Phosphorus oxychloride → 4-Chloro-2-chloromethyl-7-(3-trifluoromethyl-pyridin-2-yl)-quinazoline

HRID 2113612Notes

Reaction equation

HRID 2113612 reaction equation
[Cl:1][CH2:2][C:3]1[NH:12][C:11](=O)[C:10]2[C:5](=[CH:6][C:7]([C:14]3[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][CH:17]=[CH:16][N:15]=3)=[CH:8][CH:9]=2)[N:4]=1.O=P(Cl)(Cl)[Cl:26]>>[Cl:26][C:11]1[C:10]2[C:5](=[CH:6][C:7]([C:14]3[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][CH:17]=[CH:16][N:15]=3)=[CH:8][CH:9]=2)[N:4]=[C:3]([CH2:2][Cl:1])[N:12]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 1356820662-chloromethyl-7-(3-trifluoromethyl-pyridin-2-yl)-3H-quinazolin-4-one

Product 1

HCID 220301504-Chloro-2-chloromethyl-7-(3-trifluoromethyl-pyridin-2-yl)-quinazoline

Procedure

Reflux a mixture of 2-chloromethyl-7-(3-trifluoromethyl-pyridin-2-yl)-3H-quinazolin-4-one and POCl3 for 16 hours. Cool the mixture and concentrate under reduced pressure. Partition the residue between EtOAc and saturated NaHCO3 solution. Wash the EtOAc portion with additional NaHCO3 and then dry (Na2SO4) and concentrate under reduced pressure. Filter the brown residue through 2 inches of silica gel (1:1 EtOAc/hexanes eluent) and concentrate under reduced pressure to give 4-chloro-2-chloromethyl-7-(3-trifluoromethyl-pyridin-2-yl)-quinazoline.

Workup

  1. temperatureReflux
  2. temperatureCool the mixture
  3. concentrationconcentrate under reduced pressure
  4. customPartition the residue between EtOAc and saturated NaHCO3 solution
  5. washWash the EtOAc portion with additional NaHCO3
  6. dry with materialdry (Na2SO4)
  7. concentrationconcentrate under reduced pressure
  8. filtrationFilter the brown residue through 2 inches of silica gel (1:1 EtOAc/hexanes eluent)
  9. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-09b40d1231ba47b19d91f2fb61965382
Source dataset
uspto-grants-2008_10
Patent number
US07432275B2

Reaction notes

Loading…