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

HRID 1972556Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1972556
CS(O[CH2:6][C@H:7]1[CH2:12][N:11]([S:13]([C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)(=[O:15])=[O:14])[CH2:10][CH2:9][N:8]1[C:21]1[CH:26]=[CH:25][C:24]([C:27]([OH:33])([CH3:32])[C:28]([F:31])([F:30])[F:29])=[CH:23][CH:22]=1)(=O)=O.[CH:34]([CH:37]1[NH:42][CH2:41][CH2:40][NH:39][C:38]1=[O:43])([CH3:36])[CH3:35].C(=O)([O-])[O-].[K+].[K+]>C(#N)C.CCOC(C)=O>[CH3:35][CH:34]([CH:37]1[N:42]([CH2:6][C@H:7]2[CH2:12][N:11]([S:13]([C:16]3[S:17][CH:18]=[CH:19][CH:20]=3)(=[O:14])=[O:15])[CH2:10][CH2:9][N:8]2[C:21]2[CH:22]=[CH:23][C:24]([C:27]([OH:33])([CH3:32])[C:28]([F:31])([F:30])[F:29])=[CH:25][CH:26]=2)[CH2:41][CH2:40][NH:39][C:38]1=[O:43])[CH3:36]

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 448908153-(Propan-2-yl)piperazin-2-oneHCID 86670301((2R)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl methanesulfonate2×

Produkt 1

HCID 569326773-(1-methylethyl)-4-(((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-2-piperazinone

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6342AcetonitrileLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

((2R)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl methanesulfonate (250 mg, 0.473 mmol, Intermediate B), 3-isopropylpiperazin-2-one (67.3 mg, 0.473 mmol, ChemBridge, San Diego, Calif.), and potassium carbonate (196 mg, 1.419 mmol, Sigma-Aldrich, St. Louis, Mo.) in acetonitrile (3.15 mL) was heated to 120° C. for 30 min After the reaction was allowed to cool to room temperature, the mixture was diluted with EtOAc and the solids were removed by filtering through a 0.2 μm millipore Millex-FG filter (Millipore, Billerica, Mass.). After concentration of the filtrate, the crude residue was purified by reverse-phase HPLC, (Phenomenex Gemini-NX 10μ, 110 Å, AXIA packed column, 100×50 mm, 60 mL/min, 10-95% CH3CN/H2O, 0.1% TFA, 10 min gradient), two peaks were collected and each was partitioned between CH2Cl2 and saturated aqueous NaHCO3, the organic layers were dried (Na2SO4), filtered and concentrated to give 4 isomeric products

Aufarbeitung

  1. customthe solids were removed
  2. filtrationby filtering through a 0.2 μm
  3. filtrationmillipore Millex-FG filter (Millipore, Billerica, Mass.)
  4. customAfter concentration of the filtrate, the crude residue was purified by reverse-phase HPLC, (Phenomenex Gemini-NX 10μ, 110 Å, AXIA packed column, 100×50 mm, 60 mL/min, 10-95% CH3CN/H2O, 0.1% TFA, 10 min gradient), two peaks
  5. customwere collected
  6. customeach was partitioned between CH2Cl2 and saturated aqueous NaHCO3
  7. dry with materialthe organic layers were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give 4 isomeric products

Quellen und Nachweise

ORD-Eintrag
ord-19a8e6d2f8b9470e81336e7c3b2f4664
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08431563B2

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