1,2-Dichloroethane → 4-Chloro-6,7-dimethoxyquinazoline

HRID 1784379Notes

Reaction equation

HRID 1784379 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2O.C(NC(C)C)(C)C.[Cl:23]CCCl>>[Cl:23][C:6]1[C:5]2[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]=[CH:8][N:7]=1

Participants

4

Reactant 3

HCID 111,2-DichloroethaneHCID 7912DiisopropylamineHCID 178486869HCID 178486869, compound

Product 1

HCID 27693644-Chloro-6,7-dimethoxyquinazolineYield 88.9%

Conditions

Temperature
80 °C

Procedure

To a suspension of 6,7-Dimethoxy-quinazolin-4-ol (1.65 g, 8.0 mmol) and phosporousoxychloride (1.52 ml, 16.4 mmol) in 1,2-dichloroethane (16 ml) was added diisopropylamine (3.48 ml, 20 mmol) in a dropwise fashion. The mixture was then heated to 80° C. under an inert atmosphere for 16 hours. After this time the reaction was cooled to room temperature and concentrated in vacuo to dryness, dissolved in CH2Cl2 (50 ml) and washed with sodium bicarbonate solution (5% aqueous, 2*25 ml). The organic layer was separated, dried using MgSO4, filtered and concentrated in vacuo to give a brown residue that was purified by flash chromatography (SiO2) eluted with CH2Cl2:EtOAc—2:98 then 5:95 to give the title compound (1.6 g, 88.9%) as a yellow solid. m/z (LC-MS, ESP): 207 [M+H]+, R/T=3.51 mins

Workup

  1. temperatureAfter this time the reaction was cooled to room temperature
  2. concentrationconcentrated in vacuo to dryness
  3. dissolutiondissolved in CH2Cl2 (50 ml)
  4. washwashed with sodium bicarbonate solution (5% aqueous, 2*25 ml)
  5. customThe organic layer was separated
  6. customdried
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a brown residue that
  10. customwas purified by flash chromatography (SiO2)
  11. washeluted with CH2Cl2

Sources & evidence

ORD record
ord-ee1961e04388462793459e5e4568c33e
Source dataset
uspto-grants-2009_03
Patent number
US07504397B2

Reaction notes

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