Potassium Carbonate → HCID 86670371, compound

HRID 1972500Notes

Reaction equation

HRID 1972500 reaction equation
[Br:1][C:2]1[S:6][C:5]([S:7]([N:10]2[CH2:15][CH2:14][NH:13][C@@H:12]([CH2:16][CH:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[CH2:11]2)(=[O:9])=[O:8])=[CH:4][CH:3]=1.Cl[C:24]1[N:29]=[CH:28][C:27]([C:30]([OH:39])([C:35]([F:38])([F:37])[F:36])[C:31]([F:34])([F:33])[F:32])=[CH:26][N:25]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O.CCOC(C)=O>[Br:1][C:2]1[S:6][C:5]([S:7]([N:10]2[CH2:15][CH2:14][N:13]([C:24]3[N:25]=[CH:26][C:27]([C:30]([OH:39])([C:31]([F:32])([F:33])[F:34])[C:35]([F:37])([F:38])[F:36])=[CH:28][N:29]=3)[C@@H:12]([CH2:16][CH:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[CH2:11]2)(=[O:8])=[O:9])=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 66582612HCID 66582612, compoundHCID 866703482-(2-Chloropyrimidin-5-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol2×

Product 1

HCID 86670371HCID 86670371, compoundYield 46.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (3S)-1-((5-bromo-2-thiophenyl)sulfonyl)-3-(tetrahydro-2H-pyran-4-ylmethyl)piperazine (190 mg, 0.464 mmol, Example 133, Step 1), 2-(2-chloropyrimidin-5-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol (156 mg, 0.557 mmol, Intermediate D), and potassium carbonate (128 mg, 0.928 mmol) in DMF was heated at 100° C. and stirred for 16 h. The mixture was diluted with water (20 mL) and EtOAc (20 mL). The layers were separated and the organics were washed with water (20 mL) and brine (20 mL). The organic extracts were dried over MgSO4, filtered, and concentrated. The crude material was absorbed onto silica gel and purified via column chromatography (40 g silica gel, 0 to 100% EtOAc in hexanes) to give (S)-2-(2-(4-(5-bromothiophen-2-ylsulfonyl)-2-((tetrahydro-2H-pyran-4-yl)methyl)piperazin-1-yl)pyrimidin-5-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol (140 mg).

Workup

  1. customThe layers were separated
  2. washthe organics were washed with water (20 mL) and brine (20 mL)
  3. dry with materialThe organic extracts were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was absorbed onto silica gel
  7. custompurified via column chromatography (40 g silica gel, 0 to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-abc063a09c2a4c3390a26ce7d0775f5a
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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