Water → HCID 14510255、化合物

HRID 477040ノート

反応式

HRID 477040 の反応式
[H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]([NH:11][C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)=[O:13])[CH:7]=[C:8]([F:10])[CH:9]=1.I[CH3:21].O>CN(C)C=O>[F:10][C:8]1[CH:7]=[C:6]([N:11]([CH3:21])[C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)=[O:13])[CH:5]=[C:4]([F:3])[CH:9]=1

参加物

6

反応物 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 14510254HCID 14510254、化合物

生成物 1

HCID 14510255HCID 14510255、化合物収率 56%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
65 °C

実験手順

To a suspension of 80% sodium hydride (1.22 g, 41 mmol) in anhydrous dimethylformamide (90 mL), was added dropwise a solution of N-(3,5-difluorophenyl)-2-pyridinecarboxamide, prepared by the process of Example 1, Step 1 (8.71 g, 37 mmol) in dimethylformamide (30 mL). The reaction mixture was warmed to 65° C. for 1 hour and then treated with iodomethane (2.60 mL, 42 mmol) at room temperature. After 2.5 hours the reaction mixture was poured into water (500 mL) and extracted with ethyl acetate (2×300 mL). The combined organic layers were washed with 75% brine, dried, preabsorbed onto silica gel, and flash chromatographed (300 g, elution with 40% ethyl acetate in petroleum ether) to yield pure N-(3,5-difluorophenyl)-N-methyl-2-pyridinecarboxamide (5.16 g, 21 mmol, 56%, m.p. 102°-104° C.), which was reacted with Lawesson's reagent (4.36 g, 11 mmol) in anhydrous toluene (65 mL) at reflux temperature for 1.5 hours. The toluene was evaporated and the residue was dissolved in dichloromethane, preadsorbed onto silica gel, flash chromatographed (300 g, elution with 10% ethyl acetate in petroleum ether), and recrystallized from ethyl acetate in petroleum ether to afford a yellow solid (2.36 g, 24%), m.p. 131°-134° C.

後処理

  1. extractionextracted with ethyl acetate (2×300 mL)
  2. washThe combined organic layers were washed with 75% brine
  3. customdried
  4. custompreabsorbed onto silica gel, and flash
  5. customchromatographed
  6. wash(300 g, elution with 40% ethyl acetate in petroleum ether)

出典と根拠

ORDレコード
ord-eda4a2590c514f0e851a901a235fe779
出典データセット
uspto-grants-1989_12
特許番号
US04886821

反応ノート

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