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

HRID 348597Notes

Reaction equation

HRID 348597 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH2:6][N:7]([CH2:14][C:15]1[CH:28]=[CH:27][C:18]([C:19]([NH:21][CH2:22][CH2:23][CH2:24][CH2:25][NH2:26])=[O:20])=[CH:17][CH:16]=1)[CH2:8][C:9]1[NH:10][CH:11]=[CH:12][N:13]=1.C(OC)(OC)OC.[C:36]1(=O)[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1.C([BH3-])#N.[Na+]>CO.C(O)(=O)C>[NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH2:6][N:7]([CH2:14][C:15]1[CH:28]=[CH:27][C:18]([C:19]([NH:21][CH2:22][CH2:23][CH2:24][CH2:25][NH:26][CH:36]2[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)=[O:20])=[CH:17][CH:16]=1)[CH2:8][C:9]1[NH:13][CH:12]=[CH:11][N:10]=1

Participants

7

Reactant 4

HCID 9005Trimethyl orthoformateHCID 10400CycloheptanoneHCID 5003444Sodium cyanoborohydrideHCID 103177174-{[bis(1H-imidazol-2-ylmethyl)-amino]-methyl}-N-(4-aminobutyl)-benzamide

Product 1

HCID 99824854-{[bis(1H-imidazol-2-ylmethyl)-amino]-methyl}-N-(4-cycloheptylaminobutyl)-benzamide

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

The compound (30.0 mg) obtained in Example 3-2 was dissolved in methanol (0.6 ml). This solution was added with trimethyl orthoformate (30.0 μl), acetic acid (30.0 μl), cycloheptanone (manufactured by Merck, Inc.) (18.7 μl), and sodium cyanoborohydride (14.9 mg), followed by stirring for 3 hours at room temperature. After completion of the reaction, the solvent was distilled off under reduced pressure. Then, the residue was dissolved in chloroform, washed with a 1 mol/l sodium hydroxide aqueous solution, and added with 1 mol/l hydrochloric acid to transfer the objective substance to the aqueous layer, followed by washing with chloroform. The 1 mol/l sodium hydroxide aqueous solution was added again to alkalinize the solution. The solution was subjected to extraction with chloroform and the extract was then 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 dried under vacuum and treated with hydrochloric acid, thereby obtaining hydrochloride (32.2 mg) of the subject compound as a white solid.

Workup

  1. customAfter completion of the reaction
  2. distillationthe solvent was distilled off under reduced pressure
  3. dissolutionThen, the residue was dissolved in chloroform
  4. washwashed with a 1 mol/l sodium hydroxide aqueous solution
  5. additionadded with 1 mol/l hydrochloric acid
  6. washby washing with chloroform
  7. additionThe 1 mol/l sodium hydroxide aqueous solution was added again
  8. extractionThe solution was subjected to extraction with chloroform
  9. washthe extract was then 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 dried under vacuum
  14. additiontreated with hydrochloric acid

Sources & evidence

ORD record
ord-ae9784c1b4f84acbb4b20650139901c8
Source dataset
uspto-grants-2007_02
Patent number
US07176227B2

Reaction notes

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