反応 #578975

反応方程式

2-Iodo-ethanol

Trans-3-[4-aminocyclohexylcarbonylamino]-N-(4-chlorophenyl)benzofuran-2-carboxamide hydrochloride

triethylamine

2-iodo-ethanol

2-iodo-ethanol

→

trans-3-[4-(2-hydroxyethylamino)cyclohexylcarbonylamino]-N-(4-chlorophenyl)benzofuran-2-carboxamide

溶媒

acetonitrile methanol

chloroform methanol

反応条件

後処理

1. 1
   温度The reaction solution is cooled with ice
2. 2
   workup.STIRRINGthe mixture is stirred at 50° C. for 3 hours
3. 3
   workup.STIRRINGthe mixture is stirred at 50° C. for 3 hours
4. 4
   workup.STIRRINGthe mixture is further stirred at 50° C. for 15 hours
5. 5
   濃縮The reaction solution is concentrated under reduced pressure
6. 6
   workup.ADDITIONto the residue are poured water
7. 7
   抽出a saturated aqueous sodium hydrogen carbonate solution, and the mixture is extracted with chloroform
8. 8
   洗浄The organic layer is washed with water
9. 9
   乾燥a saturated brine, dried over sodium sulfate
10. 10
    その他the solvent is evaporated under reduced pressure
11. 11
    その他The resulting residue is purified by NH-silica gel column chromatography (eluent

実験手順

Trans-3-[4-aminocyclohexylcarbonylamino]-N-(4-chlorophenyl)benzofuran-2-carboxamide hydrochloride (150 mg) obtained in Example 225 is suspended in acetonitrile/methanol (5/1, 6 ml), and thereto is added triethylamine (93 μl), and the mixture is stirred at room temperature for several minutes. The reaction solution is cooled with ice, and thereto is added 2-iodo-ethanol (29 μl), and the mixture is stirred at 50° C. for 3 hours. 2-Iodo-ethanol (58 μl) is further added thereto, and the mixture is stirred at 50° C. for 3 hours. Again, 2-iodo-ethanol (58 μl) is added thereto, and the mixture is further stirred at 50° C. for 15 hours. The reaction solution is concentrated under reduced pressure, and to the residue are poured water and a saturated aqueous sodium hydrogen carbonate solution, and the mixture is extracted with chloroform. The organic layer is washed with water and a saturated brine, dried over sodium sulfate, and the solvent is evaporated under reduced pressure. The resulting residue is purified by NH-silica gel column chromatography (eluent: ethyl acetate, then ethyl acetate/methanol=20/1) to give trans-3-[4-(2-hydroxyethylamino)cyclohexylcarbonylamino]-N-(4-chlorophenyl)benzofuran-2-carboxamide (104 mg). This product (104 mg) is dissolved in chloroform/methanol (5/1, 6 ml), and thereto is added 4N hydrogen chloride in ethyl acetate (1 ml). The solvent is evaporated under reduced pressure, and the resulting residue is suspended in diethyl ether, and collected by filtration to give the title compound (95 mg).

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