Sodium Carbonate → HCID 178484564, compound

HRID 491791Notes

Reaction equation

HRID 491791 reaction equation
[CH3:1][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:29]=[CH:28][C:27]([Cl:30])=[CH:26][N:25]=2)=[O:22])=[O:10])[CH2:5][CH2:4]1.I[CH2:32][CH2:33][OH:34].C(=O)([O-])[O-].[Na+].[Na+]>C(O)C>[OH:34][CH2:33][CH2:32][N:2]([C@H:3]1[CH2:4][CH2:5][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][N:25]=2)=[O:22])=[O:10])[CH2:7][CH2:8]1)[CH3:1]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 12225Iodoethanol3×HCID 178484809HCID 178484809, compound

Product 1

HCID 178484564HCID 178484564, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

Trans-3-[4-(methylamino)cyclohexylcarbonylamino]-N-(5-chloropyridin-2-yl)benzofuran-2-carboxamide (125 mg) obtained in Example 221 is suspended in ethanol (5 ml), and thereto are added 2-iodo-ethanol (105 μl) and sodium carbonate (57 mg), and the mixture is stirred at 50° C. for 15 hours. To the mixture is further added 2-iodo-ethanol (53 μl), and the mixture is further stirred at 80° C. for 6 hours. Again, 2-iodo-ethanol (53 μl) is added thereto, and the mixture is stirred at 80° C. for 24 hours. The reaction solution is concentrated under reduced pressure, and to the residue is poured a saturated aqueous sodium hydrogen carbonate solution, and the mixture is extracted with chloroform. The organic layer is washed with water, 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: n-hexane/ethyl acetate=1/2, then ethyl acetate) to give trans-3-[4-(N-(2-hydroxyethyl)-N-methylamino)cyclohexylcarbonylamino]-N-(5-chloropyridin-2-yl)benzofuran-2-carboxamide (53 mg). Subsequently, this product 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. The resulting residue is suspended in diethyl ether, and collected by filtration to give the title compound (55 mg).

Workup

  1. stirringthe mixture is further stirred at 80° C. for 6 hours
  2. stirringthe mixture is stirred at 80° C. for 24 hours
  3. concentrationThe reaction solution is concentrated under reduced pressure
  4. additionto the residue is poured a saturated aqueous sodium hydrogen carbonate solution
  5. extractionthe mixture is extracted with chloroform
  6. washThe organic layer is washed with water
  7. dry with materiala saturated brine, dried over sodium sulfate
  8. customthe solvent is evaporated under reduced pressure
  9. customThe resulting residue is purified by NH-silica gel column chromatography (eluent

Sources & evidence

ORD record
ord-dce8d7327c654c4eb559f85c8c8b9247
Source dataset
uspto-grants-2009_05
Patent number
US07531537B2

Reaction notes

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