2-(4-(4-((4-Nitrophenyl)sulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol → 2-[4-[4-(4-Aminophenylsulfonyl)piperazino]phenyl]-1,1,1,3,3,3-hexafluoro-2-propanol

HRID 1972481Notes

Reaction equation

HRID 1972481 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([N:13]2[CH2:18][CH2:17][N:16]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([OH:34])([C:30]([F:33])([F:32])[F:31])[C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=3)[CH2:15][CH2:14]2)(=[O:12])=[O:11])=[CH:6][CH:5]=1)([O-])=O>[Pd].CCO>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([S:10]([N:13]2[CH2:14][CH2:15][N:16]([C:19]3[CH:20]=[CH:21][C:22]([C:25]([OH:34])([C:26]([F:29])([F:28])[F:27])[C:30]([F:31])([F:32])[F:33])=[CH:23][CH:24]=3)[CH2:17][CH2:18]2)(=[O:11])=[O:12])=[CH:8][CH:9]=1

Participants

4

Reactant 1

HCID 866703612-(4-(4-((4-Nitrophenyl)sulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol

Product 1

HCID 763358992-[4-[4-(4-Aminophenylsulfonyl)piperazino]phenyl]-1,1,1,3,3,3-hexafluoro-2-propanolYield 53.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A 100-mL round-bottomed flask was charged with 2-(4-(4-((4-nitrophenyl)sulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (180 mg) and EtOH (20 mL). The reaction was placed under an atmosphere of argon. 10% Pd/C (37.3 mg, 0.351 mmol, Sigma-Aldrich, St. Louis, Mo.) was added and the reaction stirred under a balloon atmosphere of H2 (0.707 mg, 0.351 mmol) for 12 h. The reaction was carefully filtered through a pad of Celite®(diatomaceous earth), 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-aminophenyl)sulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (90 mg). 1H NMR (400 MHz, CD3OD) δ=7.54 (d, J=8.8 Hz, 2H), 7.48 (d, J=8.6 Hz, 2H), 6.98 (d, J=9.0 Hz, 2H), 6.73 (d, J=8.6 Hz, 2H), 3.31-3.26 (m, 4H), 3.11-3.03 (m, 4H). m/z (ESI, +ve ion) 484.1 (M+H)+. GK-GKRP IC50 (Binding)=0.582 μM; GK-GKRP EC50 (LC MS/MS-2)=0.828 μM.

Workup

  1. filtrationThe reaction was carefully filtered through a pad of Celite®(diatomaceous earth),
  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-c15ab2ff9f7447209eb51444e20296ee
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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