4-Methoxybenzylamine → HCID 71252175, compound

HRID 2411601Notes

Reaction equation

HRID 2411601 reaction equation
[CH2:1]([C:3]1[CH:4]=[C:5]([CH3:25])[C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]([C:17]3[CH:18]=[N:19][C:20](F)=[CH:21][C:22]=3[CH3:23])=[O:16])[CH2:11][CH2:10]2)=[N:7][CH:8]=1)[CH3:2].[CH3:26][O:27][C:28]1[CH:35]=[CH:34][C:31]([CH2:32][NH2:33])=[CH:30][CH:29]=1>O>[CH2:1]([C:3]1[CH:4]=[C:5]([CH3:25])[C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]([C:17]3[CH:18]=[N:19][C:20]([NH:33][CH2:32][C:31]4[CH:34]=[CH:35][C:28]([O:27][CH3:26])=[CH:29][CH:30]=4)=[CH:21][C:22]=3[CH3:23])=[O:16])[CH2:11][CH2:10]2)=[N:7][CH:8]=1)[CH3:2]

Participants

4

Reactant 2

HCID 754524-MethoxybenzylamineHCID 58484602[4-(5-Ethyl-3-methylpyridin-2-yl)piperazin-1-yl](6-fluoro-4-methylpyridin-3-yl)methanone

Product 1

HCID 71252175HCID 71252175, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
160 °C

Procedure

To [4-(5-ethyl-3-methylpyridin-2-yl)piperazin-1-yl](6-fluoro-4-methylpyridin-3-yl)methanone (320 mg) described in Preparation Example 176 was added 4-methoxybenzylamine (1 mL), and the mixture was stirred at 160° C. for 6 hr. The reaction mixture was cooled, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated. The obtained residue was purified by column chromatography (hexane:ethyl acetate) to give [4-(5-ethyl-3-methylpyridin-2-yl)piperazin-1-yl][6-(4-methoxybenzylamino)-4-methylpyridin-3-yl)methanone (330 mg). The obtained [4-(5-ethyl-3-methylpyridin-2-yl)piperazin-1-yl][6-(4-methoxybenzylamino)-4-methylpyridin-3-yl)methanone (330 mg) was dissolved in dichloromethane (5 mL), trifluoroacetic acid (10 mL) was added, and the mixture was stirred at room temperature overnight. The solvent was evaporated from the reaction mixture, 1N aqueous sodium hydroxide solution was added, and the mixture was extracted with chloroform. The organic layer was washed with saturated brine, and the solvent was evaporated. The obtained residue was purified by column chromatography to give (6-amino-4-methylpyridin-3-yl) [4-(5-ethyl-3-methylpyridin-2-yl)piperazin-1-yl]methanone. The obtained (6-amino-4-methylpyridin-3-yl)[4-(5-ethyl-3-methylpyridin-2-yl)piperazin-1-yl]methanone and triethylamine (0.30 mL) were dissolved in dichloromethane (10 mL), 3-chloropropane-1-sulfonyl chloride (0.18 mL) was added under ice-cooling, and the mixture was stirred at room temperature for 3.5 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 (10 mL), 1,8-diazabicyclo[5.4.0]undec-7-ene (0.16 mL) was 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 organic layer was washed with water and saturated brine, and the solvent was evaporated. The obtained residue was purified by column chromatography to give the title compound (220 mg).

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. customthe solvent was evaporated
  5. customThe obtained residue was purified by column chromatography (hexane:ethyl acetate)

Sources & evidence

ORD record
ord-78a8fac0a43a4034ad9d3dc3cdefdbf1
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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