Ethylenediamine → 5-((2-Aminoethyl)amino)-6-fluoro-3-(1H-pyrrol-2-YL)benzo(CD)indol-2(1H)-one
Reaction equation
[F:1][C:2]1[C:3](/[C:12](/I)=[CH:13]/[C:14](=O)[C:15]2[NH:16][CH:17]=[CH:18][CH:19]=2)=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[CH2:5]2.[H-].[Na+].[CH2:24]([NH2:27])[CH2:25][NH2:26]>>[NH2:26][CH2:25][CH2:24][NH:27][C:12]1[CH:13]=[C:14]([C:15]2[NH:16][CH:17]=[CH:18][CH:19]=2)[C:5]2[C:6](=[O:11])[NH:7][C:8]3[C:4]=2[C:3]=1[C:2]([F:1])=[CH:10][CH:9]=3Participants
Procedure
To a suspension of (Z)-5-fluoro-4-[1-iodo-3-oxo-3-(1H-pyrrol-2-yl)-propenyl]-1,3-dihydro-indol-2-one (from Example 8 above) (1.58 g, 4.0 mmol) in ethylenediamine (Aldrich, 70 mL) was added NaH (Aldrich, 95%, 1.0 g, 40 mmol) in small portions at room temperature. After stirring at room temperature for 30 minutes, the reaction mixture was heated to 120° C. for 1.5 hours. The reaction was quenched by pouring the reaction mixture into an ice-cold saturated aqueous ammonium chloride solution (200 mL) and extracted with ethyl acetate (3×150 mL). The combined organic extracts were successively washed with water (100 mL) and brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give crude 5-(2-amino-ethylamino)-6-fluoro-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one as a brown solid. (Yield 1.1 g, 88.7%).
Workup
- temperaturethe reaction mixture was heated to 120° C. for 1.5 hours
- customThe reaction was quenched
- additionby pouring the reaction mixture into an ice-cold saturated aqueous ammonium chloride solution (200 mL)
- extractionextracted with ethyl acetate (3×150 mL)
- washThe combined organic extracts were successively washed with water (100 mL) and brine (100 mL)
- dry with materialdried over anhydrous sodium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-de584b8785364f73b71e2c12c625a520
- Source dataset
- uspto-grants-2003_03
- Patent number
- US06531598B1
Reaction notes
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