Glutaraldehyde → HCID 178522094, compound

HRID 491796Notes

Reaction equation

HRID 491796 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.[CH:32](=O)[CH2:33][CH2:34][CH2:35][CH:36]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>ClCCl.C(N(CC)CC)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)[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1

Participants

7

Reactant 4

HCID 3485GlutaraldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 178478721HCID 178478721, compound

Product 1

HCID 178522094HCID 178522094, compoundYield 85.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

Trans-3-(4-aminocyclohexylcarbonylamino)-N-(5-chloropyridin-2-yl)benzofuran-2-carboxamide dihydrochloride (125 mg) obtained in Example 219 is suspended in dichloromethane (10 ml), and thereto is added triethylamine (102 μl) under ice-cooling, and the mixture is stirred for several minutes. Then, about 25% aqueous glutaraldehyde solution (150 mg) and sodium triacetoxy borohydride (155 mg) are added successively, and the mixture is stirred under ice-cooling for 2 hours. To the reaction solution is poured a saturated aqueous sodium hydrogen carbonate solution, and the mixture is extracted with chloroform. The organic layer is washed successively 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=3/1, then 1/1) to give trans-3-[4-(piperidin-1-yl)cyclohexylcarbonylamino]-N-(5-chloropyridin-2-yl)benzofuran-2-carboxamide (106 mg). Subsequently, this product is dissolved in chloroform/methanol (5/1, 6 ml), and 4N hydrogen chloride in ethyl acetate (5 ml) is added thereto under ice-cooling. The reaction solution is concentrated under reduced pressure, and the resulting residue is suspended in diethyl ether, and collected by filtration to give the title compound (107 mg).

Workup

  1. temperaturecooling
  2. stirringthe mixture is stirred under ice-
  3. temperaturecooling for 2 hours
  4. extractionthe mixture is extracted with chloroform
  5. washThe organic layer is washed successively with water
  6. dry with materiala saturated brine, dried over sodium sulfate
  7. customthe solvent is evaporated under reduced pressure
  8. customThe resulting residue is purified by NH-silica gel column chromatography (eluent

Sources & evidence

ORD record
ord-ef9f451ec58b4192b62dedfb623a4482
Source dataset
uspto-grants-2009_05
Patent number
US07531537B2

Reaction notes

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