Acetic Acid → HCID 52916889, compound

HRID 2172974Notes

Reaction equation

HRID 2172974 reaction equation
C[O:2][C:3](=[O:32])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]2([NH:13][C:14]([C:16]3[C:17]4[CH:24]=[N:23][N:22]([C:25]5[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=5)[C:18]=4[CH:19]=[N:20][CH:21]=3)=[O:15])[CH2:12][CH2:11]2)[CH:5]=1.O[Li].O.C(O)(=O)C>C1COCC1.CO.O>[F:31][C:28]1[CH:27]=[CH:26][C:25]([N:22]2[C:18]3[CH:19]=[N:20][CH:21]=[C:16]([C:14]([NH:13][C:10]4([C:6]5[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=5)[C:3]([OH:32])=[O:2])[CH2:12][CH2:11]4)=[O:15])[C:17]=3[CH:24]=[N:23]2)=[CH:30][CH:29]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 168937Lithium hydroxide, monohydrateHCID 52916888HCID 52916888, compound

Product 1

HCID 52916889HCID 52916889, compound

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

To a solution of 3-(1-{[1-(4-fluoro-phenyl)-1H-pyrazolo[3,4-c]pyridine-4-carbonyl]-amino}-cyclopropyl)-benzoic acid methyl ester (0.650 g, 1.51 mmol) in a mixture of THF/methanol/water (22.5 mL, 3:1:1) is added LiOH.H2O (253 mg, 6.04 mmol). After 3 hours, the reaction mixture is neutralized with glacial acetic acid and concentrated in vacuo. The residue is dissolved in a solution of 20% methanol in methylene chloride (100 mL). Water (100 mL) is added and the mixture is acidified to pH 4 with 2M aqueous hydrochloric acid. Phases are separated, and the aqueous layer is extracted with 20% methanol in methylene chloride (9×100 mL). The combined organic layers are dried over MgSO4, filtered and concentrated to approximately 50 mL. The resulting crystallized solids are filtered, washed with cold methanol (3×2 mL) and air dried to afford the title compound as a solid.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue is dissolved in a solution of 20% methanol in methylene chloride (100 mL)
  3. additionWater (100 mL) is added
  4. customPhases are separated
  5. extractionthe aqueous layer is extracted with 20% methanol in methylene chloride (9×100 mL)
  6. dry with materialThe combined organic layers are dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated to approximately 50 mL
  9. customThe resulting crystallized solids
  10. filtrationare filtered
  11. washwashed with cold methanol (3×2 mL) and air
  12. customdried

Sources & evidence

ORD record
ord-7072b10281024010966032831b37d896
Source dataset
uspto-grants-2015_06
Patent number
US09056858B2

Reaction notes

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