Cesium carbonate → 7-chloro-2-(difluoromethyl)-2H-pyrazolo[3,4-c]pyridine

HRID 930478Notes

Reaction equation

[Cl:1][C:2]1[N:3]=[CH:4][CH:5]=[C:6]2[CH:10]=[N:9][NH:8][C:7]=12.Cl[C:12]([F:17])([F:16])C([O-])=O.[Na+].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[Cl:1][C:2]1[C:7]2=[N:8][N:9]([CH:12]([F:17])[F:16])[CH:10]=[C:6]2[CH:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 95 °C

Procedure

A mixture of 7-chloro-1H-pyrazolo[3,4-c]pyridine (4.99 g, 32.5 mmol), sodium chlorodifluoroacetate (14.86 g, 97 mmol), and cesium carbonate (40.2 g, 123 mmol) in DMF (81 ml) was heated at 95° C. for 4 h. The reaction was allowed to cool to rt and the solids were filtered. The filtrate was diluted with water and extracted with EtOAc. The organic extract was washed with water, satd NaCl, dried over MgSO4, filtered and concentrated in vacuo. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage SNAP HP-silica gel column (100 g), eluting with a gradient of 5% to 60% EtOAc in hexane, to provide a white solid (1.4117 g, 6.93 mmol, 21.34% yield). MS m/z=203.9 [M+H]+. Calculated for C7H4ClF2N3: 203.

Workup

temperatureto cool to rt
filtrationthe solids were filtered
additionThe filtrate was diluted with water
extractionextracted with EtOAc
extractionThe organic extract
washwas washed with water
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customchromatographed through a Biotage SNAP HP-silica gel column (100 g)
washeluting with a gradient of 5% to 60% EtOAc in hexane

Sources & evidence

ORD record: ord-4ca554dc963e4db29d430d247b0bde85
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296734B2

Reaction notes

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