Phosphorus oxychloride → 4-Chloro-2-(difluoro(5-fluoropyridin-2-yl)methyl)-7-methoxyquinazoline
반응식
[F:1][C:2]([F:23])([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][N:17]=1)[C:3]1[NH:12][C:11](=O)[C:10]2[C:5](=[CH:6][C:7]([O:14][CH3:15])=[CH:8][CH:9]=2)[N:4]=1.CCN(C(C)C)C(C)C.P(Cl)(Cl)([Cl:35])=O>>[Cl:35][C:11]1[C:10]2[C:5](=[CH:6][C:7]([O:14][CH3:15])=[CH:8][CH:9]=2)[N:4]=[C:3]([C:2]([F:23])([F:1])[C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][N:17]=2)[N:12]=1참가 물질
반응 조건
- 온도
- 115 °C
실험 절차
To 2-(difluoro(5-fluoropyridin-2-yl)methyl)-7-methoxyquinazolin-4(3H)-one (480 mg, 1.5 mmol) were added DIEA (0.55 mL, 3.0 mmol) and phosphorous oxychloride (10 mL, 108 mmol), and the mixture was heated at 115° C. for 6 h. The mixture was allowed to cool to rt and was concentrated under reduced pressure. Toluene was added and evaporated twice to remove residual phosphorous oxychloride. 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) and brine (2×10 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to afford 4-chloro-2-(difluoro(5-fluoropyridin-2-yl)methyl)-7-methoxyquinazoline as a brown viscous oil (500 mg).
후처리
- temperatureto cool to rt
- concentrationwas concentrated under reduced pressure
- additionToluene was added
- customevaporated twice
- customto remove residual phosphorous oxychloride
- 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) and brine (2×10 mL)
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated under reduced pressure
출처 및 근거
- ORD 기록
- ord-de4211c0c2d842cb975cec09def755e8
- 출처 데이터셋
- uspto-grants-2014_01
- 특허 번호
- US08633207B2
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