(S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-(4-fluorobenzylidene)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide → (2S,4S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-(4-fluorobenzyl)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide

HRID 1630292Notes

Reaction equation

HRID 1630292 reaction equation
[N:1]1([CH2:6][C:7]([N:9]2[CH2:13][C:12](=[CH:14][C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[CH2:11][C@H:10]2[C:22]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=3)=[CH:27][CH:26]=2)=[O:23])=[O:8])[CH:5]=[N:4][CH:3]=[N:2]1>[Pd].CO>[N:1]1([CH2:6][C:7]([N:9]2[CH2:13][C@@H:12]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[CH2:11][C@H:10]2[C:22]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][C:32]3[CH:33]=[CH:34][C:35]([F:38])=[CH:36][CH:37]=3)=[CH:27][CH:26]=2)=[O:23])=[O:8])[CH:5]=[N:4][CH:3]=[N:2]1

Participants

4

Reactant 1

HCID 67009559(S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-(4-fluorobenzylidene)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide

Product 1

HCID 45377580(2S,4S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-(4-fluorobenzyl)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamideYield 70.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

Step (c) A flask was charged with (S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-(4-fluorobenzylidene)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide (15 mg, 0.027 mmol), palladium on carbon (10%, 50 mg) and methanol (5 mL) and the mixture was placed under a hydrogen atmosphere (balloon). The mixture was stirred for 2 hours at ambient temperature and then concentrated. Product was purified from the residue by chromatography (EtOAc to EtOAc/MeOH (9:1)+1% NEt3) to give Compound 76, (2S,4S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-(4-fluorobenzyl)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide (10 mg, 0.019 mmol, 69%), as an off-white solid. 1H-NMR (400 MHz, CDCl3): 8.61 (s, 1H), 8.22 (s, 1H), 7.98 (s, 1H), 7.45 (d, J=10.0 Hz, 2H), 7.18-7.14 (m, 2H), 7.03-6.91 (m, 8H), 5.00 (m, 2H), 4.62 (m, 1H), 3.76 (dd, J=11.2, 7.6 Hz, 1H), 3.25 (m, 1H), 2.85 (dd, J=12.8, 7.6 Hz, 1H), 2.73 (dd, J=12.8, 7.6 Hz, 1H), 2.57 (m, 1H), 2.30 (m, 2H). MS (EI) for C28H25F2N5O3. found 518.2 (MH+).

Workup

  1. concentrationconcentrated
  2. customProduct was purified from the residue by chromatography (EtOAc to EtOAc/MeOH (9:1)+1% NEt3)

Sources & evidence

ORD record
ord-0d363268fc5a4d48b3f6330993902607
Source dataset
uspto-grants-2014_07
Patent number
US08791102B2

Reaction notes

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