Dimethylformamide → 4-Chloro-7-(2-chloroethoxy)-6-methoxyquinazoline

HRID 1668683Notes

Reaction equation

HRID 1668683 reaction equation
[Cl:1][CH2:2][CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9](=O)[NH:10][CH:11]=[N:12]2)=[CH:7][C:6]=1[O:16][CH3:17].CN(C=O)C.S(Cl)([Cl:25])=O>>[Cl:25][C:9]1[C:8]2[C:13](=[CH:14][C:5]([O:4][CH2:3][CH2:2][Cl:1])=[C:6]([O:16][CH3:17])[CH:7]=2)[N:12]=[CH:11][N:10]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 135589778HCID 135589778, compound

Product 1

HCID 596829074-Chloro-7-(2-chloroethoxy)-6-methoxyquinazolineYield 59%

Conditions

Temperature
80 °C

Procedure

7-(2-Chloroethoxy)-6-methoxy-3,4-dihydroquinazolin-4-one (5 g, 19 mmol) was suspended in thionyl chloride (28 mL) and DMF (0.7 mL) was added. The mixture was heated at 80° C. for 1.5 hours under anhydrous conditions. The excess thionyl chloride was evaporated off and toluene was added to remove the last traces by azeotropic distillation (repeated twice). The solid was suspended in ice-water and the pH adjusted to 7.5 with sodium hydroxide 2N first then with a saturated sodium hydrogen carbonate solution. The solid was collected by filtration, washed with water, ether and dried over P2O5 under vacuum. The crude product was purified by flash chromatography using dichloromethane/acetonitrile (95/5 up to 90/10). Evaporation of the solvent gave 4-chloro-7-(2-chloroethoxy)-6-methoxyquinazoline (3.06 g, 59%).

Workup

  1. customThe excess thionyl chloride was evaporated off
  2. additiontoluene was added
  3. customto remove the last traces
  4. distillationby azeotropic distillation (
  5. filtrationThe solid was collected by filtration
  6. washwashed with water, ether
  7. dry with materialdried over P2O5 under vacuum
  8. customThe crude product was purified by flash chromatography
  9. customEvaporation of the solvent

Sources & evidence

ORD record
ord-f15864c70c484ae093ebd89fc4cdce20
Source dataset
uspto-grants-2011_08
Patent number
US07989460B2

Reaction notes

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