Hydrochloric Acid → HCID 58243855, compound

HRID 389149Notes

Reaction equation

HRID 389149 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:17][C:18]([CH3:36])([C:20]2[N:24]([CH3:25])[C:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[C:32]([F:35])([F:34])[F:33])=[N:22][N:21]=2)[CH3:19])=[C:6]([CH:16]=1)[C:7]([NH:9][CH2:10][C:11]([O:13]CC)=O)=[O:8].[CH:37]1([NH2:40])[CH2:39][CH2:38]1.C(=O)([O-])[O-].[K+].[K+].[OH-].[Na+].Cl>C(O)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:17][C:18]([CH3:36])([C:20]2[N:24]([CH3:25])[C:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[C:32]([F:34])([F:33])[F:35])=[N:22][N:21]=2)[CH3:19])=[C:6]([CH:16]=1)[C:7]([NH:9][CH2:10][C:11]([NH:40][CH:37]1[CH2:39][CH2:38]1)=[O:13])=[O:8]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 69828CyclopropylamineHCID 58243822HCID 58243822, compound

Product 1

HCID 58243855HCID 58243855, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

Ethyl N-[5-chloro-2-(1-methyl-1-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}ethoxy)benzoyl]glycinate (300 mg) was dissolved in ethanol (6 ml), and cyclopropylamine (0.395 ml) was added thereto, followed by stirring at room temperature for one hour. Potassium carbonate (240 mg) was added to the reaction solution, followed by stirring at 60° C. for 3 hours. Water and a 1M aqueous sodium hydroxide solution were added to the reaction solution, followed by stirring for 30 minutes, 1M hydrochloric acid was added thereto, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then concentrated. The resulting residue was dissolved in DMF (6 ml), WSC•monohydrochloride (220 mg), HOAt (156 mg) and cyclopropylamine (0.395 ml) were added thereto, followed by stirring at room temperature for one hour, and diisopropylamine (0.500 ml) was added thereto, followed by stirring for one hour. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with water, 1M aqueous sodium hydroxide solution and then saturated brine in this order, and concentrated under reduced pressure. The resulting solid was washed with diisopropylether to obtain, as a white solid, 5-chloro-N-[2-(cyclopropylamino)-2-oxoethyl]-2-(1-methyl-1-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}ethoxy)benzamide (142 mg).

Workup

  1. stirringby stirring at 60° C. for 3 hours
  2. stirringby stirring for 30 minutes
  3. extractionfollowed by extraction with ethyl acetate
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  5. concentrationconcentrated
  6. dissolutionThe resulting residue was dissolved in DMF (6 ml)
  7. additionWSC•monohydrochloride (220 mg), HOAt (156 mg) and cyclopropylamine (0.395 ml) were added
  8. stirringby stirring at room temperature for one hour
  9. additiondiisopropylamine (0.500 ml) was added
  10. stirringby stirring for one hour
  11. additionWater was added to the reaction solution
  12. extractionfollowed by extraction with ethyl acetate
  13. washThe organic layer was washed with water, 1M aqueous sodium hydroxide solution
  14. concentrationsaturated brine in this order, and concentrated under reduced pressure
  15. washThe resulting solid was washed with diisopropylether

Sources & evidence

ORD record
ord-7e55a122cb52409488cc296f2b9ed539
Source dataset
uspto-grants-2013_02
Patent number
US08377923B2

Reaction notes

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