Sodium hydride → 5-bromo-3-iodo-1-(2-methoxy-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine

HRID 1171110Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1171110
[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([I:11])=[N:9][NH:8][C:5]2=[N:6][CH:7]=1.[H-].[Na+].[CH3:14][O:15][CH2:16][CH2:17][O:18][CH2:19]Cl.BrC1C=C2C(I)N(COCCOC)NC2=NC=1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([I:11])=[N:9][N:8]([CH2:14][O:15][CH2:16][CH2:17][O:18][CH3:19])[C:5]2=[N:6][CH:7]=1

Komponenten

7

Edukt 4

HCID 24758Sodium hydrideHCID 775901-(Chloromethoxy)-2-methoxyethaneHCID 686171755-bromo-3-iodo-2-(2-methoxy-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridineHCID 178419453HCID 178419453, Verbindung

Produkt 1

HCID 598361435-bromo-3-iodo-1-(2-methoxy-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridineAusbeute 74 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 67553Tetrabutylammonium IodideKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 5-bromo-3-iodo-1H-pyrazolo[3,4-b]pyridine (470 mg, 1.45 mmol), 60% sodium hydride in mineral oil (104 mg, 4.35 mmol) and tetra-n-butylammonium iodide (134 mg, 0.36 mmol) in DMF (10 mL) was added methoxyethoxymethyl chloride (248 μl, 2.18 mmol) at room temperature and the mixture was stirred for 4 h at the same temperature and subsequently quenched by addition of methanol. The mixture was then distributed between ether and brine and the organic layer dried over sodium sulfate, filtered and concentrated. The crude product was purified by flash silica gel chromatography using a gradient of ethyl acetate in hexanes to afford 5-bromo-3-iodo-1-(2-methoxy-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine (254 mg, 0.69 mmol, 74% yield) as a colorless solid (1:1 mixture with regioisomer 5-bromo-3-iodo-2-(2-methoxy-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine). 1H-NMR (500 MHz, d6-DMSO) isomer A (50%) S8.75 (d, 1H), 8.29 (d, 1H), 5.78 (s, 1H), 3.61-3.63 (m, 2H), 3.37-3.39 (m, 2H), 3.17 (s, 3H); isomer B (50%) δ 8.74 (d, 1H), 8.28 (d, 1H), 5.77 (s, 1H), 3.61-3.63 (m, 2H), 3.37-3.39 (m, 2H), 3.16 (s, 3H).

Aufarbeitung

  1. customsubsequently quenched by addition of methanol
  2. dry with materialthe organic layer dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified by flash silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-f8314698858f491cba3d6a9bb512a7d4
Quelldatensatz
uspto-grants-2010_11
Patentnummer
US07829558B2

Notizen zur Reaktion

Wird geladen…