2,3-Difluorophenylacetic acid → HCID 178520266, compound

HRID 269519Notes

Reaction equation

HRID 269519 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][C:10]([OH:12])=O.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[NH:23]1[C:27]2=[N:28][CH:29]=[CH:30][CH:31]=[C:26]2[C:25](C(OCC)=O)=[N:24]1.N1C2=NC=CC=C2C(C(OC(C)C)=O)=N1>C1COCC1>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][C:10]([C:25]1[C:26]2[C:27](=[N:28][CH:29]=[CH:30][CH:31]=2)[NH:23][N:24]=1)=[O:12]

Participants

6

Reactant 4

HCID 5207722,3-Difluorophenylacetic acidHCID 2733832Lithium HexamethyldisilazideHCID 178459485HCID 178459485, compoundHCID 178470482Ethyl 1H-pyrazolo[3,4-b]pyridine-3-carboxylate

Product 1

HCID 178520266HCID 178520266, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 2,3-difluorophenylacetic acid (236 mg, 1.4 mmol) in THF at OC was added 3.85 mL (3.85 mmol) of a solution of lithium bis-trimethylsilylamide in THF. The resulting solution was then added to solution of a 2:1 mixture of ethyl 1H-pyrazolo[3,4-b]pyridine-3-carboxylate and isopropyl 1H-pyrazolo[3,4-b]pyridine-3-carboxylate (104 mg, 0.55 mmol) in THF. The resulting mixture was heated at 75C for 3 hours. The reaction progress was monitored by TLC and HPLC and quenched with saturated NH4Cl, diluted with EtOAc and washed with saturated NaHCO3 and brine. The organic layer was dried over MgSO4 and concentrated to give 137 mg (91% yield) of 2-(2,3-difluorophenyl)-1-(1H-pyrazolo[3,4-b]pyridin-3-yl)ethanone. LC-MS Rt=3.3 min ES+ (274.0) ES− (272.1).

Workup

  1. customquenched with saturated NH4Cl
  2. additiondiluted with EtOAc
  3. washwashed with saturated NaHCO3 and brine
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-7c485fca78ec40f4b6af520267262c41
Source dataset
uspto-grants-2008_11
Patent number
US07446199B2

Reaction notes

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