Diisobutylaluminumhydride → [1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methanol

HRID 1675656Notes

Reaction equation

HRID 1675656 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:24][CH3:25])=[C:10]([C:19](OCC)=[O:20])[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].[H-].C([Al+]CC(C)C)C(C)C>ClCCl.C1(C)C=CC=CC=1>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:24][CH3:25])=[C:10]([CH2:19][OH:20])[C:11]([NH:12][CH:13]3[CH2:14][CH2:15][O:16][CH2:17][CH2:18]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2]

Participants

5

Reactant 2

HCID 21225700DiisobutylaluminumhydrideHCID 59683211Ethyl 1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate2×

Product 1

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

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of ethyl 1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate (17.94 g, 51.85 mmol, e.g. which can optionally be as prepared in Intermediate 4) in dichloromethane (150 ml) was cooled to 0° C. under an atmosphere of nitrogen, and was treated with di-iso-butylaluminum hydride (100 ml of a 1.5 M solution in toluene, 150 mmol) added dropwise over 30 minutes, keeping the temperature steady at 0° C. The reaction was stirred at 0° C. for a further 30 minutes after completion of the addition. The reaction was quenched by the dropwise addition of saturated aqueous potassium sodium tartrate solution (120 ml), keeping the temperature below 5° C. The resulting mixture was diluted with ethyl acetate (300 ml) and the whole filtered through a pad of Celite, to form two layers. During this filtration the sinter funnel imploded. Material spilt on the fumehood floor was soaked up and recovered as much as possible. The organic layer was separated and dried (MgSO4), the drying agent was filtered off, and the filtrate evaporated to give a first batch of product. The aqueous layer and the celite were extracted with a larger amount of ethyl acetate to give a second batch of product after evaporation. The two batches of product were combined to give the title compound (14 g) as an off-white waxy solid.

Workup

  1. additionadded dropwise over 30 minutes
  2. customsteady at 0° C
  3. additionafter completion of the addition
  4. customThe reaction was quenched by the dropwise addition of saturated aqueous potassium sodium tartrate solution (120 ml)
  5. customthe temperature below 5° C
  6. additionThe resulting mixture was diluted with ethyl acetate (300 ml)
  7. filtrationthe whole filtered through a pad of Celite
  8. customto form two layers
  9. filtrationDuring this filtration the sinter funnel
  10. customrecovered as much as possible
  11. customThe organic layer was separated
  12. dry with materialdried (MgSO4)
  13. filtrationthe drying agent was filtered off
  14. customthe filtrate evaporated
  15. customto give a first batch of product
  16. extractionThe aqueous layer and the celite were extracted with a larger amount of ethyl acetate
  17. customto give a second batch of product
  18. customafter evaporation

Sources & evidence

ORD record
ord-bc3e61a6885d4a95bfcdbe34c81bf0b6
Source dataset
uspto-grants-2011_08
Patent number
US08003663B2

Reaction notes

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