Ibudilast → 1-(2-Isopropyl-pyrazolo[1,5-a]pyridin-3-yl)-2-methyl-propan-1-ol

HRID 731711Notes

Reaction equation

HRID 731711 reaction equation
[CH:1]([C:4]1[C:12]([C:13](=[O:17])[CH:14]([CH3:16])[CH3:15])=[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][N:6]2[N:5]=1)([CH3:3])[CH3:2].[BH4-].[Na+]>CO>[CH:1]([C:4]1[C:12]([CH:13]([OH:17])[CH:14]([CH3:16])[CH3:15])=[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][N:6]2[N:5]=1)([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 3671IbudilastHCID 4311764Sodium borohydride

Product 1

HCID 133917031-(2-Isopropyl-pyrazolo[1,5-a]pyridin-3-yl)-2-methyl-propan-1-olYield 68%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

2.5 g (10.76 mmol) of 1-(2-isopropylpyrazolo[1,5-a]pyridin-3-yl)-2-methylpropan-1-one was dissolved in MeOH (50 ml) (charcoal filtration) and cooled to 0° C. NaBH4 (570 mg, 15.06 mmol) was added portion wise. The reaction mixture was heated to reflux until complete conversion of starting material (2-4 hours). The reaction mixture was cooled to room temperature, and was quenched by the addition of water (50 ml). The aqueous layer was extracted four times with dichloromethane. The combined organic layers were washed with brine, treated with charcoal, dried over Na2SO4, and the solvent was evaporated under reduced pressure. Flash column chromatography (hexanes-ethyl acetate, 5:2; 10% deactivated silica) of the residue (yellow oil) afforded 1-(2-isopropylpyrazolo[1,5-a]pyridin-3-yl)-2-methylpropan-1-ol as a colorless oil (1.7 g, 68%), which crystallized upon trituration with pentane; m.p. 69° C. Compound 1002.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux until complete conversion of starting material (2-4 hours)
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customwas quenched by the addition of water (50 ml)
  5. extractionThe aqueous layer was extracted four times with dichloromethane
  6. washThe combined organic layers were washed with brine
  7. additiontreated with charcoal
  8. dry with materialdried over Na2SO4
  9. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-934837c24b2f498cba45ecf3e8a26831
Source dataset
uspto-grants-2009_09
Patent number
US07585875B2

Reaction notes

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