Trifluoroacetic acid → (6-Amino-4-methylpyridin-3-yl) [4-(5-ethyl-3-methylpyridin-2-yl)piperazin-1-yl]methanone

HRID 2411602ノート

反応式

HRID 2411602 の反応式
[CH2:1]([C:3]1[CH:4]=[C:5]([CH3:34])[C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]([C:17]3[CH:18]=[N:19][C:20]([NH:24]CC4C=CC(OC)=CC=4)=[CH:21][C:22]=3[CH3:23])=[O:16])[CH2:11][CH2:10]2)=[N:7][CH:8]=1)[CH3:2].FC(F)(F)C(O)=O>ClCCl>[NH2:24][C:20]1[N:19]=[CH:18][C:17]([C:15]([N:12]2[CH2:13][CH2:14][N:9]([C:6]3[C:5]([CH3:34])=[CH:4][C:3]([CH2:1][CH3:2])=[CH:8][N:7]=3)[CH2:10][CH2:11]2)=[O:16])=[C:22]([CH3:23])[CH:21]=1

参加物

4

反応物 2

HCID 6422Trifluoroacetic acidHCID 71252175[4-(5-Ethyl-3-methylpyridin-2-yl)piperazin-1-yl][6-(4-methoxybenzylamino)-4-methylpyridin-3-yl)methanone

生成物 1

HCID 71253103(6-Amino-4-methylpyridin-3-yl) [4-(5-ethyl-3-methylpyridin-2-yl)piperazin-1-yl]methanone

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  1. customThe solvent was evaporated from the reaction mixture, 1N aqueous sodium hydroxide solution
  2. additionwas added
  3. extractionthe mixture was extracted with chloroform
  4. washThe organic layer was washed with saturated brine
  5. customthe solvent was evaporated
  6. customThe obtained residue was purified by column chromatography

出典と根拠

ORDレコード
ord-0fdf4ae6063a4b78915839b4bb71f8be
出典データセット
uspto-grants-2014_08
特許番号
US08816079B2

反応ノート

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