Diisopropylamine → 1-(3-Fluorophenyl)-4-hydroxy-7-methyl-1H-pyrazolo[3,4-b]pyridin-6(7H)-one

HRID 659707Notes

Reaction equation

HRID 659707 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[Li+].CC([N-]C(C)C)C.[F:21][C:22]1[CH:23]=[C:24]([N:28]2[C:32]([N:33]([CH3:37])[C:34](=[O:36])[CH3:35])=[C:31]([C:38]([O:40]CC)=O)[CH:30]=[N:29]2)[CH:25]=[CH:26][CH:27]=1>C1COCC1>[F:21][C:22]1[CH:23]=[C:24]([N:28]2[C:32]3[N:33]([CH3:37])[C:34](=[O:36])[CH:35]=[C:38]([OH:40])[C:31]=3[CH:30]=[N:29]2)[CH:25]=[CH:26][CH:27]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 2724682Lithium diisopropylamideHCID 57708074ethyl 1-(3-fluorophenyl)-5-(N-methylacetamido)-1H-pyrazole-4-carboxylateHCID 178418339Butyllithium

Product 1

HCID 577080711-(3-Fluorophenyl)-4-hydroxy-7-methyl-1H-pyrazolo[3,4-b]pyridin-6(7H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of diisopropylamine (3.45 mL, 24.4 mmol) in 15 mL THF under argon at 0° C. was treated with n-butyllithium (14.7 mL of 1.6 M solution in hexanes, 23.5 mmol) and stirred at this temperature for 30 min. The freshly prepared LDA was added dropwise to a solution of ethyl 1-(3-fluorophenyl)-5-(N-methylacetamido)-1H-pyrazole-4-carboxylate (2.87 g, 9.40 mmol) in 5 mL of THF at −78° C. After the reaction mixture was gradually warmed to RT in 4 h, it was partitioned between 1N NaOH and 45 mL of ether. The ether layer was separated and discarded; the aqueous layer was acidified with 2 N HCl, and extracted three times with EtOAc. The combined EtOAc layers were washed with brine, dried over MgSO4, and concentrated to yield the title compound as a tan crystalline solid. MS (ESI, pos.ion) m/z: 260.1 (M+1). The crude material was used in the next step without further purification.

Workup

  1. customit was partitioned between 1N NaOH and 45 mL of ether
  2. customThe ether layer was separated
  3. extractionextracted three times with EtOAc
  4. washThe combined EtOAc layers were washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-04ea24acbaf141ef8383baa80c56d54e
Source dataset
uspto-grants-2011_12
Patent number
US08080546B2

Reaction notes

Loading…