Potassium Acetate → 3-(4-Chloro-1-methyl-1H-pyrazolo[3,4-b]pyridin-6-yl)-2-fluorobenzonitrile

HRID 241952Notes

Reaction equation

C([O-])(=O)C.[K+].[Cl:6][C:7]1[CH:12]=[C:11](Cl)[N:10]=[C:9]2[N:14]([CH3:17])[N:15]=[CH:16][C:8]=12.[C:18]([C:20]1[C:21]([F:29])=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=1)#[N:19]>CN(C=O)C.C(#N)C>[Cl:6][C:7]1[CH:12]=[C:11]([C:22]2[C:21]([F:29])=[C:20]([CH:25]=[CH:24][CH:23]=2)[C:18]#[N:19])[N:10]=[C:9]2[N:14]([CH3:17])[N:15]=[CH:16][C:8]=12

Participants

Conditions

Temperature: 125 °C

Procedure

Potassium acetate (4 mL, 1M, 4 mmol) was added to a mixture of 4,6-dichloro-1-methyl-1H-pyrazolo[3,4-b]pyridine 5 (0.115 g, 0.569 mmol), 3-cyano-2-fluorophenylboronic acid 14 (0.075 g, 0.455 mmol) in DMF (2 mL) and acetonitrile (2 mL). Nitrogen was bubbled through the mixture followed by the addition of 10 mole % tetrakis(triphenylphosphine) palladium (0) and the reaction was heated at 125° C. in a microwave for 20 minutes. Solvent was removed, and the residue was dissolved in ethyl acetate and washed with saturated sodium bicarbonate solution and brine (15 mL). The organic portions were pooled and dried over anhydrous sodium sulfate and the solvent was removed. The crude material was purified by reverse phase chromatography (Biotage) using ethyl acetate and hexanes as solvents to give 15 as white solid (0.035 g, 20%)

Workup

customNitrogen was bubbled through the mixture
additionfollowed by the addition of 10 mole % tetrakis(triphenylphosphine) palladium (0)
customSolvent was removed
dissolutionthe residue was dissolved in ethyl acetate
washwashed with saturated sodium bicarbonate solution and brine (15 mL)
dry with materialdried over anhydrous sodium sulfate
customthe solvent was removed
customThe crude material was purified by reverse phase chromatography (Biotage)

Sources & evidence

ORD record: ord-9f6b7c66911c44dab705ec8d75392eba
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653098B2

Reaction notes

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