Imidazole → HCID 178497419, compound

HRID 491784Notes

Reaction equation

HRID 491784 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C(N([CH2:11][CH3:12])CC)C.C(Cl)(=O)[C:14](Cl)=[O:15].[ClH:19].[CH3:20][O:21][C:22]([C:24]1[CH:25]=[CH:26][C:27]2[O:31][C:30]([C:32](NC3C=CC(Cl)=CN=3)=[O:33])=[C:29]([NH:42][C:43]([C@H:45]3[CH2:50][CH2:49][C@H:48]([NH:51][CH3:52])[CH2:47][CH2:46]3)=[O:44])[C:28]=2[CH:53]=1)=[O:23]>C(Cl)(Cl)Cl.C(O)=O>[CH:14]([N:51]([C@H:48]1[CH2:47][CH2:46][C@H:45]([C:43]([NH:42][C:29]2[C:28]3[CH:53]=[C:24]([C:22]([O:21][CH3:20])=[O:23])[CH:25]=[CH:26][C:27]=3[O:31][C:30]=2[C:32]([NH:3][C:2]2[CH:12]=[CH:11][C:4]([Cl:19])=[CH:5][N:1]=2)=[O:33])=[O:44])[CH2:50][CH2:49]1)[CH3:52])=[O:15]

Participants

7

Reactant 4

HCID 795ImidazoleHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 178484810HCID 178484810, compound

Product 1

HCID 178497419HCID 178497419, compound

Reagents, catalysts & solvents 2

HCID 284Formic AcidSolventHCID 6212ChloroformSolvent2×

Procedure

To a solution of imidazole (783 mg) and triethylamine (2.41 ml) in chloroform (80 ml) is added dropwise formic acid (709 μl) with stirring under ice-cooling. Oxalyl chloride (1.00 ml) in chloroform (10 ml) is further added thereto, and the mixture is stirred at room temperature for 0.5 hour. The reaction solution is cooled again with ice, and thereto is added trans-5-methoxycarbonyl-3-[4-(methylamino)cyclohexylcarbonylamino]-N-(5-chloropyridine-2-yl)benzofuran-2-carboxamide hydrochloride (1.50 g) obtained in Example 218. The mixture is warmed to room temperature and stirred for 3 hours. To the reaction solution are poured ice-water and a saturated aqueous sodium hydrogen carbonate solution, and the mixture is extracted with chloroform. The extract is washed with a saturated brine, and dried over sodium sulfate. The solvent is evaporated under reduced pressure, and the resulting residue is purified by NH-silica gel column chromatography (eluent: chloroform) to give the title compound (1.45 g).

Workup

  1. temperaturecooling
  2. stirringthe mixture is stirred at room temperature for 0.5 hour
  3. temperatureThe reaction solution is cooled again with ice
  4. stirringstirred for 3 hours
  5. extractiona saturated aqueous sodium hydrogen carbonate solution, and the mixture is extracted with chloroform
  6. washThe extract is washed with a saturated brine
  7. dry with materialdried over sodium sulfate
  8. customThe solvent is evaporated under reduced pressure
  9. customthe resulting residue is purified by NH-silica gel column chromatography (eluent: chloroform)

Sources & evidence

ORD record
ord-19160bea9d94499c92397cfe57527252
Source dataset
uspto-grants-2009_05
Patent number
US07531537B2

Reaction notes

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