Hydrochloric Acid → HCID 18536740, compound

HRID 412072Notes

Reaction equation

HRID 412072 reaction equation
C([C:3]1[CH:7]=[CH:6][N:5]([C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][C:17]=2[C:18]([F:21])([F:20])[F:19])[NH:14][C:13](=[O:22])[C:12]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:11]3)[CH:4]=1)=O.Cl.NO.C([O-])(=O)C.[Na+].Cl.[N:37]([C:40]1[CH:50]=[CH:49][C:43]([C:44]([O:46][CH2:47][CH3:48])=[O:45])=[CH:42][CH:41]=1)=[C:38]=[O:39].[CH2:51]([N:53](CC)CC)C>C(O)C.[C].[Pd].O.CN(C=O)C>[CH2:47]([O:46][C:44]([C:43]1[CH:49]=[CH:50][C:40]([NH:37][C:38]([NH:53][CH2:51][C:3]2[CH:7]=[CH:6][N:5]([C:8]3[CH:9]=[C:10]4[C:15](=[CH:16][C:17]=3[C:18]([F:20])([F:19])[F:21])[NH:14][C:13](=[O:22])[C:12]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:11]4)[CH:4]=2)=[O:39])=[CH:41][CH:42]=1)=[O:45])[CH3:48]

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium AcetateHCID 589805Ethyl 4-isocyanatobenzoateHCID 9951683HCID 9951683, compound

Product 1

HCID 18536740HCID 18536740, compoundYield 60.1%

Reagents, catalysts & solvents 4

HCID 178418390HCID 178418390, compoundCatalystHCID 702EthanolSolvent2×HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of the compound of Example 20 (25.6 mg, 67.7 μmol) in ethanol (2 ml) were added hydroxylamine hydrochloride (9.38 mg, 135 μmol) and successively sodium acetate (11.1 mg, 135 μmol), and the mixture was refluxed for 3 hours. After cooling, the insolubles were filtered off and solvent was distilled off. The residue obtained was dissolved into ethanol (6 ml) and then 10% palladium-carbon (3.00 mg) and successively concentrated hydrochloric acid (0.2 ml) were added, which was stirred for 2 hours at room temperature under hydrogen atmosphere (4 atm, 392 KPa). Catalyst was filtered off using celite and solvent was distilled off. After the residue obtained was dissolved into N,N-dimethylformaldehyde (2 ml), ethyl 4-isocyanatobenzoate (15.5 mg, 81.2 μmol) and successively triethylamine (14.2 μl, 102 μmol) were added and the mixture was stirred for 1 hour at 60° C. Water was added to the residue obtained by distilling off solvent, which was extracted with ethyl acetate. After dried the extract over anhydrous sodium sulfate, solvent was distilled off. A small quantity of ethyl acetate was added to the residue obtained. The crystals were collected by filtration, washed with ethyl acetate, and then air-dried, thereby obtaining 23.2 mg of title compound as greenish yellow powder. Yield 60%.

Workup

  1. temperaturethe mixture was refluxed for 3 hours
  2. temperatureAfter cooling
  3. filtrationthe insolubles were filtered off
  4. distillationsolvent was distilled off
  5. customThe residue obtained
  6. filtrationCatalyst was filtered off
  7. distillationwas distilled off
  8. customAfter the residue obtained
  9. additionwere added
  10. stirringthe mixture was stirred for 1 hour at 60° C
  11. customobtained
  12. distillationby distilling off solvent, which
  13. extractionwas extracted with ethyl acetate
  14. customAfter dried the
  15. extractionextract over anhydrous sodium sulfate, solvent
  16. distillationwas distilled off
  17. additionA small quantity of ethyl acetate was added to the residue
  18. customobtained
  19. filtrationThe crystals were collected by filtration
  20. washwashed with ethyl acetate
  21. customair-dried

Sources & evidence

ORD record
ord-ebe8e8cda6a4440e89d1abf8a0b386d3
Source dataset
uspto-grants-2003_05
Patent number
US06562839B1

Reaction notes

Loading…