Hydrochloric Acid → 6-Amino-4-[3-chloro-4-(2-pyridylmethoxy)anilino]quinazoline

HRID 1397060Notes

Reaction equation

HRID 1397060 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[C:24]([N+:27]([O-])=O)[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.Cl>C(O)C.O.[Fe]>[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[C:24]([NH2:27])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 18967699N-[3-chloro-4-(2-pyridylmethoxy)phenyl]-6-nitro-quinazolin-4-amine

Product 1

HCID 189676876-Amino-4-[3-chloro-4-(2-pyridylmethoxy)anilino]quinazolineYield 54.1%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

N-[3-Chloro-4-(2-pyridylmethoxy)phenyl]-6-nitro-quinazolin-4-amine 4d (4.07 g, 10 mmol) and concentrated hydrochloric acid (2 mL, 24 mmol) were dissolved in 130 mL of the solvent mixture of 95% ethanol and water (V/V=10/3), followed by addition of iron powder (11.17 g, 200 mmol). The reaction mixture was heated to reflux for 2 hours, filtered while hot and the filtrate was concentrated under reduced pressure to remove ethanol. The resulting residue was adjusted to pH>7 with ammonium hydroxide, filtered and the filter cake was dried under vacuum, purified by silica gel column chromatography with elution system A to obtain the title compound N4-[3-chloro-4-(2-pyridylmethoxy)phenyl]quinazoline-4,6-diamine 4e (2.04 g, yield 54.1%) as a white solid.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 2 hours
  3. filtrationfiltered while hot and the filtrate
  4. concentrationwas concentrated under reduced pressure
  5. customto remove ethanol
  6. filtrationfiltered
  7. customthe filter cake was dried under vacuum
  8. custompurified by silica gel column chromatography with elution system

Sources & evidence

ORD record
ord-26a4e6101bc5440489256698ee0becf9
Source dataset
uspto-grants-2014_12
Patent number
US08901140B2

Reaction notes

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