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

HRID 1972622Notes

Reaction equation

HRID 1972622 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.[C:30]1(=O)[CH2:33][CH2:32][CH2:31]1.C[Si](C)(C)[C:37]#[N:38]>ClCCCl>[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][C:30]2([C:37]#[N:38])[CH2:33][CH2:32][CH2:31]2)[CH2:8]1)(=[O:10])=[O:11]

Participants

5

Reactant 3

HCID 14496CyclobutanoneHCID 82115Trimethylsilyl cyanideHCID 665825602-(4-((2S)-2-(aminomethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol

Product 1

HCID 665824991-((((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)amino)cyclobutanecarbonitrileYield 83.6%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

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 (0.202 g, 0.448 mmol, Example 192, Step 2), cyclobutanone (0.0364 g, 0.519 mmol, Alfa Aesar, Ward Hill, Mass.) and 1,2-dichloroethane (2.5 mL). The solution was stirred at room temperature for 20 min then trimethylsilanecarbonitrile (0.120 mL, 0.959 mmol, Sigma-Aldrich, St. Louis, Mo.) was added. After stirring at room temperature for 12 h, the material was purified by column chromatography (10 g of silica, 20 to 70% EtOAc in hexanes) to afford 1-((((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)amino)cyclobutanecarbonitrile (0.198 g) as a white solid.

Workup

  1. stirringAfter stirring at room temperature for 12 h
  2. customthe material was purified by column chromatography (10 g of silica, 20 to 70% EtOAc in hexanes)

Sources & evidence

ORD record
ord-73a54d8de2664c9cae3a37185f579fa0
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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