Phosphorus oxychloride → 4-Chloro-7-isopropylquinazoline

HRID 884003Notes

Reaction equation

HRID 884003 reaction equation
[CH:1]([C:4]1[CH:13]=[C:12]2[C:7]([C:8](=O)[NH:9][CH:10]=[N:11]2)=[CH:6][CH:5]=1)([CH3:3])[CH3:2].P(Cl)(Cl)([Cl:17])=O>>[Cl:17][C:8]1[C:7]2[C:12](=[CH:13][C:4]([CH:1]([CH3:3])[CH3:2])=[CH:5][CH:6]=2)[N:11]=[CH:10][N:9]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 1361233184-Hydroxy-7-isopropylquinazoline

Product 1

HCID 866155654-Chloro-7-isopropylquinazolineYield 97%

Procedure

The product of Example 91E (100 mg, 0.5313 mmol) in phosphorous oxychloride (2 mL) was heated under a nitrogen atmosphere at reflux for one hour. The reaction was cooled and concentrated by rotary evaporation. The residue was dissolved in ethyl acetate (50 mL) and washed sequentially with saturated aqueous sodium hydrogencarbonate (2×25 mL), water (25 mL), and brine (25 mL). The organic extract was dried over sodium sulfate, filtered, and concentrated by rotary evaporation to afford the title compound as a yellow oil (107 mg, 0.5177 mmol, 97%). 1H NMR (300 MHz, DMSO-D6) δ ppm 1.33 (d, J=6.99 Hz, 6 H) 3.14-3.29 (m, 1 H) 7.86 (dd, J=8.64, 1.65 Hz, 1 H) 7.93 (s, 1 H) 8.22 (d, J=8.46 Hz, 1 H) 9.07 (s, 1 H).

Workup

  1. temperatureat reflux for one hour
  2. temperatureThe reaction was cooled
  3. concentrationconcentrated by rotary evaporation
  4. dissolutionThe residue was dissolved in ethyl acetate (50 mL)
  5. washwashed sequentially with saturated aqueous sodium hydrogencarbonate (2×25 mL), water (25 mL), and brine (25 mL)
  6. extractionThe organic extract
  7. dry with materialwas dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated by rotary evaporation

Sources & evidence

ORD record
ord-44dda497ebf14870bee03c5d074352b6
Source dataset
uspto-grants-2012_08
Patent number
US08236950B2

Reaction notes

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