HCID 89771889, compound → HCID 53482635, compound

HRID 404854Notes

Reaction equation

HRID 404854 reaction equation
[CH2:1]([C:8]1[O:12][C:11]([C:13]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=2[F:20])=[N:10][C:9]=1[C@H:21]([N:26]([CH2:32][C@H:33]1[C@@H:37]([F:38])[CH2:36][N:35](C(OCC2C=CC=CC=2)=O)[CH2:34]1)[C:27](=[O:31])[C@@H:28]([OH:30])[CH3:29])[C:22]([CH3:25])([CH3:24])[CH3:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C(O)C.[Pd]>[CH2:1]([C:8]1[O:12][C:11]([C:13]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=2[F:20])=[N:10][C:9]=1[C@H:21]([N:26]([CH2:32][C@H:33]1[C@@H:37]([F:38])[CH2:36][NH:35][CH2:34]1)[C:27](=[O:31])[C@@H:28]([OH:30])[CH3:29])[C:22]([CH3:25])([CH3:23])[CH3:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 1

HCID 89771889HCID 89771889, compound

Product 1

HCID 53482635HCID 53482635, compoundYield 590.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a solution of (3R,4R)-benzyl 3-(((S)-N-((R)-1-(5-benzyl-2-(2,5-difluorophenyl)oxazol-4-yl)-2,2-dimethylpropyl)-2-hydroxypropanamido)methyl)-4-fluoropyrrolidine-1-carboxylate (6.5 mg, 0.8 μmol) in degassed ethanol (980 μL, 0.01 M solution) was added Pd/C (5.0 mg) under anhydrous N2 atmosphere. After flushed with hydrogen gas, the reaction mixture equipped with a hydrogen gas balloon was stirred at room temperature for 30 min. The reaction mixture was filtered through Celite® pad that was washed with methanol and EtOAc. The volatile organic filtrate was removed in vacuo to give the crude amine, which was purified by preparative reverse phase HPLC. The combined fractions of the product were neutralized with saturated NaHCO3 solution, which was then extracted with EtOAc. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by preparative TLC to yield (S)-N-((R)-1-(5-benzyl-2-(2,5-difluorophenyl)oxazol-4-yl)-2,2-dimethylpropyl)-N-(((3S,4R)-4-fluoropyrrolidin-3-yl)methyl)-2-hydroxypropanamide (2.5 mg, 48.2%) as the free amine. LC/MS (uplc): MH+ 530.3, 0.94 min.

Workup

  1. customAfter flushed with hydrogen gas
  2. customthe reaction mixture equipped with a hydrogen gas balloon
  3. filtrationThe reaction mixture was filtered through Celite® pad that
  4. washwas washed with methanol and EtOAc
  5. customThe volatile organic filtrate was removed in vacuo
  6. customto give the crude amine, which
  7. customwas purified by preparative reverse phase HPLC
  8. extractionwas then extracted with EtOAc
  9. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe crude product was purified by preparative TLC

Sources & evidence

ORD record
ord-0962f73b5a184c72b68dfcd782b6e316
Source dataset
uspto-grants-2014_06
Patent number
US08748626B2

Reaction notes

Loading…