Hydrogen chloride-ethyl acetate → (R)-[2-fluoro-4-(3-methyl-1,1-dioxo-1lambda6-isothiazolidin-2-yl)phenyl][4-(3,5,6-trimethylpyridin-2-yl)piperazin-1-yl]methanone hydrochloride

HRID 2411551Notes

Reaction equation

HRID 2411551 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N:8]2[C@H:12]([CH3:13])[CH2:11][CH2:10][S:9]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])=[C:26]([CH3:32])[N:25]=2)[CH2:20][CH2:19]1)=[O:17].[ClH:33].C(OCC)(=O)C>C(OCC)(=O)C>[ClH:33].[F:1][C:2]1[CH:7]=[C:6]([N:8]2[C@H:12]([CH3:13])[CH2:11][CH2:10][S:9]2(=[O:15])=[O:14])[CH:5]=[CH:4][C:3]=1[C:16]([N:18]1[CH2:19][CH2:20][N:21]([C:24]2[C:29]([CH3:30])=[CH:28][C:27]([CH3:31])=[C:26]([CH3:32])[N:25]=2)[CH2:22][CH2:23]1)=[O:17]

Participants

4

Reactant 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 71252952(R)-[2-fluoro-4-(3-methyl-1,1-dioxo-1lambda6-isothiazolidin-2-yl)phenyl][4-(3,5,6-trimethylpyridin-2-yl)piperazin-1-yl]methanone

Product 1

HCID 71252951(R)-[2-fluoro-4-(3-methyl-1,1-dioxo-1lambda6-isothiazolidin-2-yl)phenyl][4-(3,5,6-trimethylpyridin-2-yl)piperazin-1-yl]methanone hydrochloride

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of (4-bromo-2-fluorophenyl)[4-(3,5,6-trimethylpyridin-2-yl)piperazin-1-yl]methanone (322 mg) described in Preparation Example 128, (R)-3-methylisothiazolidine 1,1-dioxide (107 mg) described in Preparation Example 2, potassium carbonate (220 mg), copper(I) iodide (76 mg) and potassium iodide (132 mg) were added toluene (1 mL) and N,N′-dimethylethylenediamine (80 μL), 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 (ethyl acetate:hexane) to give (R)-[2-fluoro-4-(3-methyl-1,1-dioxo-1λ6-isothiazolidin-2-yl)phenyl][4-(3,5,6-trimethylpyridin-2-yl)piperazin-1-yl]methanone. The obtained (R)-[2-fluoro-4-(3-methyl-1,1-dioxo-1λ6-isothiazolidin-2-yl)phenyl][4-(3,5,6-trimethylpyridin-2-yl)piperazin-1-yl]methanone (140 mg) was dissolved in ethyl acetate, 4N hydrogen chloride/ethyl acetate (0.08 mL) was added, and the precipitate was collected by filtration to give the title compound (166 mg).

Workup

  1. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-590e53bbff424563bda874e7c837ae55
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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