Diisopropylethylamine → (2,3-Dihydro-benzo[1,4]dioxin-2-ylmethyl)-[3-(5-fluoro-1H-indol-3-yl)-propyl]-amine

HRID 1290258

반응식

HRID 1290258 반응식
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

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 28498361,4-Benzodioxan, 2-(aminomethyl)-, hydrochlorideHCID 114026013-(3-bromopropyl)-5-fluoro-1H-indole

생성물 1

HCID 18923899(2,3-Dihydro-benzo[1,4]dioxin-2-ylmethyl)-[3-(5-fluoro-1H-indol-3-yl)-propyl]-amine수율 16%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

반응 조건

온도
80 °C

실험 절차

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.

후처리

  1. customMost of DMF was removed
  2. customthe residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate
  3. dry with materialThe dichloromethane solution was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuum and column
  6. customchromatographed on silica gel

출처 및 근거

ORD 기록
ord-256bff101f164c5b965c778f18544fa1
출처 데이터셋
uspto-grants-1998_05
특허 번호
US05750724

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