N,N'-Dimethylethylenediamine → (R)-[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl][4-(3-methyl-1,1-dioxo-1lambda6-isothiazolidin-2-yl)phenyl]methanone

HRID 2411514Notes

Reaction equation

HRID 2411514 reaction equation
[CH3:1][C:2]1[C:3]([N:9]2[CH2:14][CH2:13][N:12]([C:15]([C:17]3[CH:22]=[CH:21][C:20](I)=[CH:19][CH:18]=3)=[O:16])[CH2:11][CH2:10]2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.[CH3:24][C@@H:25]1[CH2:29][CH2:28][S:27](=[O:31])(=[O:30])[NH:26]1.C(=O)([O-])[O-].[K+].[K+].CNCCNC>[Cu]I.O.C1(C)C=CC=CC=1>[CH3:1][C:2]1[C:3]([N:9]2[CH2:14][CH2:13][N:12]([C:15]([C:17]3[CH:22]=[CH:21][C:20]([N:26]4[C@H:25]([CH3:24])[CH2:29][CH2:28][S:27]4(=[O:31])=[O:30])=[CH:19][CH:18]=3)=[O:16])[CH2:11][CH2:10]2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1

Participants

8

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 11430Potassium CarbonateHCID 16664802(R)-3-methylisothiazolidine 1,1-dioxideHCID 58484535[4-(3,5-Dimethylpyridin-2-yl)piperazin-1-yl](4-iodophenyl)methanone

Product 1

HCID 71252266(R)-[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl][4-(3-methyl-1,1-dioxo-1lambda6-isothiazolidin-2-yl)phenyl]methanone

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a mixture of [4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl](4-iodophenyl)methanone (848 mg) described in Preparation Example 113, (R)-3-methylisothiazolidine 1,1-dioxide (272 mg) described in Preparation Example 2, potassium carbonate (555 mg) and copper(I) iodide (192 mg) were added toluene (4 mL) and N,N′-dimethylethylenediamine (0.20 mL), and the mixture was stirred with heating under reflux for 8 hr. The reaction mixture was cooled, water was added, the mixture was extracted with chloroform, and the solvent was evaporated. The obtained residue was purified by column chromatography (chloroform:methanol) to give (R)-[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl][4-(3-methyl-1,1-dioxo-1λ6-isothiazolidin-2-yl)phenyl]methanone. The obtained (R)-[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl][4-(3-methyl-1,1-dioxo-1λ6-isothiazolidin-2-yl)phenyl]methanone (453 mg) was dissolved in ethyl acetate, 4N hydrogen chloride/ethyl acetate (0.26 mL) was added, and the precipitate was collected by filtration to give the title compound (372 mg).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for 8 hr
  3. temperatureThe reaction mixture was cooled
  4. extractionthe mixture was extracted with chloroform
  5. customthe solvent was evaporated
  6. customThe obtained residue was purified by column chromatography (chloroform:methanol)

Sources & evidence

ORD record
ord-e093c8ff858647c79223e005e0b443b2
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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