1-Benzyl-3-(4,6-dimethylpyridin-2-ylamino)pyrrolidine → 3-(4,6-Dimethylpyridin-2-ylamino)pyrrolidine

HRID 1666615

反応式

HRID 1666615 の反応式
C([N:8]1[CH2:12][CH2:11][CH:10]([NH:13][C:14]2[CH:19]=[C:18]([CH3:20])[CH:17]=[C:16]([CH3:21])[N:15]=2)[CH2:9]1)C1C=CC=CC=1>CO.[OH-].[OH-].[Pd+2]>[CH3:20][C:18]1[CH:17]=[C:16]([CH3:21])[N:15]=[C:14]([NH:13][CH:10]2[CH2:11][CH2:12][NH:8][CH2:9]2)[CH:19]=1

参加物

4

反応物 1

HCID 579702011-Benzyl-3-(4,6-dimethylpyridin-2-ylamino)pyrrolidine

生成物 1

HCID 579701123-(4,6-Dimethylpyridin-2-ylamino)pyrrolidine収率 11.3%

試薬・触媒・溶媒 2

HCID 9942167Palladium hydroxide触媒HCID 887Methanol溶媒

実験手順

A mixture of 2-amino-4,6-dimethylpyridine (2.0 g), 1-benzylpyrrolidin-3-one (2.9 g), acetic acid (2.9 mL), and chloroform (34 mL) was ice-cooled, followed by addition of sodium triacetoxyborohydride (4.9 g), and the mixture was stirred for 18 h while heating slowly to room temperature. To the reaction mixture was added 1 M aqueous sodium hydroxide to make it basic, and then the mixture was extracted with chloroform. The organic layer was dried with anhydrous magnesium sulfate, then the desiccant was removed by filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (NH silica gel, hexane/ethyl acetate=65:35) to obtain 1-benzyl-3-(4,6-dimethylpyridin-2-ylamino)pyrrolidine (1.3 g). (2) 1-Benzyl-3-(4,6-dimethylpyridin-2-ylamino)pyrrolidine (1.3 g) was dissolved in methanol (13 mL), followed by addition of 20% Pd(OH)2/C (0.26 g), and the mixture was stirred at room temperature for 20 h under hydrogen atmosphere. The catalyst was removed by Celite filtration, then the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (NH silica gel, chloroform/methanol=19:1) to obtain 3-(4,6-dimethylpyridin-2-ylamino)pyrrolidine (0.10 g). (3) A mixture solution of 3-(4,6-dimethylpyridin-2-ylamino)pyrrolidine (0.73 g), 4-trifluoromethoxyphenylacetic acid (0.12 g), EDC.HCl (0.12 g), HOBt.H2O (0.12 g), and chloroform (1.0 mL) was stirred at room temperature. After completion of the reaction, the reaction mixture was diluted with chloroform and washed with 1 M aqueous sodium hydroxide and brine. The organic layer was dried with anhydrous magnesium sulfate, then the desiccant was removed by filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform/methanol=19:1) and then crystallized with hexane and diethyl ether to obtain the title compound (0.14 g).

後処理

  1. customThe catalyst was removed by Celite filtration
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customthe residue was purified by silica gel column chromatography (NH silica gel, chloroform/methanol=19:1)

出典と根拠

ORDレコード
ord-828293e52094436693e59727ecf55099
出典データセット
uspto-grants-2011_10
特許番号
US08044068B2

関連ノート

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