Triethylamine → HCID 178522068, compound

HRID 491793Notes

Reaction equation

HRID 491793 reaction equation
Cl.[NH2:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([C:9]([NH:11][C:12]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[O:14][C:13]=2[C:21]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=2)=[O:22])=[O:10])[CH2:5][CH2:4]1.C(N(CC)CC)C.I[CH2:39][CH2:40][OH:41]>C(Cl)(Cl)Cl.CO>[OH:41][CH2:40][CH2:39][NH:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([C:9]([NH:11][C:12]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[O:14][C:13]=2[C:21]([NH:23][C:24]2[CH:25]=[CH:26][C:27]([Cl:30])=[CH:28][CH:29]=2)=[O:22])=[O:10])[CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 12225Iodoethanol3×HCID 178479261HCID 178479261, compound

Product 1

HCID 178522068HCID 178522068, compound

Reagents, catalysts & solvents 1

HCID 21584188Chloroform methanolSolvent

Procedure

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).

Workup

  1. temperatureThe reaction solution is cooled with ice
  2. stirringthe mixture is stirred at 50° C. for 3 hours
  3. stirringthe mixture is stirred at 50° C. for 3 hours
  4. stirringthe mixture is further stirred at 50° C. for 15 hours
  5. concentrationThe reaction solution is concentrated under reduced pressure
  6. additionto the residue are poured water
  7. extractiona saturated aqueous sodium hydrogen carbonate solution, and the mixture is extracted with chloroform
  8. washThe organic layer is washed with water
  9. dry with materiala saturated brine, dried over sodium sulfate
  10. customthe solvent is evaporated under reduced pressure
  11. customThe resulting residue is purified by NH-silica gel column chromatography (eluent

Sources & evidence

ORD record
ord-d21abf4d921343bf9280eb1cc9408450
Source dataset
uspto-grants-2009_05
Patent number
US07531537B2

Reaction notes

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