Sodium hydride → (3-(3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)phenyl)(morpholino)methanone

HRID 1171094Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1171094
[I:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:11]3[CH:12]=[C:13]([C:17]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[O:18])[CH:14]=[CH:15][CH:16]=3)[CH:9]=2)[NH:4][N:3]=1.[H-].[Na+].[CH3:27][Si:28]([CH2:31][CH2:32][O:33][CH2:34]Cl)([CH3:30])[CH3:29]>CN(C=O)C>[I:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:11]3[CH:12]=[C:13]([C:17]([N:19]4[CH2:20][CH2:21][O:22][CH2:23][CH2:24]4)=[O:18])[CH:14]=[CH:15][CH:16]=3)[CH:9]=2)[N:4]([CH2:34][O:33][CH2:32][CH2:31][Si:28]([CH3:30])([CH3:29])[CH3:27])[N:3]=1.[N:19]1([C:17]([C:13]2[CH:14]=[CH:15][CH:16]=[C:11]([C:8]3[CH:7]=[N:6][C:5]4=[N:4][N:3]([CH2:34][O:33][CH2:32][CH2:31][Si:28]([CH3:30])([CH3:29])[CH3:27])[CH:2]=[C:10]4[CH:9]=3)[CH:12]=2)=[O:18])[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1

Komponenten

6

Edukt 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178519550HCID 178519550, Verbindung

Produkt 2

HCID 59836119(3-(3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)phenyl)(morpholino)methanoneHCID 68617900morpholin-4-yl-{3-[2-(2-trimethylsilanyl-ethoxymethyl)-2H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-methanone

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
2.5 °C

Versuchsvorschrift

To a solution of [3-(3-iodo-1H-pyrazolo[3,4-b]pyridin-5-yl)-phenyl]-morpholin-4-yl-methanone (2.12 g, 4.88 mmol) in anhydrous DMF (30 mL) was added sodium hydride (60% in mineral oil, 750 mg, 30 mmol) at 0-5° C. The mixture was stirred for a few minutes before trimethylsilylethoxymethyl chloride (2.0 ml, 11 mmol) was added drop wise at the same temperature. The mixture was stirred at 0° C. to room temperature for 4 hours and then cooled to 0-5° C. and quenched by an addition of methanol. The resulting suspension was then distributed between water, saturated aqueous ammonium chloride solution and ether. The aqueous phase was extracted three times with ether and the combined organic phases were dried over sodium sulfate, filtered and concentrated. The crude product was then purified by silica gel chromatography using a gradient of ethyl acetate in hexanes to afford {3-[3-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-morpholin-4-yl-methanone as a beige-brown foam (1.806 g, 66% by 1H-NMR, side product identified as morpholin-4-yl-{3-[2-(2-trimethylsilanyl-ethoxymethyl)-2H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-methanone). 1H-NMR (500 MHz, d6-DMSO) δ 9.08 (d, 1H), 8.29 (d, 1H), 8.01 (m, 1H), 7.95 (t, br, 1H], 7.69 (t, 1H), 7.55 (d, br, 1H), 5.88 (s, 2H), 3.71 (t, 2H), 3.85-3.45 (m, 8H), 0.94 (t, 2H), −0.2 (s, 9H). MS: m/z 565 [MNa+], 537 [MH+], 447 [MH+-(Me3 Si(CH2)2O)].

Aufarbeitung

  1. additionwas added drop wise at the same temperature
  2. customquenched by an addition of methanol
  3. extractionThe aqueous phase was extracted three times with ether
  4. dry with materialthe combined organic phases were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was then purified by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-f93a1f2826764fa394ec59e83a53b958
Quelldatensatz
uspto-grants-2010_11
Patentnummer
US07829558B2

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