Dimethylformamide → 4-{1-Methyl-1-[4-(toluene-4-sulfonyl)-piperazin-1-yl]-ethyl]-benzonitrile

HRID 717076Notes

Reaction equation

HRID 717076 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:11]2[CH2:16][CH2:15][N:14]([S:17]([C:20]3[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=3)(=[O:19])=[O:18])[CH2:13][CH2:12]2)([CH3:10])[CH3:9])=[CH:4][CH:3]=1.[CH3:27][N:28](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:9][C:8]([C:5]1[CH:6]=[CH:7][C:2]([C:27]#[N:28])=[CH:3][CH:4]=1)([N:11]1[CH2:16][CH2:15][N:14]([S:17]([C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=2)(=[O:19])=[O:18])[CH2:13][CH2:12]1)[CH3:10]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 898128531-[1-(4-Bromo-phenyl)-1-methyl-ethyl]-4-(toluene-4-sulfonyl)-piperazine

Product 1

HCID 898128254-{1-Methyl-1-[4-(toluene-4-sulfonyl)-piperazin-1-yl]-ethyl]-benzonitrileYield 47%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Procedure

To a solution of 1-[1-(4-bromo-phenyl)-1-methyl-ethyl]-4-(toluene-4-sulfonyl)-piperazine (200 mg, 0.45 mmol) in DMF (3 mL) was added zinc cyanide (64.41 mg, 0.54 mmol) and tetrakis(triphenylphosphine)palladium(0) (52 mg, 0.045 mmol) and the reaction mixture degassed for 10 min under N2. The reaction mixture was then subjected to microwave irradiation for 30 min at 180° C., afterwhich time the reaction was diluted with 1:1 CH2Cl2/EtOAc (20 mL), washed with water (2×10 mL), passed through a phase separation cartridge and concentrated in vacuo. The crude residue was purified by reverse phase preparative HPLC-MS to afford 4-{1-methyl-1-[4-(toluene-4-sulfonyl)-piperazin-1-yl]-ethyl]-benzonitrile as a cream solid (70 mg, 47%).

Workup

  1. customthe reaction mixture degassed for 10 min under N2
  2. customirradiation for 30 min at 180° C.
  3. additionafterwhich time the reaction was diluted with 1:1 CH2Cl2/EtOAc (20 mL)
  4. washwashed with water (2×10 mL)
  5. custompassed through a phase separation cartridge
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was purified by reverse phase preparative HPLC-MS

Sources & evidence

ORD record
ord-22488617e9db48ec96da092b6bfaf5bc
Source dataset
uspto-grants-2015_11
Patent number
US09193689B2

Reaction notes

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