Sodium Azide → 5-(Azidomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine

HRID 564432

Reaktionsgleichung

Reaktionsgleichung von HRID 564432
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:21][CH3:22])=[C:10]([CH2:19]O)[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2].[N-:23]=[N+:24]=[N-:25].[Na+]>CS(C)=O.S(Cl)(Cl)=O>[N:23]([CH2:19][C:10]1[C:9]([CH2:21][CH3:22])=[N:8][C:7]2[N:3]([CH2:1][CH3:2])[N:4]=[CH:5][C:6]=2[C:11]=1[NH:12][CH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1)=[N+:24]=[N-:25]

Komponenten

5

Edukt 2

HCID 33557Sodium AzideHCID 59683222[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methanol

Produkt 1

HCID 596832325-(Azidomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amineAusbeute 218,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24386Thionyl ChlorideKatalysatorHCID 679Dimethyl SulfoxideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To [1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methanol (24.9 g, 82 mmol) was added thionyl chloride (90 mL, 1.23 mmol) and the mixture was heated to 80° C. under an atmosphere of nitrogen. After 2 h the mixture was cooled, concentrated and the residue azeotroped with toluene. The residue was then dissolved in a solution of sodium azide (7.98 g, 123 mmol) in DMSO (120 mL). The mixture was stirred for 16 h. The above procedure was repeated on the same scale and the 2 reactions combined for work-up. The combined DMSO mixture was partitioned between ethyl acetate and aqueous sodium bicarbonate. The aqueous phase was extracted thoroughly with ethyl acetate and the combined organics were washed with water, then brine, dried and concentrated to afford 58.9 g of a brown solid. The product was purified by flash chromatography on 1.5 kg of silica using a step gradient from 3:1 to 2:1 cyclohexane/ethyl acetate to afford 39.94 g of the title compound. LC-MS m/z 330 (M+H)+, 2.21 min (ret time).

Aufarbeitung

  1. temperatureAfter 2 h the mixture was cooled
  2. concentrationconcentrated
  3. customthe residue azeotroped with toluene
  4. customThe combined DMSO mixture was partitioned between ethyl acetate and aqueous sodium bicarbonate
  5. extractionThe aqueous phase was extracted thoroughly with ethyl acetate
  6. washthe combined organics were washed with water
  7. dry with materialbrine, dried
  8. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-cb14ebfd6ab0473faa3a31bd4f339675
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08067408B2

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