Ammonium formate → HCID 57815105, compound

HRID 1160469Notes

Reaction equation

HRID 1160469 reaction equation
[NH2:1][C:2]1[N:3](C(OCC2C=CC=CC=2)=O)[CH:4]=[C:5]([CH2:7][CH2:8][O:9][CH3:10])[N:6]=1.[OH:21][C@H:22]([C@@H:26]([NH:34][C:35](=[O:59])[C:36]1[CH:41]=[C:40]([C:42]([NH:44][C@@H:45]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[CH3:46])=[O:43])[CH:39]=[C:38]([N:53]([CH3:58])[S:54]([CH3:57])(=[O:56])=[O:55])[CH:37]=1)[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:23](O)=[O:24].C1C=CC2N(O)N=NC=2C=1.O.CCN=C=NCCCN(C)C.Cl.C([O-])=O.[NH4+]>CN(C=O)C.CO.[Pd]>[CH2:27]([C@H:26]([NH:34][C:35](=[O:59])[C:36]1[CH:37]=[C:38]([N:53]([CH3:58])[S:54]([CH3:57])(=[O:56])=[O:55])[CH:39]=[C:40]([C:42]([NH:44][C@@H:45]([C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH3:46])=[O:43])[CH:41]=1)[C@@H:22]([OH:21])[C:23]([NH:1][C:2]1[NH:6][C:5]([CH2:7][CH2:8][O:9][CH3:10])=[CH:4][N:3]=1)=[O:24])[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

Participants

9

Reactant 5

HCID 2723923Ammonium formateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 57815115HCID 57815115, compoundHCID 68645827HCID 68645827, compound

Product 1

HCID 57815105HCID 57815105, compoundYield 67%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a 0.5 ml solution of benzyl 2-amino-4-(2-methoxyethyl)-1H-imidazole-1-carboxylate prepared in a similar manner to Example 32 63 mg (0.22 mmol), (2R,3S)-2-hydroxy-3-{[3-[methyl(methylsulfonyl)amino]-5-({[(1R)-1-phenylethyl]amino}carbonyl)benzoyl]amino}-4-phenylbutanoic acid obtained in Reference Example 39 63 mg (0.11 mmol) and HOBt —H2O 18 mg (0.12 mmol) in DMF was added EDC.HCl 23 mg (0.12 mmol) under ice-cooling and the mixture was heated to room temperature and stirred for 2 hours. The reaction solution then was extracted by adding ethyl acetate and 5% aqueous sodium carbonate solution. The organic layer was washed with an aqueous saturated sodium chloride solution and dried on sodium sulfate. Filtration and concentration gave a residue and the resulting residue was redissolved in methanol 2 ml and thereto were added ammonium formate 126 mg (2.00 mmol) and 10% Pd/C (containing 50%) 50 mg and the mixture was heated under reflux for 1.5 hours. The mixture was filtered to remove 10% Pd/C and concentrated. The concentrated residue was suspended in ethyl acetate and the mixture was washed with 5% sodium carbonate and an aqueous saturated sodium chloride solution. The organic layer was dried on sodium sulfate. After filtration and concentration of the mixture, the mixture was purified by a column chromatography on silica gel (eluted with a mixed solvent of chloroform and methanol) to give 50 mg (0.07 mmol) of the title compound (yield: 67%).

Workup

  1. temperaturecooling
  2. extractionThe reaction solution then was extracted
  3. additionby adding ethyl acetate and 5% aqueous sodium carbonate solution
  4. washThe organic layer was washed with an aqueous saturated sodium chloride solution
  5. customdried on sodium sulfate
  6. filtrationFiltration and concentration
  7. customgave a residue
  8. temperaturethe mixture was heated
  9. temperatureunder reflux for 1.5 hours
  10. filtrationThe mixture was filtered
  11. customto remove 10% Pd/C
  12. concentrationconcentrated
  13. washthe mixture was washed with 5% sodium carbonate
  14. customThe organic layer was dried on sodium sulfate
  15. filtrationAfter filtration and concentration of the mixture
  16. customthe mixture was purified by a column chromatography on silica gel (
  17. washeluted with a mixed solvent of chloroform and methanol)

Sources & evidence

ORD record
ord-290917a923f649e3bd00b9bea088ff52
Source dataset
uspto-grants-2010_10
Patent number
US07816387B2

Reaction notes

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