Water → 5-(3,5-difluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-amine

HRID 1487392Notes

Reaction equation

C(Cl)Cl.[Cl-].[F:5][C:6]1[CH:7]=[C:8]([CH:11]=[C:12]([F:14])[CH:13]=1)[CH2:9][Zn+].Br[C:16]1[CH:17]=[C:18]2[C:24]([NH2:25])=[N:23][NH:22][C:19]2=[N:20][CH:21]=1.O>O1CCCC1>[F:5][C:6]1[CH:7]=[C:8]([CH:11]=[C:12]([F:14])[CH:13]=1)[CH2:9][C:16]1[CH:17]=[C:18]2[C:24]([NH2:25])=[N:23][NH:22][C:19]2=[N:20][CH:21]=1

Participants

Conditions

Temperature: 90 °C

Procedure

CH2Cl2 and 28 ml (14.08 mmol) of 3,5-difluorobenzyl zinc (II) chloride are added to 1.5 g (7.04 mmol) of a solution of 5-bromo-1H-pyrazolo[3,4-b]pyridin-3-amine in 10 ml of tetrahydrofuran. The reaction medium is heated at 90° C. for 18 hours. After returning to room temperature, the reaction is hydrolyzed by slowly adding water at 0° C. After filtration of the precipitate formed, the solid is rinsed with tetrahydrofuran and the aqueous filtrate is extracted several times with ethyl acetate. The organic phases are combined, dried on magnesium sulfate and concentrated. The residue is purified by silica chromatography (95:4.5:0.5 and then 95:4:1 dichloromethane/methanol/ammonium as eluent) to yield 1.7 g (93%) of 5-(3,5-difluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-amine in the form of a beige solid.

Workup

customAfter returning to room temperature
filtrationAfter filtration of the precipitate
customformed
washthe solid is rinsed with tetrahydrofuran
extractionthe aqueous filtrate is extracted several times with ethyl acetate
customdried on magnesium sulfate
concentrationconcentrated
customThe residue is purified by silica chromatography (95:4.5:0.5

Sources & evidence

ORD record: ord-50225b10c7ca41338c863a46c2d38895
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09428510B2

Reaction notes

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