Dimethyl Sulfoxide → (S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-N-(4-(4-fluorophenoxy)phenyl)-4-oxopyrrolidine-2-carboxamide

HRID 1630290Notes

Reaction equation

HRID 1630290 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[N:11]1([CH2:16][C:17]([N:19]2[CH2:23][C@H:22]([OH:24])[CH2:21][C@H:20]2[C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=3)=[CH:30][CH:29]=2)=[O:26])=[O:18])[CH:15]=[N:14][CH:13]=[N:12]1.C(N(CC)CC)C.[Cl-].[NH4+]>C(Cl)Cl>[N:11]1([CH2:16][C:17]([N:19]2[CH2:23][C:22](=[O:24])[CH2:21][C@H:20]2[C:25]([NH:27][C:28]2[CH:29]=[CH:30][C:31]([O:34][C:35]3[CH:36]=[CH:37][C:38]([F:41])=[CH:39][CH:40]=3)=[CH:32][CH:33]=2)=[O:26])=[O:18])[CH:15]=[N:14][CH:13]=[N:12]1

Participants

7

Reactant 5

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 65578Oxalyl chlorideHCID 56953686(2S,4R)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-N-(4-(4-fluorophenoxy)phenyl)-4-hydroxypyrrolidine-2-carboxamide

Product 1

HCID 56954158(S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-N-(4-(4-fluorophenoxy)phenyl)-4-oxopyrrolidine-2-carboxamideYield 53.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

DMSO (3.78 mmol, 0.268 mL) was added drop-wise to a flask charged with oxalyl chloride (0.165 mL, 1.89 mmol) and methylene chloride (4 mL) at −78° C. The mixture was stirred for 15 minutes and then (2S,4R)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-N-(4-(4-fluorophenoxy)phenyl)-4-hydroxypyrrolidine-2-carboxamide (0.20 g, 0.47 mmol), prepared as in Reference 11, in methylene chloride (1 mL) was added via syringe. The reaction mixture then was stirred at 0° C. for 30 minutes and then quenched with triethylamine (2.0 mL, 15 mmol). The mixture was stirred for an additional 5 minutes and then saturated ammonium chloride (aq., 20 mL) was added. Product was purified from the organic layer by chromatography (EtOAc to EtOAc/MeOH (9:1)+1% NEt3) to give (S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-N-(4-(4-fluorophenoxy)phenyl)-4-oxopyrrolidine-2-carboxamide (0.11 g, 0.25 mmol, 53% yield) as an oil.

Workup

  1. stirringThe reaction mixture then was stirred at 0° C. for 30 minutes
  2. stirringThe mixture was stirred for an additional 5 minutes
  3. customProduct was purified from the organic layer by chromatography (EtOAc to EtOAc/MeOH (9:1)+1% NEt3)

Sources & evidence

ORD record
ord-22028e5b128b49fa96c46681a4391cb9
Source dataset
uspto-grants-2014_07
Patent number
US08791102B2

Reaction notes

Loading…