Acetic Acid → HCID 10745412, compound

HRID 361751Notes

Reaction equation

HRID 361751 reaction equation
C(OC(=O)C[CH:11]1[CH2:16][CH2:15][N:14]([C:17](=[O:37])[C:18]([CH3:36])([CH3:35])[CH:19]([CH2:31][CH2:32][CH2:33][CH3:34])[NH:20][C:21](=[O:30])[C:22]2[CH:27]=[CH:26][C:25]([C:28]#[N:29])=[CH:24][CH:23]=2)[CH2:13][CH2:12]1)C1C=CC=CC=1.C([N:41](CC)CC)C.S.[H][H].[C:49]([OH:52])(=[O:51])[CH3:50]>N1C=CC=CC=1.CO.[OH-].[Pd+2].[OH-]>[C:28]([C:25]1[CH:26]=[CH:27][C:22]([C:21]([NH:20][CH:19]([CH2:31][CH2:32][CH2:33][CH3:34])[C:18]([CH3:35])([CH3:36])[C:17]([N:14]2[CH2:15][CH2:16][CH:11]([CH2:50][C:49]([OH:52])=[O:51])[CH2:12][CH2:13]2)=[O:37])=[O:30])=[CH:23][CH:24]=1)(=[NH:29])[NH2:41]

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 402Hydrogen SulfideHCID 8471TriethylamineHCID 10506078HCID 10506078, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 10745412HCID 10745412, compoundYield 24.3%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolventHCID 1049PyridineSolvent

Procedure

N-4-Cyanobenzoyl-β-n-butyl-α,α-dimethyl-β-alanyl-4-piperidineacetic acid benzyl ester (106 mg, 0.20 mmol) was dissolved in pyridine (10 ml). To the resulting solution was added triethylamine (1 ml) and the mixture was saturated with hydrogen sulfide gas. The reaction vessel was sealed and the reaction mixture was stirred at room temperature overnight. The pyridine was distilled off and the volatile products were removed by two cycles of toluene azeotropy. The residue was dissolved in acetone (15 ml) and methyl iodide (1 ml) was added thereto, followed by refluxing for 30 minutes. The solvent was distilled off and the residue was dissolved in methanol (10 ml). To the obtained solution was added ammonium acetate (100 mg) and the mixture was refluxed for 2 hours. After the solvent was distilled off, the residue was dissolved in chloroform, washed with a saturated aqueous solution of NaCl and dried over anhydrous sodium sulfate. The obtained crude N-4-amidinobenzoyl-β-n-butyl-α,α-dimethyl-β-alanyl-4-piperidineacetic acid benzyl ester (32 mg, 0.06 mmol) was dissolved in an 50% aqueous methanol solution (10 ml) containing 5% acetic acid. To the resulting solution was added palladium hydroxide (50 mg) and the mixture was stirred in a hydrogen atmosphere for 15 minutes. The solvents were distilled off and the residue was dissolved in a 1N aqueous solution of acetic acid. The resulting solution was purified with a HPLC to yield N-(N-4-amidinobenzoyl-β-n-butyl-α,α-dimethyl-β-alanyl)-4-piperidineacetic acid (6.5 mg, 24.3%).

Workup

  1. customThe reaction vessel was sealed
  2. distillationThe pyridine was distilled off
  3. customthe volatile products were removed by two cycles of toluene azeotropy
  4. dissolutionThe residue was dissolved in acetone (15 ml)
  5. additionmethyl iodide (1 ml) was added
  6. temperatureby refluxing for 30 minutes
  7. distillationThe solvent was distilled off
  8. dissolutionthe residue was dissolved in methanol (10 ml)
  9. additionTo the obtained solution was added ammonium acetate (100 mg)
  10. temperaturethe mixture was refluxed for 2 hours
  11. distillationAfter the solvent was distilled off
  12. dissolutionthe residue was dissolved in chloroform
  13. washwashed with a saturated aqueous solution of NaCl
  14. dry with materialdried over anhydrous sodium sulfate
  15. customThe obtained crude N-4-amidinobenzoyl-β-n-butyl-α,α-dimethyl-β-alanyl-4-piperidineacetic acid benzyl ester (32 mg, 0.06 mmol)
  16. distillationThe solvents were distilled off
  17. dissolutionthe residue was dissolved in a 1N aqueous solution of acetic acid
  18. customThe resulting solution was purified with a HPLC

Sources & evidence

ORD record
ord-e83ec8c6f6c54f25a2462422e394da49
Source dataset
uspto-grants-1999_02
Patent number
US05866592

Reaction notes

Loading…