Phosphorus oxychloride → HCID 89782177, compound
Reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[NH:10][C:9](=O)[N:8]([CH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1)[C:7]2=[O:19].P(Cl)(Cl)([Cl:22])=O.C(N(C(C)C)C(C)C)C.C([O-])(O)=O.[Na+]>>[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([Cl:22])[N:8]([CH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1)[C:7]2=[O:19]Participants
Conditions
- Temperature
- 90 °C
Procedure
A mixture of 8-bromo-3-(tetrahydro-2H-pyran-4-yl)quinazoline-2,4(1H,3H)-dione (515b, 1.67 g, 5.14 mmol), phosphoryl trichloride (4.70 mL, 51.4 mmol), and N-ethyl-N-isopropylpropan-2-amine (3.58 mL, 20.54 mmol) was stirred at 90° C. for 20 h. The reaction mixture was concentrated to give a brown oil. Ice was added until the mixture began to stir, and NaHCO3 was added to the mixture; a brown solid which formed was filtered and washed with water. The solid was dissolved in DCM, placed in a separatory funnel, separated, dried over Na2SO4, and concentrated to give 8-bromo-2-chloro-3-(tetrahydro-2H-pyran-4-yl)quinazolin-4(3H)-one (515c, 1.60 g, 4.66 mmol, 91% yield over two steps) as a brown solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.70 (dd, J=12.23, 2.25 Hz, 2H) 3.00 (qd, J=12.36, 4.79 Hz, 2H) 3.51 (td, J=11.93, 1.76 Hz, 2H) 4.14 (dd, J=11.54, 4.69 Hz, 2H) 5.05-5.19 (m, 1H) 7.33 (t, J=7.92 Hz, 1H) 8.00 (dd, J=7.73, 1.27 Hz, 1H) 8.18 (dd, J=8.02, 1.37 Hz, 1H). MS (ESI, pos. ion) m/z: 343.0/344.9 (M+1).
Workup
- concentrationThe reaction mixture was concentrated
- customto give a brown oil
- additionIce was added until the mixture
- stirringto stir
- customa brown solid which formed
- filtrationwas filtered
- washwashed with water
- dissolutionThe solid was dissolved in DCM
- customplaced in a separatory funnel
- customseparated
- dry with materialdried over Na2SO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-9587c7a03fc745e4968795a6adc9d861
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09394297B2
Reaction notes
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