Trimethyl orthoformate → N-(4-dipropylamino-butyl)-4-{[(1-methyl-1H-imidazol-2-ylmethyl)-amino]-methyl}-benzamide

HRID 2080777Notes

Reaction equation

HRID 2080777 reaction equation
[NH2:1][CH2:2][C:3]1[CH:22]=[CH:21][C:6]([C:7]([NH:9][CH2:10][CH2:11][CH2:12][CH2:13][N:14]([CH2:18][CH2:19][CH3:20])[CH2:15][CH2:16][CH3:17])=[O:8])=[CH:5][CH:4]=1.C(OC)(OC)OC.[CH3:30][N:31]1[CH:35]=[CH:34][N:33]=[C:32]1[CH:36]=O.[BH4-].[Na+]>CO.O>[CH2:18]([N:14]([CH2:15][CH2:16][CH3:17])[CH2:13][CH2:12][CH2:11][CH2:10][NH:9][C:7](=[O:8])[C:6]1[CH:21]=[CH:22][C:3]([CH2:2][NH:1][CH2:36][C:32]2[N:31]([CH3:30])[CH:35]=[CH:34][N:33]=2)=[CH:4][CH:5]=1)[CH2:19][CH3:20]

Participants

7

Reactant 4

HCID 9005Trimethyl orthoformateHCID 1395751-Methyl-2-imidazolecarboxaldehydeHCID 4311764Sodium borohydrideHCID 231553934-(aminomethyl)-N-(4-{dipropylamino}butyl)benzamide

Product 1

HCID 67103805N-(4-dipropylamino-butyl)-4-{[(1-methyl-1H-imidazol-2-ylmethyl)-amino]-methyl}-benzamideYield 111.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent

Procedure

The compound (538 mg) obtained in Example 20-2 was dissolved in anhydrous methanol (10 ml), added with trimethyl orthoformate (600 μl) at room temperature under a nitrogen atmosphere, and then added with a methanol solution (2.0 ml) containing 1-methyl-2-imidazole carboxaldehyde (240 mg). The whole was stirred at room temperature for 36 hours and then added with sodium borohydride (140 mg) under ice-cooling. The whole was warmed to room temperature and stirred for 1 hour. After completion of the reaction, the resultant was added with water under ice-cooling while the whole was stirred. The solvent was distilled off under reduced pressure and the residue was dissolved in chloroform and added with water, followed by extraction of the aqueous layer with chloroform. The organic layer was washed with a saturated saline solution and dried with anhydrous sodium sulfate. After filtration, the solvent was distilled off under reduced pressure. The residue was purified through silica gel column chromatography (chloroform/methanol), thereby obtaining the subject compound (782 mg) as a yellow oily substance.

Workup

  1. temperaturecooling
  2. temperatureThe whole was warmed to room temperature
  3. stirringstirred for 1 hour
  4. customAfter completion of the reaction
  5. temperaturecooling while the whole
  6. stirringwas stirred
  7. distillationThe solvent was distilled off under reduced pressure
  8. dissolutionthe residue was dissolved in chloroform
  9. additionadded with water
  10. extractionfollowed by extraction of the aqueous layer with chloroform
  11. washThe organic layer was washed with a saturated saline solution
  12. dry with materialdried with anhydrous sodium sulfate
  13. filtrationAfter filtration
  14. distillationthe solvent was distilled off under reduced pressure
  15. customThe residue was purified through silica gel column chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-6f4aad7bcb074dd6b3b40d8c9ea577ce
Source dataset
uspto-grants-2011_04
Patent number
US07932281B2

Reaction notes

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