Methyl p-toluenesulfonate → HCID 71252429, compound

HRID 2411653Notes

Reaction equation

HRID 2411653 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]([N:23]4[C@@H:27]([CH2:28][OH:29])[CH2:26][CH2:25][C:24]4=[O:30])=[CH:19][C:18]=3[F:31])=[O:16])[CH2:11][CH2:10]2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.[H-].[Na+].O1CCC[CH2:35]1.S(C1C=CC(C)=CC=1)(OC)(=O)=O>O.CN(C)C=O>[CH3:1][C:2]1[C:3]([N:9]2[CH2:10][CH2:11][N:12]([C:15]([C:17]3[CH:22]=[CH:21][C:20]([N:23]4[C@@H:27]([CH2:28][O:29][CH3:35])[CH2:26][CH2:25][C:24]4=[O:30])=[CH:19][C:18]=3[F:31])=[O:16])[CH2:13][CH2:14]2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1

Participants

7

Reactant 4

HCID 6645Methyl p-toluenesulfonateHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 71252056HCID 71252056, compound

Product 1

HCID 71252429HCID 71252429, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Using (R)-5-hydroxymethylpyrrolidin-2-one (138 mg) and (4-bromo-2-fluorophenyl)[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanone (392 mg) described in Preparation Example 114 and by the reaction and treatment in the same manner as in Example 1, (R)-1-{4-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]-3-fluorophenyl}-5-hydroxymethylpyrrolidin-2-one (330 mg) was obtained. To a mixture of the obtained (R)-1-{4-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]-3-fluorophenyl}-5-hydroxymethylpyrrolidin-2-one (330 mg) and sodium hydride (37 mg) were added tetrahydrofuran and N,N-dimethylformamide, and the mixture was stirred at room temperature for 15 min. To the reaction mixture was added methyl tosylate (117 μL), and the mixture was further stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over sodium sulfate, and the solvent was evaporated. The obtained residue was purified by column chromatography (hexane:ethyl acetate) to give (R)-1-{4-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]-3-fluorophenyl}-5-methoxymethylpyrrolidin-2-one. The obtained (R)-1-{4-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]-3-fluorophenyl}-5-methoxymethylpyrrolidin-2-one was dissolved in ethyl acetate, 4N hydrogen chloride/ethyl acetate was added and the mixture was stirred. The reaction mixture was concentrated under reduced pressure, diethyl ether was added, and the precipitate was collected by filtration to give the title compound (48 mg).

Workup

  1. stirringthe mixture was further stirred at room temperature overnight
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over sodium sulfate
  5. customthe solvent was evaporated
  6. customThe obtained residue was purified by column chromatography (hexane:ethyl acetate)

Sources & evidence

ORD record
ord-e3222f1b13a24c2f8f4c13d96df0598d
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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