反応式
Cl.[O:2]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[O:5][CH2:4][CH:3]1[CH2:12][NH2:13].[F:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[NH:20][CH:19]=[C:18]2[CH2:24][CH2:25][CH2:26]Br.C(N(C(C)C)CC)(C)C>CN(C=O)C>[O:2]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[O:5][CH2:4][CH:3]1[CH2:12][NH:13][CH2:26][CH2:25][CH2:24][C:18]1[C:17]2[C:21](=[CH:22][CH:23]=[C:15]([F:14])[CH:16]=2)[NH:20][CH:19]=1参加物
反応条件
- 温度
- 80 °C
実験手順
2,3-Dihydro-1,4-benzodioxin-2-methanamine hydrochloride (2.0 g, 10.0 mmole) in DMF (100 ml) was slowly added to the mixture of 5-fluoro-3-(3-bromopropyl)indole (2.6 g, 10.0 mmole) and diisopropylethylamine (8.7 ml, 50 mmole) in 100 ml of DMF with stirring and the mixture was heated at 80° C. for 24 hours. Most of DMF was removed and the residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The dichloromethane solution was dried over anhydrous sodium sulfate, filtered, concentrated in vacuum and column chromatographed on silica gel using ethyl acetate as the eluant. The combined fractions of free base of the expected product (0.5 g, 1.6 mmole, 15%) were concentrated, dissolved in 50 ml of ethanol-diethyl ether (1:1). To this was added 0.25M of fumaric acid in ethanol (3.4 ml, 0.85 mmole) and then a minimum amount of hexane to precipitate the title compound as a light tan solid, (2:1) fumarate salt, m.p. 186°-188° C.
後処理
- customMost of DMF was removed
- customthe residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate
- dry with materialThe dichloromethane solution was dried over anhydrous sodium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuum and column
- customchromatographed on silica gel
出典と根拠
- ORDレコード
- ord-256bff101f164c5b965c778f18544fa1
- 出典データセット
- uspto-grants-1998_05
- 特許番号
- US05750724
関連ノート
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