Triethylamine → HCID 178434720, compound

HRID 2391102Notes

Reaction equation

HRID 2391102 reaction equation
[C:1]1([C@H:7]([O:9][C:10](=[O:37])[NH:11][C:12]2[C:13]([CH3:36])=[N:14][O:15][C:16]=2[C:17]2[CH:22]=[CH:21][C:20]([C:23]3[CH:28]=[CH:27][C:26]([C:29]4([C:32](=[NH:35])[NH:33][OH:34])[CH2:31][CH2:30]4)=[CH:25][CH:24]=3)=[CH:19][CH:18]=2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.Cl[C:46](OCC)=[O:47]>C(Cl)Cl>[C:1]1([C@H:7]([O:9][C:10](=[O:37])[NH:11][C:12]2[C:13]([CH3:36])=[N:14][O:15][C:16]=2[C:17]2[CH:22]=[CH:21][C:20]([C:23]3[CH:28]=[CH:27][C:26]([C:29]4([C:32]5[NH:33][O:34][C:46](=[O:47])[N:35]=5)[CH2:30][CH2:31]4)=[CH:25][CH:24]=3)=[CH:19][CH:18]=2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 8471Triethylamine3×HCID 10928Ethyl chloroformateHCID 178434722HCID 178434722, compound

Product 1

HCID 178434720HCID 178434720, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To (5-{4′-[1-(N-hydroxycarbamimidoyl)-cyclopropyl]-biphenyl-4-yl}-3-methyl-isoxazol-4-yl)-carbamic acid (R)-1-phenyl-ethyl ester (0.66 mmol) in CH2Cl2 (5 mL) was added triethylamine (0.19 mL, 1.32 mmol) and ethyl chloroformate (0.127 mL, 1.32 mmol), and the reaction was stirred overnight at room temperature. Additional triethylamine (0.19 mL, 1.32 mmol) was added, and the reaction was stirred for 6 hours. Additional triethylamine (0.19 mL, 1.32 mmol) was added, and the reaction was stirred until complete. The mixture was diluted with CH2Cl2 (20 mL) and washed with 10% aqueous citric acid, and then dried over MgSO4, filtered, and concentrated. The residue was dissolved in toluene (10 mL), and the solution was refluxed for 3 days. After concentrating, the crude material was purified by silica gel chromatography (0-100% EtOAc in hexanes) to give the title compound.

Workup

  1. stirringthe reaction was stirred for 6 hours
  2. stirringthe reaction was stirred until complete
  3. washwashed with 10% aqueous citric acid
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in toluene (10 mL)
  8. temperaturethe solution was refluxed for 3 days
  9. concentrationAfter concentrating
  10. customthe crude material was purified by silica gel chromatography (0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-546ace8faf054b22915490f44e8b5c72
Source dataset
uspto-grants-2012_09
Patent number
US08273780B2

Reaction notes

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