Water → HCID 14510255, 화합물

HRID 477040노트

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HRID 477040 반응식
[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

참가 물질

6

반응물 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 14510254HCID 14510254, 화합물

생성물 1

HCID 14510255HCID 14510255, 화합물수율 56%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

반응 조건

온도
65 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-eda4a2590c514f0e851a901a235fe779
출처 데이터셋
uspto-grants-1989_12
특허 번호
US04886821

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