Dichloromethane → HCID 10696321, compound

HRID 344316Notes

Reaction equation

HRID 344316 reaction equation
C(O[C:6]([NH:8][CH2:9][CH:10]1[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][NH2:21])[CH2:12][CH2:11]1)=[O:7])(C)(C)C.[C:22](=[O:25])([O-])[O-].[K+].[K+].[C:28](Cl)(=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.[CH2:37]([Cl:39])Cl>>[NH2:13][C:12]1[C:37]([Cl:39])=[CH:14][C:15]([C:6]([NH:8][CH2:9][CH:10]2[CH2:11][CH2:12][N:13]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][NH:21][C:28](=[O:35])[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:14][CH2:15]2)=[O:7])=[C:10]([O:25][CH3:22])[CH:11]=1

Participants

5

Reactant 4

HCID 6344Dichloromethane2×HCID 7412Benzoyl chlorideHCID 11430Potassium CarbonateHCID 54377830HCID 54377830, compound

Product 1

HCID 10696321HCID 10696321, compound

Procedure

5-(4-tert-Butoxycarbonylaminomethylpiperidin-1-yl)pentylamine (1.2 g) was dissolved in methylene chloride (20 ml) and potassium carbonate (1.66 g) was added. Then, a solution of benzoyl chloride (0.47 ml) in methylene chloride was dropwise added under ice-cooling. The mixture was stirred at room temperature for 1 hr, and the reaction mixture was concentrated under reduced pressure. The residue was dissolved in 4N hydrochloric acid-dioxane solution (30 ml) and the mixture was stood at room temperature for 30 min. The reaction mixture was concentrated under reduced pressure. Dimethylformamide (30 ml) was added to the residue and the mixture was neutralized with triethylamine (1.1 ml). 4-Amino-5-chloro-2-methoxybenzoic acid (0.81 g) and 1-hydroxybenzotriazole (0.60 g) were added, and the mixture was stirred at 0° C. for 20 min. Then, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.85 g) was added and the mixture was stirred at room temperature for 8 hr. The reaction mixture was concentrated under reduced pressure. Aqueous potassium carbonate solution was added to the residue and the mixture was extracted with ethyl acetate. The extract was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography to give 0.68 g of 4-amino-N-(1-(5-benzoylaminopentyl)piperidin-4-ylmethyl)-5-chloro-2-methoxybenzamide.

Workup

  1. temperaturecooling
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in 4N hydrochloric acid-dioxane solution (30 ml)
  4. waitthe mixture was stood at room temperature for 30 min
  5. concentrationThe reaction mixture was concentrated under reduced pressure
  6. additionDimethylformamide (30 ml) was added to the residue
  7. addition4-Amino-5-chloro-2-methoxybenzoic acid (0.81 g) and 1-hydroxybenzotriazole (0.60 g) were added
  8. stirringthe mixture was stirred at 0° C. for 20 min
  9. additionThen, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.85 g) was added
  10. stirringthe mixture was stirred at room temperature for 8 hr
  11. concentrationThe reaction mixture was concentrated under reduced pressure
  12. additionAqueous potassium carbonate solution was added to the residue
  13. extractionthe mixture was extracted with ethyl acetate
  14. dry with materialThe extract was dried over magnesium sulfate
  15. concentrationconcentrated under reduced pressure
  16. customThe obtained residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-26a7bb58510944739716d34dc280d03c
Source dataset
uspto-grants-1999_01
Patent number
US05864039

Reaction notes

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