Cesium carbonate → 2-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

HRID 246074노트

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HRID 246074 반응식
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:12]=[C:13]4[C:19]([CH:20]=[O:21])=[CH:18][N:17]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:14]4=[N:15][CH:16]=3)=[N:7][NH:8]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].I[CH:37]1[CH2:40][O:39][CH2:38]1>CN(C=O)C>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:12]=[C:13]4[C:19]([CH:20]=[O:21])=[CH:18][N:17]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:14]4=[N:15][CH:16]=3)=[N:7][N:8]2[CH:37]2[CH2:40][O:39][CH2:38]2)=[CH:4][CH:3]=1

참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 133566863-IodooxetaneHCID 866779442-(6-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

생성물 1

HCID 866779432-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde수율 86.4%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
100 °C

실험 절차

In a microwave vial 2-(6-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (300 mg, 0.73 mmol) was dissolved in DMF (5 ml) and cesium carbonate (714 mg, 2.19 mmol) and 3-iodooxetane (200 mg, 1.08 mmol) were added. The vial was sealed and heated at 100° C. under microwave irradiation for 2 h. The reaction was cooled, quenched 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 295 mg (86%) of 2-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde as a white solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 10.48 (s, 1H), 9.40 (s, 1H), 8.86 (dd, J=9.1, 5.3 Hz, 1H), 8.31 (s, 1H), 7.11-7.25 (m, 2H), 5.72-5.86 (m, 3H), 5.41 (t, J=6.6 Hz, 2H), 5.20 (t, J=7.4 Hz, 2H), 3.56-3.70 (m, 2H), 0.85-1.06 (m, 2H), −0.02 (s, 9H).

후처리

  1. customThe vial was sealed
  2. temperatureThe reaction was cooled
  3. customquenched with water
  4. extractionextracted with EtOAc (2×)
  5. washThe combined organics were washed with sat LiCl and brine
  6. dry with materialthen dried over MgSO4
  7. concentrationconcentrated
  8. customThe crude residue was purified by silica gel chromatography with 20% to 100% EtOAc/heptane

출처 및 근거

ORD 기록
ord-ca819179d27f4ac4b59a1dcc0a92f6e0
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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