1-{[(S)-2-(3-Trifluoromethoxy-phenylcarbamoyl)-pyrrolidine-1-carbonyl]-amino}-indolizine-3-carboxylic acid benzyl ester → 1-{[(S)-2-(3-Trifluoromethoxy-phenylcarbamoyl)-pyrrolidine-1-carbonyl]-amino}-indolizine-3-carboxylic acid

HRID 1527545Notes

Reaction equation

HRID 1527545 reaction equation
C([O:8][C:9]([C:11]1[N:19]2[C:14]([CH:15]=[CH:16][CH:17]=[CH:18]2)=[C:13]([NH:20][C:21]([N:23]2[CH2:27][CH2:26][CH2:25][C@H:24]2[C:28](=[O:41])[NH:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([O:36][C:37]([F:40])([F:39])[F:38])[CH:31]=2)=[O:22])[CH:12]=1)=[O:10])C1C=CC=CC=1>C1COCC1.[Pd]>[F:40][C:37]([F:38])([F:39])[O:36][C:32]1[CH:31]=[C:30]([NH:29][C:28]([C@@H:24]2[CH2:25][CH2:26][CH2:27][N:23]2[C:21]([NH:20][C:13]2[CH:12]=[C:11]([C:9]([OH:10])=[O:8])[N:19]3[C:14]=2[CH:15]=[CH:16][CH:17]=[CH:18]3)=[O:22])=[O:41])[CH:35]=[CH:34][CH:33]=1

Participants

4

Reactant 1

HCID 682844901-{[(S)-2-(3-Trifluoromethoxy-phenylcarbamoyl)-pyrrolidine-1-carbonyl]-amino}-indolizine-3-carboxylic acid benzyl ester

Product 1

HCID 682836541-{[(S)-2-(3-Trifluoromethoxy-phenylcarbamoyl)-pyrrolidine-1-carbonyl]-amino}-indolizine-3-carboxylic acid

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To 1-{[(S)-2-(3-Trifluoromethoxy-phenylcarbamoyl)-pyrrolidine-1-carbonyl]-amino}-indolizine-3-carboxylic acid benzyl ester (100 mg, 0.177 mmol) dissolved in THF (3 mL) was added Pd/C 10% (20 mg). Air was removed from the flask under vacuum and replaced with nitrogen three times, finally nitrogen was removed and replaced with hydrogen and the mixture was stirred at RT for 5 h. Hydrogen was removed and replaced by nitrogen, the catalyst was removed by filtration through a pad of Celite and washed with THF. Solvents were concentrated to give a mixture containing the desired compound contaminated with 20% of the decarboxylated analog. The mixture was used without further purification in the next step. LC/MS: 475 [M−H]−; tR (HPLC conditions a): 3.41 min.

Workup

  1. customAir was removed from the flask under vacuum
  2. customwas removed
  3. customHydrogen was removed
  4. customthe catalyst was removed by filtration through a pad of Celite
  5. washwashed with THF
  6. concentrationSolvents were concentrated
  7. customto give a mixture

Sources & evidence

ORD record
ord-bfdc0ddf5555411e8038dbf4f4517772
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

Loading…