Hydrochloric Acid → [4-Bromo-2-(1,1-dioxoisothiazolidin-2-yl)phenyl][4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanone

HRID 2411302Notes

Reaction equation

HRID 2411302 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8]C)=O)=[C:4]([N:12]2[CH2:16][CH2:15][CH2:14][S:13]2(=[O:18])=[O:17])[CH:3]=1.[OH-].[Na+].Cl.[CH3:22][C:23]1[C:24]([N:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)=[N:25][CH:26]=[C:27]([CH3:29])[CH:28]=1.O.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>CO.O>[Br:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([N:33]2[CH2:34][CH2:35][N:30]([C:24]3[C:23]([CH3:22])=[CH:28][C:27]([CH3:29])=[CH:26][N:25]=3)[CH2:31][CH2:32]2)=[O:8])=[C:4]([N:12]2[CH2:16][CH2:15][CH2:14][S:13]2(=[O:18])=[O:17])[CH:3]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 231494114-(4,6-Dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrateHCID 584844961-(3,5-Dimethylpyridin-2-yl)piperazineHCID 58484624Methyl 4-bromo-2-(1,1-dioxoisothiazolidin-2-yl)benzoate

Product 1

HCID 58484716[4-Bromo-2-(1,1-dioxoisothiazolidin-2-yl)phenyl][4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanoneYield 81.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent

Conditions

Temperature
65 °C

Procedure

Methyl 4-bromo-2-(1,1-dioxo-1λ6-isothiazolidin-2-yl)benzoate (2 g) described in Preparation Example 13 was dissolved in methanol (18 mL), 1N aqueous sodium hydroxide solution (9 mL) was added, and the mixture was stirred at 60-70° C. To the reaction mixture was added 1N hydrochloric acid (9 mL), a solution of 1-(3,5-dimethylpyridin-2-yl)piperazine (1.14 g) described in Preparation Example 79 in methanol (2 mL) and 4-(4,6-dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (DMT-MM) (1.65 g) were added, and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The solvent was evaporated from the organic layer, and the residue was purified by column chromatography (hexane:ethyl acetate) to give the title compound (2.4 g).

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. extractionthe mixture was extracted with ethyl acetate
  3. customThe solvent was evaporated from the organic layer
  4. customthe residue was purified by column chromatography (hexane:ethyl acetate)

Sources & evidence

ORD record
ord-69e26126bb5b4d13951588388c5547a6
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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