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 1972556Notes

Reaction equation

HRID 1972556 reaction equation
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]

Participants

6

Reactant 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×

Product 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

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

((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

Workup

  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

Sources & evidence

ORD record
ord-19a8e6d2f8b9470e81336e7c3b2f4664
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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