Acetone → 2-methyl-2-((((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)amino)propanenitrile

HRID 1972598Notes

Reaction equation

HRID 1972598 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.[CH3:30][C:31]([CH3:33])=O.C[Si]([C:38]#[N:39])(C)C>CCO>[CH3:30][C:31]([NH: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:10])=[O:11])[CH2:6][CH2:5][N:4]1[C:17]1[CH:18]=[CH:19][C:20]([C:23]([OH:29])([CH3:28])[C:24]([F:26])([F:27])[F:25])=[CH:21][CH:22]=1)([CH3:33])[C:38]#[N:39]

Participants

5

Reactant 3

HCID 180AcetoneHCID 82115Trimethylsilyl cyanideHCID 665825602-(4-((2S)-2-(aminomethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol

Product 1

HCID 665828112-methyl-2-((((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)amino)propanenitrileYield 52.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
0 °C

Procedure

A 5-mL vial was charged with 2-(4-((2S)-2-(aminomethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol (0.0521 g, 0.116 mmol, Example 192, Step 2), acetone (10 μL, 0.14 mmol) and EtOH (1 mL). The reaction mixture was cooled to 0° C. and stirred for 35 min. Trimethylsilyl cyanide (46.3 μL, 0.348 mmol, Sigma-Aldrich, St. Louis, Mo.) was added drop wise at 0° C. The mixture was slowly allowed to warm up to room temperature and stirred for 12 h. The solvent was removed and the remaining white residue was dissolved into EtOAc and passed through a pad of silica gel rinsing with EtOAc as eluent. The solvent was removed and the crude product was purified by column chromatography (10 g of silica gel, 50 to 100% EtOAc in hexanes) to afford 2-methyl-2-((((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)amino)propanenitrile (0.0312 g) as an off-white solid.

Workup

  1. temperatureto warm up to room temperature
  2. stirringstirred for 12 h
  3. customThe solvent was removed
  4. dissolutionthe remaining white residue was dissolved into EtOAc
  5. customThe solvent was removed
  6. customthe crude product was purified by column chromatography (10 g of silica gel, 50 to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-6ed6932a10f041d8901ec1e0d633471b
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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