反応式
[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[OH:12])[N:8]=[CH:7][C:6]([C:13]#[N:14])=[C:5]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1.Br[CH2:25][CH2:26]Br.C(=O)([O-])[O-].[K+].[K+]>C(OCCO)C>[Cl:23][C:18]1[CH:17]=[C:16]([CH:21]=[CH:20][C:19]=1[F:22])[NH:15][C:5]1[C:4]2[CH:3]=[C:2]3[NH:1][CH2:25][CH2:26][O:12][C:11]3=[CH:10][C:9]=2[N:8]=[CH:7][C:6]=1[C:13]#[N:14]参加物
反応物 3
生成物 1
試薬・触媒・溶媒 1
反応条件
- 温度
- 135 °C
実験手順
An amount of 6-amino-4-(3-chloro-4-fluoro-phenylamino)-7-hydroxy-quinoline-3-carbonitrile (4 g, 12.2 mmol) was stirred in 2-ethoxyethanol (480 mL), and to this were added 1,2-dibromoethane (22.9 g, 12.2 mmol), and potassium carbonate (10.1 g, 73 mmol), and the mixture was heated at 135° C. for 0.5 hours. After cooling to room temperature, the mixture was filtered over a thin silica pad and evaporated to an oil. To this was added ethyl acetate and saturated brine solution, and the layers were separated. The organic layer was dried on sodium sulfate and evaporated to a brown oil. Purification was carried out by flash chromatography (70% ethyl acetate in hexane) to yield a yellow solid (1.95 g, 45% yield), m.p. 244-245° C.; 1H NMR (DMSO-d6) δ 9.32 (s, 1H), 8.29 (s, 1H), 7.36 (m, 2H), 7.19 (s, 1H), 7.12 (m, 2H), 6.59 (s, 1H), 4.27 (m, 2H), 3.37 (m, 2H); HRMS (EI) m/z 355.07512 (M+1). Analysis for C18H12ClFN4.O0.1H2O.0.4CH3CO2C2H5: Found: C, 59.59; H, 3.66; N, 14.69. Calcd: C, 59.97; H, 3.93; N, 14.29.
後処理
- temperatureAfter cooling to room temperature
- filtrationthe mixture was filtered over a thin silica pad
- customevaporated to an oil
- additionTo this was added ethyl acetate and saturated brine solution
- customthe layers were separated
- customThe organic layer was dried on sodium sulfate
- customevaporated to a brown oil
- customPurification
出典と根拠
- ORDレコード
- ord-61a1e7f2c08747c3979ecb5de0eec882
- 出典データセット
- uspto-grants-2003_08
- 特許番号
- US06608048B2
関連ノート
読み込み中…