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

HRID 1972569Notes

Reaction equation

HRID 1972569 reaction equation
[NH2:1][CH2:2][C@H:3]1[CH2:8][N:7]([S:9]([C:12]2[S:13][CH:14]=[CH:15][CH:16]=2)(=[O:11])=[O:10])[CH2:6][CH2:5][N:4]1[C:17]1[CH:22]=[CH:21][C:20]([C:23]([OH:29])([CH3:28])[C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=1.[N:30]1[CH:35]=[CH:34][CH:33]=[C:32]([S:36](Cl)(=[O:38])=[O:37])[CH:31]=1.C(N(C(C)C)CC)(C)C.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.CN(C)C1C=CN=CC=1>[NH3:1].[S:13]1[CH:14]=[CH:15][CH:16]=[C:12]1[S:9]([N:7]1[CH2:6][CH2:5][N:4]([C:17]2[CH:18]=[CH:19][C:20]([C:23]([OH:29])([CH3:28])[C:24]([F:26])([F:27])[F:25])=[CH:21][CH:22]=2)[C@@H:3]([CH2:2][NH:1][S:36]([C:32]2[CH:31]=[N:30][CH:35]=[CH:34][CH:33]=2)(=[O:38])=[O:37])[CH2:8]1)(=[O:10])=[O:11]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 3164136Pyridine-3-sulfonyl chlorideHCID 665825602-(4-((2S)-2-(aminomethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol

Product 2

HCID 222AmmoniaYield 5%HCID 56932724N-(((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-3-pyridinesulfonamideYield 140.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-(4-((2S)-2-(aminomethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol (0.130 g, 0.289 mmol) in CH2Cl2 (5.0 mL) was added 4-dimethylaminopyridine (7.0 mg, 0.062 mmol, Aldrich, St. Louis, Mo.), 3-pyridinesulfonyl chloride (0.077 g, 0.43 mmol, WAKO, Richmond, Va.), and diisopropylethylamine (0.50 mL, 2.9 mmol). The reaction mixture was heated at 60° C. for 30 min. The solvent was then removed in vacuo, The residue was dissolved in MeOH (5.0 mL) then potassium carbonate (0.240 g, 1.74 mmol) was added. The reaction mixture was heated at 60° C. for 1 h. Then the solvent was removed in vacuo. The residue was partitioned between water (20 mL) and CH2Cl2 (40 mL). The aqueous layer was extracted with CH2Cl2 (2×20 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated. The crude product was purified by column chromatography (24 g of silica gel, 100% first then 5% to 8% 2M NH3 in MeOH in CH2Cl2) to afford N-(((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-3-pyridinesulfonamide (0.120 g) as a mixture of two isomers:

Workup

  1. customThe solvent was then removed in vacuo
  2. dissolutionThe residue was dissolved in MeOH (5.0 mL)
  3. temperatureThe reaction mixture was heated at 60° C. for 1 h
  4. customThen the solvent was removed in vacuo
  5. customThe residue was partitioned between water (20 mL) and CH2Cl2 (40 mL)
  6. extractionThe aqueous layer was extracted with CH2Cl2 (2×20 mL)
  7. dry with materialThe combined organic extracts were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by column chromatography (24 g of silica gel, 100% first

Sources & evidence

ORD record
ord-eded7281c6ae4cedb3d82606ab0fbfdb
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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