Triethylamine → 1,1,1,3,3,3-Hexafluoro-2-(4-(4-(3-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol

HRID 1972346Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1972346
[F:1][C:2]([F:22])([F:21])[C:3]([C:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)=[CH:11][CH:10]=1)([OH:8])[C:4]([F:7])([F:6])[F:5].C(N(CC)CC)C.[S:30]1[CH:34]=[CH:33][C:32]([S:35](Cl)(=[O:37])=[O:36])=[CH:31]1>ClCCCl>[F:22][C:2]([F:1])([F:21])[C:3]([C:9]1[CH:10]=[CH:11][C:12]([N:15]2[CH2:20][CH2:19][N:18]([S:35]([C:32]3[CH:33]=[CH:34][S:30][CH:31]=3)(=[O:37])=[O:36])[CH2:17][CH2:16]2)=[CH:13][CH:14]=1)([OH:8])[C:4]([F:7])([F:6])[F:5]

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 2776378Thiophene-3-sulfonyl ChlorideHCID 866237611,1,1,3,3,3-Hexafluoro-2-(4-(1-piperazinyl)phenyl)-2-propanol

Produkt 1

HCID 866703021,1,1,3,3,3-Hexafluoro-2-(4-(4-(3-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 111,2-DichloroethaneLösungsmittel

Versuchsvorschrift

To a solution of 1,1,1,3,3,3-hexafluoro-2-(4-(1-piperazinyl)phenyl)-2-propanol (50 mg, 0.152 mmol, published PCT patent application no. WO 2006/094842) and triethylamine (63.6 μL, 0.457 mmol) in 1,2-dichloroethane (1.5 mL) was added 3-thiophenesulfonyl chloride (1M in dichloroethane, 168 μL, 0.168 mmol, ASDI, Newark, Del.). The reaction was shaken on an orbital shaker for 18 h. The reaction solvent was removed under reduced pressure and the crude product was purified by reverse-phase preparative HPLC using a Sunfire Prep C18 OBD (100×19 mm, 5 μm) column, 0.1% TFA in MeOH/H2O, gradient (65% to 95% over 4.5 min) to provide 1,1,1,3,3,3-hexafluoro-2-(4-(4-(3-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol. 1H NMR (400 MHz, DMSO-d6) δ 8.35-8.27 (m, 1H), 7.85 (dd, J=5.1, 2.9 Hz, 1H), 7.47 (d, J=8.8 Hz, 2H), 7.37 (d, J=5.1 Hz, 1H), 7.02 (d, J=9.0 Hz, 2H), 3.33-3.28 (m, 4H), 3.07-3.01 (m, 4H). m/z (ESI, +ve ion) 475.1 (M+H)+. GK-GKRP EC50 (NADPH-coupled)=0.597 μM; GK-GKRP EC50 (LC MS/MS)=0.964 μM.

Aufarbeitung

  1. customThe reaction solvent was removed under reduced pressure
  2. customthe crude product was purified by reverse-phase preparative HPLC
  3. customC18 OBD (100×19 mm, 5 μm) column, 0.1% TFA in MeOH/H2O, gradient (65% to 95% over 4.5 min)

Quellen und Nachweise

ORD-Eintrag
ord-2ac308ec879c48ca8e2e4506ada6fed8
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08431563B2

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