Potassium Carbonate → N-(((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-3-pyridinesulfonamide

HRID 1972569Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1972569
[NH2:1][CH2:2][C@H:3]1[CH2:8][N:7]([S:9]([C:12]2[S:13][CH:14]=[CH:15][CH:16]=2)(=[O:11])=[O:10])[CH2:6][CH2:5][N:4]1[C:17]1[CH:22]=[CH:21][C:20]([C:23]([OH:29])([CH3:28])[C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=1.[N:30]1[CH:35]=[CH:34][CH:33]=[C:32]([S:36](Cl)(=[O:38])=[O:37])[CH:31]=1.C(N(C(C)C)CC)(C)C.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.CN(C)C1C=CN=CC=1>[NH3:1].[S:13]1[CH:14]=[CH:15][CH:16]=[C:12]1[S:9]([N:7]1[CH2:6][CH2:5][N:4]([C:17]2[CH:18]=[CH:19][C:20]([C:23]([OH:29])([CH3:28])[C:24]([F:26])([F:27])[F:25])=[CH:21][CH:22]=2)[C@@H:3]([CH2:2][NH:1][S:36]([C:32]2[CH:31]=[N:30][CH:35]=[CH:34][CH:33]=2)(=[O:38])=[O:37])[CH2:8]1)(=[O:10])=[O:11]

Komponenten

8

Edukt 4

HCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 3164136Pyridine-3-sulfonyl chlorideHCID 665825602-(4-((2S)-2-(aminomethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol

Produkt 2

HCID 222AmmoniaAusbeute 5 %HCID 56932724N-(((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-3-pyridinesulfonamideAusbeute 140,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a solution of 2-(4-((2S)-2-(aminomethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol (0.130 g, 0.289 mmol) in CH2Cl2 (5.0 mL) was added 4-dimethylaminopyridine (7.0 mg, 0.062 mmol, Aldrich, St. Louis, Mo.), 3-pyridinesulfonyl chloride (0.077 g, 0.43 mmol, WAKO, Richmond, Va.), and diisopropylethylamine (0.50 mL, 2.9 mmol). The reaction mixture was heated at 60° C. for 30 min. The solvent was then removed in vacuo, The residue was dissolved in MeOH (5.0 mL) then potassium carbonate (0.240 g, 1.74 mmol) was added. The reaction mixture was heated at 60° C. for 1 h. Then the solvent was removed in vacuo. The residue was partitioned between water (20 mL) and CH2Cl2 (40 mL). The aqueous layer was extracted with CH2Cl2 (2×20 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated. The crude product was purified by column chromatography (24 g of silica gel, 100% first then 5% to 8% 2M NH3 in MeOH in CH2Cl2) to afford N-(((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-3-pyridinesulfonamide (0.120 g) as a mixture of two isomers:

Aufarbeitung

  1. customThe solvent was then removed in vacuo
  2. dissolutionThe residue was dissolved in MeOH (5.0 mL)
  3. temperatureThe reaction mixture was heated at 60° C. for 1 h
  4. customThen the solvent was removed in vacuo
  5. customThe residue was partitioned between water (20 mL) and CH2Cl2 (40 mL)
  6. extractionThe aqueous layer was extracted with CH2Cl2 (2×20 mL)
  7. dry with materialThe combined organic extracts were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by column chromatography (24 g of silica gel, 100% first

Quellen und Nachweise

ORD-Eintrag
ord-eded7281c6ae4cedb3d82606ab0fbfdb
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08431563B2

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