Tetrahydrofuran → N-(5-bromo-4-methylpyridin-3-yl)tetrahydro-2H-pyran-4-carboxamide

HRID 468713

反応式

HRID 468713 の反応式
[Br:1][C:2]1[C:3]([CH3:9])=[C:4]([NH2:8])[CH:5]=[N:6][CH:7]=1.O1CCCC1.C[Mg]Br.[O:18]1[CH2:23][CH2:22][CH:21]([C:24](OC)=[O:25])[CH2:20][CH2:19]1>C1(C)C=CC=CC=1.ClCCl>[Br:1][C:2]1[C:3]([CH3:9])=[C:4]([NH:8][C:24]([CH:21]2[CH2:22][CH2:23][O:18][CH2:19][CH2:20]2)=[O:25])[CH:5]=[N:6][CH:7]=1

参加物

7

反応物 4

HCID 8028TetrahydrofuranHCID 27735202H-Pyran-4-carboxylic acid, tetrahydro-, methyl esterHCID 70606795-Bromo-4-methylpyridin-3-amineHCID 178418573HCID 178418573、化合物

生成物 1

HCID 67974771N-(5-bromo-4-methylpyridin-3-yl)tetrahydro-2H-pyran-4-carboxamide収率 26%

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

To a solution of 5-bromo-4-methylpyridin-3-amine (128.9 mg, 0.6892 mmol) in tetrahydrofuran (4.0 mL, 49 mmol) at 0° C. was added 1.4 M of methylmagnesium bromide in toluene (0.55 mL). After stirring at 0° C. for 10 minutes, methyl tetrahydro-2H-pyran-4-carboxylate (92.00 g, 638.1 mmol) was added. The reaction mixture was stirred overnight while warming to room temperature. The reaction mixture was poured into dichloromethane, washed with saturated aqueous NaHCO3, dried over MgSO4, and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (12 g silica, solvent gradient: 0-10% methanol in dichloromethane) to yield 53.5 mg (26%) of N-(5-bromo-4-methylpyridin-3-yl)tetrahydro-2H-pyran-4-carboxamide. LCMS (ESI): M+H=299.2.

後処理

  1. stirringThe reaction mixture was stirred overnight
  2. temperaturewhile warming to room temperature
  3. washwashed with saturated aqueous NaHCO3
  4. dry with materialdried over MgSO4
  5. customevaporated in vacuo
  6. customThe crude product was purified via flash chromatography on silica gel (12 g silica, solvent gradient: 0-10% methanol in dichloromethane)

出典と根拠

ORDレコード
ord-0d18ffedee634b008e7068232643a32e
出典データセット
uspto-grants-2014_01
特許番号
US08623889B2

関連ノート

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