Potassium Carbonate → HCID 66583013, compound

HRID 1972558Notes

Reaction equation

HRID 1972558 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.[CH3:34][CH:35]1[CH2:40][NH:39][C:38](=[O:41])[CH2:37][NH:36]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.CCOC(C)=O>[CH3:34][CH:35]1[CH2:40][NH:39][C:38](=[O:41])[CH2:37][N:36]1[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:14])=[O:15])[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:29])([F:31])[F:30])=[CH:23][CH:22]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 552532585-Methyl-2-piperazinone HClHCID 86670301((2R)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl methanesulfonate2×

Product 1

HCID 66583013HCID 66583013, compoundYield 7.7%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

((2R)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl methanesulfonate (350 mg, 0.662 mmol, Intermediate B) was combined with 5-methylpiperazin-2-one (79 mg, 0.695 mmol, Anichem, North Brunswick, N.J.), potassium carbonate (275 mg, 1.99 mmol, Sigma-Aldrich, St. Louis, Mo.) in acetonitrile (4.41 mL) was heated at 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.). The filtrate was concentrated and 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). The collected fractions were partitioned between CH2Cl2 and saturated aqueous NaHCO3, the organic layer was dried (Na2SO4), filtered and concentrated. The residue was taken up in MeOH and was passed through an AccuBond SPE SCX cartridge eluting with 2M ammonia/MeOH, to give the title compound (28 mg) as a mixture of four diastereomers.

Workup

  1. temperatureto cool to room temperature
  2. customthe solids were removed
  3. filtrationby filtering through a 0.2 μm
  4. filtrationmillipore Millex-FG filter (Millipore, Billerica, Mass.)
  5. concentrationThe filtrate was concentrated
  6. custompurified 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)
  7. customThe collected fractions were partitioned between CH2Cl2 and saturated aqueous NaHCO3
  8. dry with materialthe organic layer was dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. washeluting with 2M ammonia/MeOH

Sources & evidence

ORD record
ord-71d15a17361f4714a30af5cc254113f4
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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