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

HRID 1675657Notes

Reaction equation

HRID 1675657 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].CO.[BH4-].[Li+].O>O1CCCC1>[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

6

Reactant 4

HCID 887Methanol3×HCID 962Water2×HCID 4148881Lithium borohydride2×HCID 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 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of ethyl 1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate (60.43 g, 174 mmol, 1 equivalent, e.g. which can optionally be as prepared in Intermediate 4) in dry tetrahydrofuran (300 ml) was added dry methanol (28.3 ml, 22.3 g, 698 mmol, 4 equivalents), followed by slow addition of lithium borohydride (LiBH4, 2 M solution in tetrahydrofuran, 262 ml, 523 mmol, 3 equivalents) over 30 minutes. The mixture was heated as the lithium borohydride was added, reaching reflux after about 20 minutes. Further aliquots of methanol (14.1 ml, 2 equivalents, each time) were added after 1 hour and again after 1.5 hours, and the heating was continued for a further 30 minutes (for 2 hours total). The reaction mixture was cooled (ice/water bath) and was carefully treated with methanol (100 ml, non-dried) followed by cautious addition of water (200 ml) which resulted in cloudiness and then a precipitate. Addition of more water (800 ml) produced a more homogenous suspension which was stirred for 1 hour and which was then extracted with dichloromethane (about 1.5 L total volume). The organic extracts were combined, were washed with water and then brine, and were dried and evaporated to give the title compound as a white solid (49.84 g). LCMS m/z 305 [MH+]; TRET=1.79 and 1.83 min (double peak).

Workup

  1. additionwas added
  2. temperaturereaching reflux after about 20 minutes
  3. custom(for 2 hours total)
  4. customresulted in cloudiness
  5. customproduced a more homogenous suspension which
  6. extractionwhich was then extracted with dichloromethane (about 1.5 L total volume)
  7. washwere washed with water
  8. dry with materialbrine, and were dried
  9. customevaporated

Sources & evidence

ORD record
ord-826cdf967ca44218b26dbafbc3b2187d
Source dataset
uspto-grants-2011_08
Patent number
US08003663B2

Reaction notes

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