Phosphorus oxychloride → HCID 86662697, compound
Reaction equation
[F:1][C:2]([F:22])([C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][N:16]=1)[C:3]1[NH:12][C:11](=O)[C:10]2[C:5](=[C:6]([Br:14])[CH:7]=[CH:8][CH:9]=2)[N:4]=1.CCN(C(C)C)C(C)C.O=P(Cl)(Cl)[Cl:34]>>[Cl:34][C:11]1[C:10]2[C:5](=[C:6]([Br:14])[CH:7]=[CH:8][CH:9]=2)[N:4]=[C:3]([C:2]([F:22])([F:1])[C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][N:16]=2)[N:12]=1Participants
Conditions
- Temperature
- 115 °C
Procedure
To 2-[difluoro-(5-fluoro-pyridin-2-yl)-methyl]-8-bromo-3H-quinazolin-4-one (0.19 g, 0.52 mmol) at rt were added DIEA (0.18 mL, 1.04 mmol) and POCl3 (3.5 mL, 76 mmol) and the mixture was heated at 115° C. for 6 h. The mixture was allowed to cool to rt and then was concentrated under reduced pressure. The residue was treated with toluene and concentrated to dryness twice. The residue was partitioned between EtOAc (20 mL) and cold saturated aq NaHCO3 (10 mL), and the separated EtOAc layer was diluted with EtOAc (60 mL) and washed with saturated aq NaHCO3 (10 mL), brine (2×10 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to afford 4-chloro-2-[difluoro-(5-fluoro-pyridin-2-yl)-methyl]-8-bromo-quinazoline as a brown viscous oil (207 mg, quantitative).
Workup
- temperatureto cool to rt
- concentrationwas concentrated under reduced pressure
- additionThe residue was treated with toluene
- concentrationconcentrated to dryness twice
- customThe residue was partitioned between EtOAc (20 mL) and cold saturated aq NaHCO3 (10 mL)
- additionthe separated EtOAc layer was diluted with EtOAc (60 mL)
- washwashed with saturated aq NaHCO3 (10 mL), brine (2×10 mL)
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-4ecfe9c04435440ea8c77b1753895f77
- Source dataset
- uspto-grants-2014_01
- Patent number
- US08633207B2
Reaction notes
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