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

HRID 564431Notes

Reaction equation

HRID 564431 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>C1COCC1>[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 887Methanol4×HCID 962WaterHCID 4148881Lithium borohydrideHCID 59683211Ethyl 1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate

Product 1

HCID 59683222[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methanolYield 94.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To ethyl 1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate (60.43 g, 174 mmol) in dry THF (300 mL) was added dry methanol (28.3 mL) followed by the addition of lithium borohydride (2M in THF, 262 mL, 523 mmol) over 30 min. The mixture was heated to reflux. After 1 h additional methanol (14.1 mL) was added. After a further 30 min additional methanol (14.1 mL) was added. After a further 30 min the mixture was cooled in an ice bath and treated with methanol (100 mL) followed (cautiously) with water (1000 mL). The mixture was stirred for 1 h and then extracted with dichloromethane (1,500 mL total). The combined organics were washed with water, then brine, dried and concentrated to dryness to afford 49.84 g of the title compound. LC-MS m/z 305 (M+H)+, 1.79 min (ret time).

Workup

  1. temperatureThe mixture was heated to reflux
  2. temperatureAfter a further 30 min the mixture was cooled in an ice bath
  3. extractionextracted with dichloromethane (1,500 mL total)
  4. washThe combined organics were washed with water
  5. dry with materialbrine, dried
  6. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-5002cc2a6e71437f8a6c84465fee415e
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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