Sodium Iodide → HCID 178522095, compound

HRID 491794Notes

Reaction equation

HRID 491794 reaction equation
Cl.Cl.[NH2:3][C@H:4]1[CH2:9][CH2:8][C@H:7]([C:10]([NH:12][C:13]2[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=3[O:15][C:14]=2[C:22]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][N:26]=2)=[O:23])=[O:11])[CH2:6][CH2:5]1.Cl[CH2:33][CH2:34][O:35][CH2:36][CH2:37]Cl.[I-].[Na+].C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C(=O)C>[N:3]1([C@H:4]2[CH2:9][CH2:8][C@H:7]([C:10]([NH:12][C:13]3[C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=4[O:15][C:14]=3[C:22]([NH:24][C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][N:26]=3)=[O:23])=[O:11])[CH2:6][CH2:5]2)[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 8115Bis(2-chloroethyl) ether2×HCID 10340Sodium CarbonateHCID 178478721HCID 178478721, compound

Product 1

HCID 178522095HCID 178522095, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
50 °C

Procedure

Trans-3-[4-aminocyclohexylcarbonylamino]-N-(5-chloropyridin-2-yl)benzofuran-2-carboxamide dihydrochloride (200 mg) obtained in Example 219 is suspended in N,N-dimethyl acetamide (10 ml), and thereto are added bis(2-chloroethyl) ether (73 μl), sodium iodide (185 mg), and sodium carbonate (131 mg), and the mixture is stirred at 50° C. for 5 hours, and then stirred at 80° C. for 3 hours. Bis(2-chloroethyl) ether (73 μl) is further added thereto, and the mixture is stirred at 80° C. for 15 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 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: n-hexane/ethyl acetate=5/1, then 1/1) to give trans-3-[4-(morpholin-4-yl)cyclohexylcarbonylamino]-N-(5-chloropyridin-2-yl)benzofuran-2-carboxamide (70 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), and the solvent is evaporated under reduced pressure. The resulting residue is suspended in diethyl ether, and collected by filtration to give the title compound (65 mg).

Workup

  1. stirringstirred at 80° C. for 3 hours
  2. stirringthe mixture is stirred at 80° C. for 15 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-88c7fb1c7c464881930802d5e175255d
Source dataset
uspto-grants-2009_05
Patent number
US07531537B2

Reaction notes

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