benzyl (3R,5S)-1-(2-(1H-imidazol-5-yl)acetyl)-5-(4-(4-fluorophenoxy)phenylcarbamoyl)pyrrolidin-3-ylcarbamate → (2S,4R)-1-(2-(1H-imidazol-5-yl)acetyl)-4-amino-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide

HRID 1630286Notes

Reaction equation

HRID 1630286 reaction equation
[NH:1]1[C:5]([CH2:6][C:7]([N:9]2[C@H:13]([C:14](=[O:30])[NH:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]4[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=4)=[CH:18][CH:17]=3)[CH2:12][C@@H:11]([NH:31]C(=O)OCC3C=CC=CC=3)[CH2:10]2)=[O:8])=[CH:4][N:3]=[CH:2]1>[Pd].CO>[NH:1]1[C:5]([CH2:6][C:7]([N:9]2[CH2:10][C@H:11]([NH2:31])[CH2:12][C@H:13]2[C:14]([NH:15][C:16]2[CH:17]=[CH:18][C:19]([O:22][C:23]3[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=3)=[CH:20][CH:21]=2)=[O:30])=[O:8])=[CH:4][N:3]=[CH:2]1

Participants

4

Reactant 1

HCID 70641202benzyl (3R,5S)-1-(2-(1H-imidazol-5-yl)acetyl)-5-(4-(4-fluorophenoxy)phenylcarbamoyl)pyrrolidin-3-ylcarbamate

Product 1

HCID 67010250(2S,4R)-1-(2-(1H-imidazol-5-yl)acetyl)-4-amino-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamideYield 85.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A flask was charged with benzyl (3R,5S)-1-(2-(1H-imidazol-5-yl)acetyl)-5-(4-(4-fluorophenoxy)phenylcarbamoyl)pyrrolidin-3-ylcarbamate (800 mg, 1.43 mmol), prepared as in Example 1, palladium on carbon (10%, 80 mg) and methanol (30 mL) and the mixture was placed under a hydrogen atmosphere at 40 psi (parr shaker). The reaction was allowed to proceed for 4 hours and the mixture was filtered and concentrated. Product was purified from the residue by reverse phase HPLC to give (2S,4R)-1-(2-(1H-imidazol-5-yl)acetyl)-4-amino-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide (516 mg, 1.22 mmol, 85%) as an off-white solid.

Workup

  1. filtrationthe mixture was filtered
  2. concentrationconcentrated
  3. customProduct was purified from the residue by reverse phase HPLC

Sources & evidence

ORD record
ord-96de052761b043028948856de52c6dba
Source dataset
uspto-grants-2014_07
Patent number
US08791102B2

Reaction notes

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