Phosphorus oxychloride → 4-Chloroquinazoline-2-carbonitrile

HRID 563895Notes

Reaction equation

HRID 563895 reaction equation
O=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]([NH2:14])=O)[NH:3]1.O=P(Cl)(Cl)[Cl:17]>>[Cl:17][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]#[N:14])[N:3]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 135780260HCID 135780260, compound

Product 1

HCID 552771384-Chloroquinazoline-2-carbonitrileYield 62%

Procedure

4-Oxo-3,4-dihydroquinazoline-2-carboxamide (40b, 0.51 g, 2.69 mmol) was heated to 100° C. in POCl3 (7.0 mL) for three hours. The solvent was removed under reduced pressure. Ice-cold water was carefully added to the flask, and the insoluble product was filtered off. The filtrate was extracted three times with chloroform. The combined organics were dried (MgSO4) and evaporated to give 4-Chloroquinazoline-2-carbonitrile (40c, 0.21 g). 95% pure by HPLC and used without further purification. The insoluble product was purified by flash silica gel chromatography eluting with 3-30% EtOAc/hexane to give an additional 0.22 g of 40c as a white solid for an overall yield of 62%. Rf=0.53 (30% EtOAc/hexane). 1H NMR (400 MHz, DMSO-d6): δ 8.07-8.11 (m, 1H), 8.24-8.31 (m, 2H), 8.41 (d, J=8.4 Hz, 1H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionIce-cold water was carefully added to the flask
  3. filtrationthe insoluble product was filtered off
  4. extractionThe filtrate was extracted three times with chloroform
  5. dry with materialThe combined organics were dried (MgSO4)
  6. customevaporated

Sources & evidence

ORD record
ord-092413d4b723465c983a3b11be466ba4
Source dataset
uspto-grants-2011_11
Patent number
US08067591B2

Reaction notes

Loading…