane (100 mL×3). The combined organic extracts were washed with saturated brine (50 mL×2), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain the title compound N4-(3-chloro-4-fluoro-phenyl)-7-(2-methoxyethoxy)quinazoline-4,6-diamine 8c (200 mg, yield 55.2%) as a light yellow solid.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 4 hours
  3. concentrationconcentrated under reduced pressure
  4. additionThe residue was added with 100 mL of saturated sodium bicarbonate
  5. extractionextracted with dichloromethane (100 mL×3)
  6. washThe combined organic extracts were washed with saturated brine (50 mL×2)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-7fef96e5f1ca4f5a82d02757923be6a7
Source dataset
uspto-grants-2016_06
Patent number
US09358227B2

Reaction notes

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