Phosphorus oxychloride → 4-Chloroquinazoline-2-carbonitrile

HRID 41358Notes

Reaction equation

HRID 41358 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-7ac932ce2e20475a94c100ab752e386e
Source dataset
uspto-grants-2013_09
Patent number
US08530652B2

Reaction notes

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