Water → 2-Chloro-5-(6,7-dimethoxyquinazolin-4-yloxy)aniline

HRID 871671

Reaction equation

HRID 871671 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[CH:6][C:7]=1[Cl:8].[C:10](=[O:13])([O-])[O-].[Cs+].[Cs+].Cl[C:17]1[N:26]=[CH:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:18]=1.O.CN([CH:31]=[O:32])C>>[Cl:8][C:7]1[CH:6]=[CH:5][C:4]([O:9][C:25]2[C:24]3[C:19](=[CH:20][C:21]([O:13][CH3:10])=[C:22]([O:32][CH3:31])[CH:23]=3)[N:18]=[CH:17][N:26]=2)=[CH:3][C:2]=1[NH2:1]

Participants

6

Reactant 5

HCID 962WaterHCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 740542-ChloroquinazolineHCID 50700783-Amino-4-chlorophenol

Product 1

HCID 668763862-Chloro-5-(6,7-dimethoxyquinazolin-4-yloxy)aniline

Procedure

A solution of 3-amino-4-chlorophenol (1.00 g, 7.0 mmol) and cesium carbonate (3.38 g, 10.4 mmol) in DMF (20 mL) were heated at 80 C for 1 hr. The chloroquinazoline (1.61 g, 7.2 mmol) was added and the mixture heated for an additional hour. The mixture was poured into water (300 mL) and extracted with EtOAc twice. The combined extracts were washed with brine, dried with magnesium sulfate, filtered and concentrated. The residue was purified using silica gel chromatography eluting with EtOAc/hexane (30-70%), the main peak collected and triturated with DCM to afford 2-chloro-5-(6,7-dimethoxyquinazolin-4-yloxy)aniline. 1H NMR (300 MHz, DMSO d6) δ 3.96 (s, 6H), 5.55 (s, 2H), 6.45 (t, 1H), 6.76 (d, 1H), 7.25 (d, 1H), 7.36 (s, 1H), 7.50 (s, 1H), 8.55 (s, 1H); LC-MS (ESI) m/z 332 (M+H)+

Workup

  1. temperaturethe mixture heated for an additional hour
  2. extractionextracted with EtOAc twice
  3. washThe combined extracts were washed with brine
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified
  8. washeluting with EtOAc/hexane (30-70%)
  9. customthe main peak collected
  10. customtriturated with DCM

Sources & evidence

ORD record
ord-f6f03001d97f4108ba6db1cc0b1e2793
Source dataset
uspto-grants-2015_03
Patent number
US08969587B2

Linked notes

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