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

HRID 1675658Notes

Reaction equation

HRID 1675658 reaction equation
S(Cl)(Cl)=O.[CH2:5]([N:7]1[C:11]2=[N:12][C:13]([CH2:25][CH3:26])=[C:14]([CH2:23]O)[C:15]([NH:16][CH:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[C:10]2[CH:9]=[N:8]1)[CH3:6].[N-:27]=[N+:28]=[N-:29].[Na+].C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.CS(C)=O.CO>[N:27]([CH2:23][C:14]1[C:13]([CH2:25][CH3:26])=[N:12][C:11]2[N:7]([CH2:5][CH3:6])[N:8]=[CH:9][C:10]=2[C:15]=1[NH:16][CH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1)=[N+:28]=[N-:29]

Participants

8

Reactant 4

HCID 24386Thionyl ChlorideHCID 33557Sodium AzideHCID 516892Sodium BicarbonateHCID 59683222[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methanol

Product 1

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

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

Thionyl chloride (SOCl2, 50.37 ml, 82.11 g, 69 mmol) was added dropwise over 15 minutes to a suspension of [1,6-d]ethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methanol (13.98 g, 46 mmol, e.g. which can optionally be as described in Intermediate 5) in toluene (140 ml) at room temperature. The mixture was then heated at reflux at about 85° C. for 4 hours, was allowed to cool, and then was evaporated to dryness and azeotroped with three further portions of toluene. The residue obtained was dissolved in dry dimethylsulfoxide (100 ml) and treated with sodium azide (4.49 g, 69 mmol), and the mixture was stirred at room temperature for 18 hours. The mixture was poured into saturated aqueous sodium bicarbonate solution and was extracted with 3 portions of ethyl acetate. The combined organic extracts were washed with saturated brine and water, and were then dried (Na2SO4), the drying agent was filtered off, and the filtrate was evaporated to dryness. The residue obtained was purified by flash chromatography, eluting with 1:1 cyclohexane:ethyl acetate. Fractions containing the product without substantial amounts of impurities were evaporated to give the title compound (5.6 g+4.75 g=10.35 g).

Workup

  1. customat room temperature
  2. temperatureThe mixture was then heated
  3. temperatureto cool
  4. customwas evaporated to dryness
  5. customazeotroped with three further portions of toluene
  6. customThe residue obtained
  7. extractionwas extracted with 3 portions of ethyl acetate
  8. washThe combined organic extracts were washed with saturated brine and water
  9. dry with materialwere then dried (Na2SO4)
  10. filtrationthe drying agent was filtered off
  11. customthe filtrate was evaporated to dryness
  12. customThe residue obtained
  13. customwas purified by flash chromatography
  14. washeluting with 1:1 cyclohexane
  15. additionFractions containing the product without substantial amounts of impurities
  16. customwere evaporated

Sources & evidence

ORD record
ord-4c9ce0cee75141169606cab24dd23653
Source dataset
uspto-grants-2011_08
Patent number
US08003663B2

Reaction notes

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