Methyl iodide → 2-(4,6-difluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

HRID 246068노트

반응식

HRID 246068 반응식
[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[C:4]([C:12]1[N:13]=[C:14]3[C:20]([CH:21]=[O:22])=[CH:19][N:18]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[C:15]3=[N:16][CH:17]=1)=[N:5][NH:6]2.[H-].[Na+].I[CH3:34]>CN(C=O)C>[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[C:4]([C:12]1[N:13]=[C:14]3[C:20]([CH:21]=[O:22])=[CH:19][N:18]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[C:15]3=[N:16][CH:17]=1)=[N:5][N:6]2[CH3:34]

참가 물질

5

반응물 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 866779412-(4,6-difluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

생성물 1

HCID 866779422-(4,6-difluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde수율 24.3%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
0 °C

실험 절차

To a solution of 2-(4,6-difluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (890 mg, 2.1 mmol) in DMF (9 ml) at 0° C. was added sodium hydride (60% in mineral oil, 279 mg, 2.49 mmol). The reaction mixture was stirred at 0° C. for 10 min then iodomethane (0.18 ml, 2.9 mmol) was slowly added. The mixture was stirred at 0° C. for 30 min then at room temperature for 30 min. The reaction was quenched with sat'd NH4Cl, diluted with water and extracted with EtOAc (2×). The combined organics were washed with sat LiCl and brine then dried over MgSO4 and concentrated. The crude residue was purified by silica gel chromatography with 20% to 100% EtOAc/heptane to provide 226 mg (22%) of 2-(4,6-difluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde as a yellow solid.

후처리

  1. stirringThe mixture was stirred at 0° C. for 30 min
  2. waitat room temperature for 30 min
  3. customThe reaction was quenched with sat'd NH4Cl
  4. additiondiluted with water
  5. extractionextracted with EtOAc (2×)
  6. washThe combined organics were washed with sat LiCl and brine
  7. dry with materialthen dried over MgSO4
  8. concentrationconcentrated
  9. customThe crude residue was purified by silica gel chromatography with 20% to 100% EtOAc/heptane

출처 및 근거

ORD 기록
ord-ef354f6a626a4608a336bcc8d79d2d95
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

반응 노트

불러오는 중…