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

HRID 1675660Notes

Reaction equation

HRID 1675660 reaction equation
[N:1]([CH2:4][C:5]1[C:10]([CH2:11][CH3:12])=[N:9][C:8]2[N:13]([CH2:16][CH3:17])[N:14]=[CH:15][C:7]=2[C:6]=1[NH:18][CH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)=[N+]=[N-]>[Pd].C(O)C>[NH2:1][CH2:4][C:5]1[C:10]([CH2:11][CH3:12])=[N:9][C:8]2[N:13]([CH2:16][CH3:17])[N:14]=[CH:15][C:7]=2[C:6]=1[NH:18][CH:19]1[CH2:20][CH2:21][O:22][CH2:23][CH2:24]1

Participants

4

Reactant 1

HCID 596832325-(Azidomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine2×

Product 1

HCID 596832145-(Aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent2×

Procedure

In a hydrogenation flask, ethanol (300 ml) was added to 10% palladium on carbon (9.9 g, 0.2 wt. equivalents, 50% wet), followed by 5-(azidomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine (49.62 g, 151 mmol, 1 equivalent, e.g. which can be as prepared in Intermediate 6) in ethanol (900 ml). The mixture was hydrogenated overnight at room temperature and room pressure (using the Wright valve); during which the flask was vented and refilled once. The catalyst was removed by filtration and the filtrate was evaporated to give a grey solid. The residue was purified by column chromatography, using a relatively small amount of silica (1500 ml of 9385 silica), eluting initially with 5% methanol in dichloromethane (to elute some fast-moving impurities), followed by 10% and finally 15% methanol in dichloromethane to give the title compound as an almost white solid (41.25 g). LCMS m/z 304 [MH+]; TRET=1.65 and 1.69 min (split peak). NMR (d6-DMSO) showed a trace of methanol present in the product.

Workup

  1. additionrefilled once
  2. customThe catalyst was removed by filtration
  3. customthe filtrate was evaporated
  4. customto give a grey solid
  5. customThe residue was purified by column chromatography
  6. washeluting initially with 5% methanol in dichloromethane (
  7. washto elute some fast-moving impurities),

Sources & evidence

ORD record
ord-fd4ec49c638a445f8f9a4b63da1bc904
Source dataset
uspto-grants-2011_08
Patent number
US08003663B2

Reaction notes

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