Phosphorus oxychloride → 4-Chloro-7-isopropylquinazoline
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]=1Participants
3
Procedure
The product of Example 431E (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).