Thionyl Chloride → 7-(Benzyloxy)-4-chloroquinazoline

HRID 871331Notes

Reaction equation

HRID 871331 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](=O)[NH:14][CH:15]=[N:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)([Cl:22])=O>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([Cl:22])=[N:14][CH:15]=[N:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 1357631107-(Benzyloxy)-3,4-dihydroquinazolin-4-one

Product 1

HCID 220309237-(Benzyloxy)-4-chloroquinazolineYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

7-(Benzyloxy)quinazolin-4(3H)-one (5 g, 19.8 mmol) was treated with thionyl chloride (50 mL) and anhydrous N,N′-dimethylformamide (0.5 mL) and heated to 80° C. for 1.5 h. The solvent was removed under reduced pressure and the residue dissolved in dichloromethane, cooled to 0° C. and the pH adjusted to basic (pH=8) with a saturated solution of sodium bicarbonate. The organic layer was separated, the water extracted with ethyl acetate and the organics combined, dried (MgSO4) and concentrated under reduced pressure to give 7-(benzyloxy)-4-chloroquinazoline (4.75 g, 89%), which was used directly in the next step without further purification. 1H NMR (300 MHz, DMSO-d6) δ 9.13 (s, 1H), 8.18 (d, 1H), 7.97-7.46 (m, 4H), 7.46-7.35 (m, 4H), 5.35 (s, 2H); LC-MS (ESI) m/z 271 (M+H)+.

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue dissolved in dichloromethane
  3. temperaturecooled to 0° C.
  4. customThe organic layer was separated
  5. extractionthe water extracted with ethyl acetate
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9604481d182f44c78378aa241281af00
Source dataset
uspto-grants-2015_03
Patent number
US08969587B2

Reaction notes

Loading…