Ammonium formate → HCID 67342806, compound

HRID 1907151Notes

Reaction equation

HRID 1907151 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:20]([NH:22][C@@H:23]([C:25]([NH:27][CH2:28][C@@H:29]([NH:37]C(OCC1C=CC=CC=1)=O)[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:26])[CH3:24])=[O:21])[CH2:10][C:11]1[C:16]([CH3:17])=[CH:15][C:14]([OH:18])=[CH:13][C:12]=1[CH3:19])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])=O.[NH4+]>CO.[OH-].[Pd+2].[OH-]>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:20]([NH:22][C@@H:23]([C:25]([NH:27][CH2:28][C@@H:29]([NH2:37])[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:26])[CH3:24])=[O:21])[CH2:10][C:11]1[C:16]([CH3:17])=[CH:15][C:14]([OH:18])=[CH:13][C:12]=1[CH3:19])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 67340067HCID 67340067, compound

Product 1

HCID 67342806HCID 67342806, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of N-(tert-butoxycarbonyl)-2,6-dimethyl-L-tyrosyl-N-[(2S)-2-{[(benzyloxy)carbonyl]amino}-3-phenylpropyl]-D-alaninamide (450 mg, 0.70 mmol) from preparation 2 in methanol (10 mL) was added palladium hydroxide (40 mg) and ammonium formate (231 mg, 3.48 mmol) at room temperature. The reaction was then heated at 60° C. for 3 hours, after this time the reaction was allowed to cool and then filtered through a pad of Arbocel. The filtrate was concentrated under reduced pressure, the residue dissolved in methanol (5 mL) and loaded onto a 20 g SCX2 cartridge (pre-wetted with methanol). The cartridge was eluted with methanol to remove non-basic impurities and then eluted with 3M NH3 in methanol. Fractions containing the title compound were combined and concentrated under reduced pressure to afford the title compound as a white amorphous solid in 95% yield, 338 mg. 1H NMR (400 MHz, MeOH-d4) δ : 1.09 (d, 3H), 1.36 (s, 9H), 2.23 (s, 6H), 2.51-2.61 (m, 1H), 2.72-2.89 (m, 2H), 3.01-3.28 (m, 4H), 3.96-4.06 (m, 1H), 4.14-4.28 (m, 2H), 6.46 (s, 2H), 7.11-7.35 (m, 5H).

Workup

  1. temperatureto cool
  2. filtrationfiltered through a pad of Arbocel
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. dissolutionthe residue dissolved in methanol (5 mL)
  5. washThe cartridge was eluted with methanol
  6. customto remove non-basic impurities
  7. washeluted with 3M NH3 in methanol
  8. additionFractions containing the title compound
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e9301ab06ef9457d8cc0a249abbfa29d
Source dataset
uspto-grants-2013_12
Patent number
US08598123B2

Reaction notes

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