Formamide → 4-Chloroquinazoline

HRID 487577Notes

Reaction equation

HRID 487577 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[N:3][CH:2]=1.C(N)=O.CN(C=NC=[N+](C)C)C.[Cl-].OC1C2C(=CC=CC=2)N=CN=1.P(Cl)(Cl)(Cl)(Cl)[Cl:36]>O1CCOCC1.P(Cl)(Cl)(Cl)=O>[Cl:36][C:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[N:1]=[CH:2][N:3]=1

Participants

8

Reactant 5

HCID 713FormamideHCID 9210QuinazolineHCID 24819Phosphorus pentachlorideHCID 11008255Gold's ReagentHCID 178517962HCID 178517962, compound

Product 1

HCID 788644-Chloroquinazoline

Reagents, catalysts & solvents 2

HCID 24813Phosphorus oxychlorideSolventHCID 312751,4-DioxaneSolvent

Procedure

Quinazoline starting materials are commercially available or readily prepared using conventional procedures. For example, 4-hydroxy quinazolines can be prepared from commercially available anthranilic acids via condensation with excess formamide at reflux (M. Endicott et al. J. Am. Chem. Soc., 1946, 68, 1299). Alternatively hydroxy quinazolines can be prepared in dioxane at reflux using Gold's reagent (J. Gupton; Correia, K.; Hertel, G. Synthetic Communications, 1984, 14, 1013). Once in hand, the 4-hydroxy quinazoline is chlorinated under standard conditions, using for example phosphorus pentachloride in phosphorus oxychloride, to provide 4-chloroquinazoline starting materials. The 4-hydroxy quinazoline derivatives can advantageously be chlorinated using the chlorinating reagents and procedure disclosed in U.S. Pat. No. 4,230,644.

Workup

  1. customreadily prepared
  2. temperatureat reflux (M. Endicott et al. J. Am. Chem. Soc., 1946, 68, 1299)
  3. temperatureat reflux

Sources & evidence

ORD record
ord-6a3211e780de4b41a12fb9630be8eae3
Source dataset
uspto-grants-1994_03
Patent number
US05296484

Reaction notes

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