Potassium Carbonate → HCID 56932721, compound

HRID 1972554Notes

Reaction equation

HRID 1972554 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.[NH:34]1[CH2:39][CH2:38][NH:37][CH2:36][C:35]1=[O:40].C(=O)([O-])[O-].[K+].[K+]>C(#N)C.CCOC(C)=O>[S:17]1[CH:18]=[CH:19][CH:20]=[C:16]1[S:13]([N:11]1[CH2:10][CH2:9][N:8]([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)[C@@H:7]([CH2:6][N:37]2[CH2:38][CH2:39][NH:34][C:35](=[O:40])[CH2:36]2)[CH2:12]1)(=[O:14])=[O:15]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 231360Piperazin-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 56932721HCID 56932721, compoundYield 44.7%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

((2R)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl methanesulfonate (100 mg, 0.189 mmol, Intermediate B) was combined with piperazin-2-one (18.9 mg, 0.189 mmol, Alfa-Aesar) and potassium carbonate (78 mg, 0.57 mmol, Sigma-Aldrich, St. Louis, Mo.) in acetonitrile (1.89 mL) and heated at 130° 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 silica gel chromatography (0 to 7% MeOH in CH2Cl2) followed by purification via 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 and then the organic extracts were 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 in MeOH to give the title compound (45 mg) as a mixture of two isomers.

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. customAfter concentration of the filtrate, the crude residue was purified by silica gel chromatography (0 to 7% MeOH in CH2Cl2)
  6. customfollowed by purification via 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 extracts were dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. washeluting with 2M ammonia in MeOH

Sources & evidence

ORD record
ord-2557373e890643058834f1f3027d9923
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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