2,4-Dichloro-6-methoxyquinazoline → 2-Chloro-6-methoxyquinazoline

HRID 2201501Notes

Reaction equation

HRID 2201501 reaction equation
[Cl:1][C:2]1[N:11]=[C:10](Cl)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:13][CH3:14])[CH:8]=2)[N:3]=1.N.O>C(Cl)Cl.[Cl-].[Na+].O.[Zn]>[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:13][CH3:14])[CH:8]=2)[N:3]=1

Participants

6

Reactant 2

HCID 99913972,4-Dichloro-6-methoxyquinazolineHCID 12896473Azane;hydrate

Product 1

HCID 592548522-Chloro-6-methoxyquinazolineYield 68.1%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 6344DichloromethaneSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 2,4-dichloro-6-methoxyquinazoline (400 mg, 1.75 mmol) in CH2Cl2 (10 mL) was added brine (10 mL) containing 9% NH3.H2O. Then zinc powder (336 mg, 5.25 mmol) was added and the mixture was refluxed for 2 hours. The mixture was diluted with CH2Cl2 (50 mL) and filtered off, the filtrate was neutralized by 2M HCl to pH 7. The aqueous layer extracted with CH2Cl2 (20 mL×2), the combined organic layer washed with brine (30 mL), dried over Na2SO4, filtered and concentrated to give the crude product, which was purified by silica gel column (PE/EtOAc=5/1) to give Intermediate 8 (232 mg, yield 68%). 1H NMR (CDCl3 300 MHz): δ 9.20 (s, 1H), 7.90 (d, J=9.3 Hz, 1H), 7.40 (dd, J=9.3, 2.7 Hz, 1H), 7.15 (d, J=3.0 Hz, 1H), 3.95 (s, 3H).

Workup

  1. temperaturethe mixture was refluxed for 2 hours
  2. filtrationfiltered off
  3. extractionThe aqueous layer extracted with CH2Cl2 (20 mL×2)
  4. washthe combined organic layer washed with brine (30 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give the crude product, which
  9. customwas purified by silica gel column (PE/EtOAc=5/1)

Sources & evidence

ORD record
ord-3e74961161e0447fa7d112029ce06f43
Source dataset
uspto-grants-2016_06
Patent number
US09364481B2

Reaction notes

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