Water → HCID 58355136, compound

HRID 1509613Notes

Reaction equation

HRID 1509613 reaction equation
C(OC([N:8]1[CH2:13][C@@H:12]([N:14]([C:19]([C:21]2[N:22]=[N:23][N:24]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[C:25]=2[CH2:26][CH2:27][CH2:28][CH2:29][O:30][CH3:31])=[O:20])[CH2:15][CH:16]([CH3:18])[CH3:17])[CH2:11][C@@H:10]([C:38]([OH:40])=O)[CH2:9]1)=O)(C)(C)C.[CH3:41][C:42]1NN=[N:44][N:43]=1.C1(N=C=NC2CCCCC2)CCCCC1.O>C1(C)C=CC=CC=1>[CH3:31][O:30][CH2:29][CH2:28][CH2:27][CH2:26][C:25]1[N:24]([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[N:23]=[N:22][C:21]=1[C:19]([N:14]([C@H:12]1[CH2:11][C@@H:10]([C:38]2[O:40][C:42]([CH3:41])=[N:43][N:44]=2)[CH2:9][NH:8][CH2:13]1)[CH2:15][CH:16]([CH3:17])[CH3:18])=[O:20]

Participants

6

Reactant 4

HCID 962WaterHCID 10868DicyclohexylcarbodiimideHCID 58355160HCID 58355160, compoundHCID 178434708HCID 178434708, compound

Product 1

HCID 58355136HCID 58355136, compoundYield 47.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

(3R,5S)-1-(tert-Butoxycarbonyl)-5-[{[5-(4-methoxybutyl)-1-phenyl-1H-1,2,3-triazol-4-yl]carbonyl}(2-methylpropyl)amino]piperidine-3-carboxylic acid (200 mg) was dissolved in toluene (5 ml), 5-methyl-1H-tetrazole (36 mg) and N,N′-dicyclohexylcarbodiimide (96 mg) were added and the mixture was stirred at 80° C. for 15 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (1:3-1:1) was concentrated under reduced pressure. The residue was dissolved in toluene (1 ml), trifluoroacetic acid (1 ml) was added and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, basified with saturated aqueous sodium hydrogen carbonate, and the mixture was extracted twice with ethyl acetate. The extract was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was dissolved in methanol (1 ml), fumaric acid (12 mg) was added and the mixture was concentrated under reduced pressure to give the object product (85 mg).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. washa fraction eluted with ethyl acetate-hexane (1:3-1:1)
  6. concentrationwas concentrated under reduced pressure
  7. dissolutionThe residue was dissolved in toluene (1 ml)
  8. additiontrifluoroacetic acid (1 ml) was added
  9. stirringthe mixture was stirred at room temperature for 1 hr
  10. concentrationThe reaction mixture was concentrated under reduced pressure
  11. extractionthe mixture was extracted twice with ethyl acetate
  12. dry with materialThe extract was dried over anhydrous sodium sulfate
  13. customthe solvent was evaporated under reduced pressure
  14. dissolutionThe residue was dissolved in methanol (1 ml)
  15. additionfumaric acid (12 mg) was added
  16. concentrationthe mixture was concentrated under reduced pressure

Sources & evidence

ORD record
ord-f28525db7e11471b81a0e7ebd470d0c6
Source dataset
uspto-grants-2015_12
Patent number
US09221836B2

Reaction notes

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