Sodium Hydroxide → 6-(4-fluorophenyl)-5-(2-methylsulfanylpyrimidin-4-yl)-1H-pyrazolo[3,4-b]pyridine

HRID 42606

Reaction equation

N[C:2]1[C:10]2[C:5](=[N:6][C:7]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)=[C:8]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([S:17][CH3:18])[N:12]=3)[CH:9]=2)[NH:4][N:3]=1.N([O-])=O.[Na+].O[PH2]=O.[OH-].[Na+]>CC(O)=O.O.Cl>[F:25][C:22]1[CH:23]=[CH:24][C:19]([C:7]2[N:6]=[C:5]3[NH:4][N:3]=[CH:2][C:10]3=[CH:9][C:8]=2[C:11]2[CH:16]=[CH:15][N:14]=[C:13]([S:17][CH3:18])[N:12]=2)=[CH:20][CH:21]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 3-amino-6-(4-fluorophenyl)-5-(2-methylsulfanylpyrimidin-4-yl)-1H-pyrazolo[3,4-b]pyridine (10.00 g, 28.4 mmol, obtained in example 180) in AcOH (52 mL), water (22 mL) and HCl conc. (5.7 mL), cooled to 0° C., a solution of NaNO2 (2.30 g, 33.4 mmol) in water (7.5 mL) was added dropwise. It was stirred for 30 min at 0° C., and H3PO2 (50% aqueous solution, 56.8 mL) was added slowly. It was stirred at 0° C. for 6 h. It was allowed to cool to room temperature, basified at 0° C. by slow addition of 6 N NaOH hasta pH=8 and was extracted with EtOAc. The combined organic phases were dried over Na2SO4 and concentrated to dryness. The crude product obtained was purified by chromatography on silica gel using hexane-EtOAc mixtures of increasing polarity as eluent, to afford 4.00 g of the title compound (yield: 42%)

Workup

stirringIt was stirred at 0° C. for 6 h
temperatureto cool to room temperature
extractionwas extracted with EtOAc
dry with materialThe combined organic phases were dried over Na2SO4
concentrationconcentrated to dryness
customThe crude product obtained
customwas purified by chromatography on silica gel
temperatureof increasing polarity as eluent

Sources & evidence

ORD record: ord-36bc6544a1ae40ee983059e6b2d908c5
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08536194B2

Linked notes

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