Hydrochloric Acid → N-(4-dipropylaminomethylbenzyl)-N'-(1H-imidazol-2-ylmethyl)-N-methyl-N'-(1-methyl-1H-imidazol-2-ylmethyl)-butane-1,4-diamine

HRID 348722Notes

Reaction equation

HRID 348722 reaction equation
Cl.[CH2:2]([N:5]([CH2:9][C:10]1[CH:35]=[CH:34][C:13]([CH2:14][NH:15][CH2:16][CH2:17][CH2:18][CH2:19][N:20]([CH2:28][C:29]2[NH:30][CH:31]=[CH:32][N:33]=2)[CH2:21][C:22]2[N:23]([CH3:27])[CH:24]=[CH:25][N:26]=2)=[CH:12][CH:11]=1)[CH2:6][CH2:7][CH3:8])[CH2:3][CH3:4].[CH:36](OC)(OC)OC.C=O.[BH4-].[Na+]>CO.C(N(CC)CC)C>[CH2:2]([N:5]([CH2:9][C:10]1[CH:11]=[CH:12][C:13]([CH2:14][N:15]([CH3:36])[CH2:16][CH2:17][CH2:18][CH2:19][N:20]([CH2:28][C:29]2[NH:33][CH:32]=[CH:31][N:30]=2)[CH2:21][C:22]2[N:23]([CH3:27])[CH:24]=[CH:25][N:26]=2)=[CH:34][CH:35]=1)[CH2:6][CH2:7][CH3:8])[CH2:3][CH3:4]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 9005Trimethyl orthoformateHCID 4311764Sodium borohydrideHCID 58801886N-(4-dipropylaminomethylbenzyl)-N'-(1H-imidazol-2-ylmethyl)-N'-(1-methyl-1H-imidazol-2-ylmethyl)-1,4-butanediamine

Product 1

HCID 58801927N-(4-dipropylaminomethylbenzyl)-N'-(1H-imidazol-2-ylmethyl)-N-methyl-N'-(1-methyl-1H-imidazol-2-ylmethyl)-butane-1,4-diamine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8471TriethylamineSolvent

Procedure

The hydrochloride (39.4 mg) of the compound obtained in Example 117-5 was dissolved in methanol (1.0 ml) and added with triethylamine (0.050 ml), trimethyl orthoformate (0.040 ml), and a 36% formaldehyde solution (0.020 ml), followed by stirring at room temperature for 2 hours. The solution was gradually added with sodium borohydride (15.0 mg) after having been cooled to 0° C., and then warmed to room temperature, followed by stirring for 1 hour. After completion of the reaction, the solvent was distilled off under reduced pressure. The residue was dissolved in chloroform and washed with a 1 mol/l sodium hydroxide aqueous solution, followed by extraction with chloroform. The organic layer was washed with saturated saline solution and dried with anhydrous sodium sulfate. After filtration, the solvent was distilled off under reduced pressure. Then, the residue was purified through silica gel column chromatography (chloroform/methanol) and treated with hydrochloric acid, thereby obtaining hydrochloride (28.2 mg) of the subject compound as a white solid.

Workup

  1. temperatureafter having been cooled to 0° C.
  2. temperaturewarmed to room temperature
  3. stirringby stirring for 1 hour
  4. customAfter completion of the reaction
  5. distillationthe solvent was distilled off under reduced pressure
  6. dissolutionThe residue was dissolved in chloroform
  7. washwashed with a 1 mol/l sodium hydroxide aqueous solution
  8. extractionfollowed by extraction with chloroform
  9. washThe organic layer was washed with saturated saline solution
  10. dry with materialdried with anhydrous sodium sulfate
  11. filtrationAfter filtration
  12. distillationthe solvent was distilled off under reduced pressure
  13. customThen, the residue was purified through silica gel column chromatography (chloroform/methanol)
  14. additiontreated with hydrochloric acid

Sources & evidence

ORD record
ord-0be61ce7d5d5437da7de0ebc84b33eff
Source dataset
uspto-grants-2007_02
Patent number
US07176227B2

Reaction notes

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