Phosphorus oxychloride → 4-Chloro-5-(ethyloxy)-7-(methyloxy)quinazoline

HRID 536065Notes

Reaction equation

HRID 536065 reaction equation
[CH2:1]([O:3][C:4]1[CH:13]=[C:12]([O:14][CH3:15])[CH:11]=[C:10]2[C:5]=1[C:6](=O)[N:7]=[CH:8][NH:9]2)[CH3:2].O=P(Cl)(Cl)[Cl:19]>CN(C=O)C>[Cl:19][C:6]1[C:5]2[C:10](=[CH:11][C:12]([O:14][CH3:15])=[CH:13][C:4]=2[O:3][CH2:1][CH3:2])[N:9]=[CH:8][N:7]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178467012HCID 178467012, compound

Product 1

HCID 866700324-Chloro-5-(ethyloxy)-7-(methyloxy)quinazolineYield 84.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideCatalyst

Conditions

Temperature
100 °C

Procedure

A mixture of 5-(ethyloxy)-7-(methyloxy)-4(1H)-quinazolinone (285 mg, 1.29 mmol) in POCl3 (10 mL, 107 mmol) was treated with 1 drop of DMF and stirred at 100° C. for 1 hour before being concentrated. The residue was treated with saturated aqueous NaHCO3 and extracted with CH2Cl2. The organic extracts were dried (sodium sulfate), concentrated, and subjected to flash chromatography (1-3% MeOH—CH2Cl2) to give 4-chloro-5-(ethyloxy)-7-(methyloxy)quinazoline (260 mg, 84%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.84 (s, 1 H), 7.03 (d, J=2.51 Hz, 1 H), 6.84 (d, J=2.26 Hz, 1 H), 4.22 (q, J=6.86 Hz, 2 H), 3.96 (s, 3 H), 1.47 (t, J=6.90 Hz, 3 H). MS (m/z) 239.0 (M+H+).

Workup

  1. concentrationbefore being concentrated
  2. additionThe residue was treated with saturated aqueous NaHCO3
  3. extractionextracted with CH2Cl2
  4. dry with materialThe organic extracts were dried (sodium sulfate)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-e8e7e44c36e54e6baa79cd8bc4da9ada
Source dataset
uspto-grants-2014_10
Patent number
US08859571B2

Reaction notes

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