Ammonia → 2-[4-(3,5-Dimethylpyridin-2-yl)piperazine-1-carbonyl]-5-(1,1-dioxo-1lambda6-isothiazolidin-2-ylmethyl)benzonitrile

HRID 2411850Notes

Reaction equation

HRID 2411850 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][S:10]2(=[O:15])=[O:14])[CH:5]=[CH:4][C:3]=1[C:16]([N:18]1[CH2:23][CH2:22][N:21]([C:24]2[C:29]([CH3:30])=[CH:28][C:27]([CH3:31])=[CH:26][N:25]=2)[CH2:20][CH2:19]1)=[O:17].O.N.[CH3:34][N:35](C)C=O>[C-]#N.[Zn+2].[C-]#N>[CH3:30][C:29]1[C:24]([N:21]2[CH2:22][CH2:23][N:18]([C:16]([C:3]3[CH:4]=[CH:5][C:6]([CH2:8][N:9]4[CH2:13][CH2:12][CH2:11][S:10]4(=[O:15])=[O:14])=[CH:7][C:2]=3[C:34]#[N:35])=[O:17])[CH2:19][CH2:20]2)=[N:25][CH:26]=[C:27]([CH3:31])[CH:28]=1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 962WaterHCID 6228DimethylformamideHCID 71252686[2-Bromo-4-(1,1-dioxo-1lambda6-isothiazolidin-2-ylmethyl)phenyl][4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanone

Product 1

HCID 712526912-[4-(3,5-Dimethylpyridin-2-yl)piperazine-1-carbonyl]-5-(1,1-dioxo-1lambda6-isothiazolidin-2-ylmethyl)benzonitrile

Reagents, catalysts & solvents 1

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst

Conditions

Temperature
130 °C

Procedure

Under a nitrogen stream, [2-bromo-4-(1,1-dioxo-1λ6-isothiazolidin-2-ylmethyl)phenyl][4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanone (120 mg) described in Example 461 was dissolved in N,N-dimethylformamide (5 mL), zinc cyanide (28 mg) and tetrakistriphenylphosphine palladium(0)(55 mg) were added, and the mixture was stirred at 130° C. for 4 hr. After completion of the reaction, to the reaction mixture was added water/saturated aqueous ammonium chloride solution/28% aqueous ammonia (4:4:1), and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and the solvent was evaporated. The obtained residue was purified by column chromatography (hexane:ethyl acetate) to give the title compound (68 mg).

Workup

  1. customAfter completion of the reaction
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with water and saturated brine
  4. customthe solvent was evaporated
  5. customThe obtained residue was purified by column chromatography (hexane:ethyl acetate)

Sources & evidence

ORD record
ord-4e111eeb38224b27a6e53fee4b6d6729
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

Loading…