Water → HCID 71252521, compound

HRID 2411595Notes

Reaction equation

HRID 2411595 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][N:13]([C:16]3[C:21]([CH3:22])=[CH:20][C:19]([CH3:23])=[CH:18][N:17]=3)[CH2:12][CH2:11]2)=[O:9])=[C:4]([CH3:24])[CH:3]=1.C(N(CC)CC)C.Cl[CH2:33][CH2:34][CH2:35][S:36](Cl)(=[O:38])=[O:37].O>ClCCl>[CH3:22][C:21]1[C:16]([N:13]2[CH2:14][CH2:15][N:10]([C:8]([C:5]3[CH:6]=[N:7][C:2]([N:1]4[CH2:33][CH2:34][CH2:35][S:36]4(=[O:38])=[O:37])=[CH:3][C:4]=3[CH3:24])=[O:9])[CH2:11][CH2:12]2)=[N:17][CH:18]=[C:19]([CH3:23])[CH:20]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 154103-Chloropropanesulphonyl chlorideHCID 71252596HCID 71252596, compound

Product 1

HCID 71252521HCID 71252521, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To [4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl](6-fluoro-4-methylpyridin-3-yl)methanone (840 mg) described in Preparation Example 146 was added 4-methoxybenzylamine (2 mL), and the mixture was stirred at 160° C. for 2.5 hr. The reaction mixture was cooled, water was added, and the mixture was extracted with chloroform. The organic layer was washed with saturated brine, and the solvent was evaporated. To the obtained residue was added diethyl ether, and the insoluble material was collected by filtration to give [4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl][6-(4-methoxybenzylamino)-4-methylpyridin-3-yl)methanone (790 mg). The obtained [4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl][6-(4-methoxybenzylamino)-4-methylpyridin-3-yl)methanone (790 mg) was dissolved in dichloromethane (8 mL), trifluoroacetic acid (13 mL) was added, and the mixture was stirred at room temperature overnight. The solvent was evaporated from the reaction mixture, saturated aqueous sodium hydrogen carbonate solution was added, and the mixture was extracted with chloroform. The organic layer was washed with saturated brine, and the solvent was evaporated to give (6-amino-4-methylpyridin-3-yl)[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanone. The obtained (6-amino-4-methylpyridin-3-yl)[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanone and triethylamine (0.75 mL) were dissolved in dichloromethane (10 mL), 3-chloropropane-1-sulfonyl chloride (0.49 mL) was added under ice-cooling, and the mixture was stirred at room temperature for 3 hr. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was washed with saturated brine, and the solvent was evaporated. The obtained residue was dissolved in N,N-dimethylformamide (7 mL), 1,8-diazabicyclo[5.4.0]undec-7-ene (0.32 mL) was added, and the mixture was stirred at room temperature for 4.5 hr. Water was added to the reaction mixture, 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 to give [4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl][6-(1,1-dioxo-1λ6-isothiazolidin-2-yl)-4-methylpyridin-3-yl]methanone. The obtained [4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl][6-(1,1-dioxo-1λ6-isothiazolidin-2-yl)-4-methylpyridin-3-yl]methanone was dissolved in dichloromethane, 1N hydrogen chloride/diethyl ether was added, and the precipitate was collected by filtration to give the title compound (385 mg).

Workup

  1. temperaturecooling
  2. extractionthe mixture was extracted with chloroform
  3. washThe organic layer was washed with saturated brine
  4. customthe solvent was evaporated
  5. dissolutionThe obtained residue was dissolved in N,N-dimethylformamide (7 mL)
  6. addition1,8-diazabicyclo[5.4.0]undec-7-ene (0.32 mL) was added
  7. stirringthe mixture was stirred at room temperature for 4.5 hr
  8. additionWater was added to the reaction mixture
  9. extractionthe mixture was extracted with ethyl acetate
  10. washThe organic layer was washed with water and saturated brine
  11. customthe solvent was evaporated
  12. customThe obtained residue was purified by column chromatography

Sources & evidence

ORD record
ord-e0c8ae845af6488689ea9ef3fc7e4709
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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