2-(4-(4-((3-Fluoro-4-nitrophenyl)sulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol → 2-(4-(4-((4-Amino-3-fluorophenyl)sulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol

HRID 1972483Notes

Reaction equation

HRID 1972483 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([S:11]([N:14]2[CH2:19][CH2:18][N:17]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([OH:35])([C:31]([F:34])([F:33])[F:32])[C:27]([F:30])([F:29])[F:28])=[CH:22][CH:21]=3)[CH2:16][CH2:15]2)(=[O:13])=[O:12])[CH:5]=[CH:6][C:7]=1[N+:8]([O-])=O>[Pd].CCO>[NH2:8][C:7]1[CH:6]=[CH:5][C:4]([S:11]([N:14]2[CH2:15][CH2:16][N:17]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([OH:35])([C:27]([F:30])([F:28])[F:29])[C:31]([F:32])([F:33])[F:34])=[CH:22][CH:21]=3)[CH2:18][CH2:19]2)(=[O:12])=[O:13])=[CH:3][C:2]=1[F:1]

Participants

4

Reactant 1

HCID 866703622-(4-(4-((3-Fluoro-4-nitrophenyl)sulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol

Product 1

HCID 866703632-(4-(4-((4-Amino-3-fluorophenyl)sulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanolYield 18.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A 100-mL round-bottomed flask was charged 2-(4-(4-((3-fluoro-4-nitrophenyl)sulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (350 mg, 0.66 mmol) and EtOH (40 mL). The reaction was placed under an atmosphere of argon. 10% Pd/C (70.1 mg, 0.66 mmol) was added and the reaction was stirred under a balloon atmosphere of H2 for 12 h. The reaction was carefully filtered through a pad of Celite, rinsing with EtOH. The crude material was concentrated onto silica gel and purified via column chromatography (40 g silica gel, 0 to 10% MeOH in CH2Cl2) to give 2-(4-(4-((4-amino-3-fluorophenyl)sulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (60 mg). 1H NMR (400 MHz, CD3OD) δ=7.54 (d, J=8.6 Hz, 2H), 7.40-7.31 (m, 2H), 7.01-6.95 (m, 2H), 6.94-6.86 (m, 1H), 3.31-3.26 (m, 4H), 3.14-3.00 (m, 4H). m/z (ESI, +ve ion) 502.0 (M+H)+. GK-GKRP IC50 (Binding)=0.999 μM; GK-GKRP EC50 (LC MS/MS-2)=0.642 μM.

Workup

  1. filtrationThe reaction was carefully filtered through a pad of Celite
  2. washrinsing with EtOH
  3. concentrationThe crude material was concentrated onto silica gel
  4. custompurified via column chromatography (40 g silica gel, 0 to 10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-a7ea46b423304fb7827f76302dd9b7bb
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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