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Trimethyl orthoformate → 2-{[(1H-imidazol-2-ylmethyl)-(1-methyl-1H-imidazol-2-ylmethyl)-amino]-methyl}-6-(3-dipropylaminopropyl)-naphtalene

HRID 348741
Notes
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Reaction equation

HRID 348741 reaction equation
[NH2:1][CH2:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH2:13][CH2:14][CH2:15][N:16]([CH2:20][CH2:21][CH3:22])[CH2:17][CH2:18][CH3:19])[CH:9]=2)[CH:4]=1.C(OC)(OC)OC.[NH:30]1[CH:34]=[CH:33][N:32]=[C:31]1[CH:35]=O.[BH4-].[Na+].[Cl-].[NH4+].C([BH3-])#N.[Na+].[CH3:45][N:46]1[CH:50]=[CH:49][N:48]=[C:47]1[CH:51]=O>CO.C(O)(=O)C>[NH:30]1[CH:34]=[CH:33][N:32]=[C:31]1[CH2:35][N:1]([CH2:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH2:13][CH2:14][CH2:15][N:16]([CH2:20][CH2:21][CH3:22])[CH2:17][CH2:18][CH3:19])[CH:9]=2)[CH:4]=1)[CH2:51][C:47]1[N:46]([CH3:45])[CH:50]=[CH:49][N:48]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

10

Reactant 7

HCID 9005Trimethyl orthoformateHCID 249551H-imidazole-2-carbaldehydeHCID 25517Ammonium ChlorideHCID 1395751-Methyl-2-imidazolecarboxaldehydeHCID 4311764Sodium borohydrideHCID 5003444Sodium cyanoborohydride
HCID 23079216
2-Aminomethyl-6-(3-dipropylaminopropyl)naphthalene

Product 1

HCID 100277962-{[(1H-imidazol-2-ylmethyl)-(1-methyl-1H-imidazol-2-ylmethyl)-amino]-methyl}-6-(3-dipropylaminopropyl)-naphtalene

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent2×

Procedure

The compound (280 mg) obtained in Example 121-11 was dissolved in anhydrous methanol (5.0 ml) and added with trimethyl orthoformate (0.154 ml) and 2-imidazole carboxaldehyde (90.1 mg), followed by stirring at room temperature for 2 hours under a nitrogen atmosphere. Subsequently, the solution was added with sodium borohydride (53.3 mg) in an ice bath and stirred at room temperature for 30 minutes. After completion of the reaction, a saturated aqueous ammonium chloride solution was added to the solution, and the whole was stirred. The solution was subjected to extraction with chloroform. The extract was washed with a saturated aqueous sodium bicarbonate solution and saturated saline solution. Then, the organic layer was dried with anhydrous sodium sulfate. The residue obtained was dissolved in anhydrous methanol (10 ml) and added with sodium cyanoborohydride (93.6 mg), acetic acid (3.00 ml), and 1-methyl-2-imidazole carboxaldehyde (120 mg), followed by stirring at room temperature for 2 days under a nitrogen atmosphere. After completion of the reaction, the solvent was distilled off and the residue was then dissolved in chloroform. The solution was added with a saturated aqueous sodium bicarbonate solution and stirred. The solution was subjected to extraction with chloroform and the extract was then washed with a saturated aqueous sodium bicarbonate solution and saturated saline solution. The organic layer was dried with anhydrous sodium sulfate and then the solvent was distilled off. Subsequently, the residue was purified through silica gel column chromatography (chloroform/ethyl acetate) and treated with hydrochloric acid, thereby obtaining hydrochloride (318 mg) of the subject compound as a white solid.

Workup

  1. stirringstirred at room temperature for 30 minutes
  2. customAfter completion of the reaction
  3. stirringthe whole was stirred
  4. extractionThe solution was subjected to extraction with chloroform
  5. washThe extract was washed with a saturated aqueous sodium bicarbonate solution and saturated saline solution
  6. dry with materialThen, the organic layer was dried with anhydrous sodium sulfate
  7. customThe residue obtained
  8. stirringby stirring at room temperature for 2 days under a nitrogen atmosphere
  9. customAfter completion of the reaction
  10. distillationthe solvent was distilled off
  11. dissolutionthe residue was then dissolved in chloroform
  12. additionThe solution was added with a saturated aqueous sodium bicarbonate solution
  13. stirringstirred
  14. extractionThe solution was subjected to extraction with chloroform
  15. washthe extract was then washed with a saturated aqueous sodium bicarbonate solution and saturated saline solution
  16. dry with materialThe organic layer was dried with anhydrous sodium sulfate
  17. distillationthe solvent was distilled off
  18. customSubsequently, the residue was purified through silica gel column chromatography (chloroform/ethyl acetate)
  19. additiontreated with hydrochloric acid

Sources & evidence

ORD record
ord-a30154220d74418989f066f3c18a8d29
Source dataset
uspto-grants-2007_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07176227B2

Reaction notes

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