Trimethyl orthoformate → N'-({1-[4-(dipropylamino)butyl]-4-piperidinyl}methyl)-N,N-bis(1H-imidazol-2-ylmethyl)urea

HRID 1920130Notes

Reaction equation

HRID 1920130 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH2:6][N:7]([CH2:18][C:19]1[NH:20][CH:21]=[CH:22][N:23]=1)[C:8]([NH:10][CH2:11][CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1)=[O:9].[CH2:24]([N:27]([CH2:33][CH2:34][CH3:35])[CH2:28][CH2:29][CH2:30][CH:31]=O)[CH2:25][CH3:26].C(OC)(OC)OC.[BH4-].[Na+]>CO>[CH2:33]([N:27]([CH2:24][CH2:25][CH3:26])[CH2:28][CH2:29][CH2:30][CH2:31][N:15]1[CH2:16][CH2:17][CH:12]([CH2:11][NH:10][C:8](=[O:9])[N:7]([CH2:18][C:19]2[NH:20][CH:21]=[CH:22][N:23]=2)[CH2:6][C:2]2[NH:1][CH:5]=[CH:4][N:3]=2)[CH2:13][CH2:14]1)[CH2:34][CH3:35]

Participants

6

Reactant 4

HCID 9005Trimethyl orthoformateHCID 4311764Sodium borohydrideHCID 226111444-(Dipropylamino)butanalHCID 67502645N,N-bis(1H-imidazol-2-ylmethyl)-N'-(piperidin-4-ylmethyl)urea

Product 1

HCID 57764673N'-({1-[4-(dipropylamino)butyl]-4-piperidinyl}methyl)-N,N-bis(1H-imidazol-2-ylmethyl)ureaYield 34.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Under an argon atmosphere, to a methanol (2.3 mL) solution of the compound (73 mg) obtained in Example 10, 4-(dipropylamino)butanal (39 mg) and trimethyl orthoformate (49 mg) were added at 0° C. The reaction solution was stirred at room temperature for 2 hours. To the reaction solution, sodium borohydride (17 mg) was added at 0° C., followed by stirring for one hour. The reaction solution was concentrated under reduced pressure, and then an aqueous 5N sodium hydroxide solution (10 mL) was added to the residue. The aqueous layer was extracted twice with chloroform (30 mL). The combined organic layer was dried over anhydrous magnesium sulfate. After removing the anhydrous sodium sulfate by filtration, the filtrate was concentrated. The residue was purified by silica gel chromatography (dichrolomethane:methanol:28% aqueous ammonia=10:1:0→80:10:1) to obtain the title compound (37 mg) having the following physical properties.

Workup

  1. stirringby stirring for one hour
  2. concentrationThe reaction solution was concentrated under reduced pressure
  3. additionan aqueous 5N sodium hydroxide solution (10 mL) was added to the residue
  4. extractionThe aqueous layer was extracted twice with chloroform (30 mL)
  5. dry with materialThe combined organic layer was dried over anhydrous magnesium sulfate
  6. customAfter removing the anhydrous sodium sulfate
  7. filtrationby filtration
  8. concentrationthe filtrate was concentrated
  9. customThe residue was purified by silica gel chromatography (dichrolomethane:methanol:28% aqueous ammonia=10:1:0→80:10:1)

Sources & evidence

ORD record
ord-c15e52fb1123480191d9a81fc569952b
Source dataset
uspto-grants-2012_05
Patent number
US08168783B2

Reaction notes

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