Phosphorus oxychloride → 4-Chloro-6-ethoxy-7-methoxyquinazoline

HRID 536063Notes

Reaction equation

HRID 536063 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[NH:10][CH:9]=[N:8][C:7]2=O)[CH3:2].O=P(Cl)(Cl)[Cl:19]>CN(C=O)C>[Cl:19][C:7]1[C:6]2[C:11](=[CH:12][C:13]([O:14][CH3:15])=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=2)[N:10]=[CH:9][N:8]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178465841HCID 178465841, compound

Product 1

HCID 109226204-Chloro-6-ethoxy-7-methoxyquinazolineYield 69%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideCatalyst

Conditions

Temperature
100 °C

Procedure

A mixture of 6-(ethyloxy)-7-(methyloxy)-4(1H)-quinazolinone (560 mg, 2.54 mmol) in POCl3 (5 mL, 53.6 mmol) was treated with 1 drop of DMF and heated at 100° C. for 2 hours before being concentrated. The residue was treated with saturated aqueous NaHCO3 and extracted with CH2Cl2. The organic extracts were dried (sodium sulfate) and concentrated to give 4-chloro-6-(ethyloxy)-7-(methyloxy)quinazoline (416 mg, 1.74 mmol, 69%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.88 (s, 1 H), 7.46 (s, 1 H), 7.39 (s, 1 H), 4.26 (q, J=6.94 Hz, 2 H), 4.02 (s, 3 H), 1.44 (t, J=7.03 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-8b14e35b71d64145b270409cf07b484f
Source dataset
uspto-grants-2014_10
Patent number
US08859571B2

Reaction notes

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