Cesium fluoride → 3-Bromo-N-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]imidazo[1,2-b]pyridazin-6-amine

HRID 2279072Notes

Reaction equation

[Br:1][C:2]1[N:6]2[N:7]=[C:8](Cl)[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[F:12][C:13]1[CH:14]=[N:15][C:16]([C@@H:19]([NH2:21])[CH3:20])=[N:17][CH:18]=1.[F-].[Cs+]>CS(C)=O>[Br:1][C:2]1[N:6]2[N:7]=[C:8]([NH:21][C@H:19]([C:16]3[N:17]=[CH:18][C:13]([F:12])=[CH:14][N:15]=3)[CH3:20])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1

Participants

Conditions

Temperature: 180 °C

Procedure

A mixture of 3-bromo-6-chloroimidazo[1,2-b]pyridazine (Preparation 1b, 0.2 g, 0.86 mmol), (1S)-1-(5-fluoropyrimidin-2-yl)ethanamine (prepared according to the method described in WO2006/82392A1, 0.24 g, 1.72 mmol), cesium fluoride (1.31 g, 8.60 mmol) and dimethylsulfoxide (5 mL) was heated at 180° C. for 2 hours in a sealed tube. The reaction was cooled down, filtered through Celite® eluting with ethyl acetate and the filtrate was washed with water, dried over magnesium sulphate and the solvent removed under reduced pressure. The residue was purified by flash chromatography (40-70% acetone in hexanes) to give the title compound (0.11 g, 64%) as a brown foam.

Workup

customprepared
temperatureThe reaction was cooled down
filtrationfiltered through Celite®
washeluting with ethyl acetate
washthe filtrate was washed with water
dry with materialdried over magnesium sulphate
customthe solvent removed under reduced pressure
customThe residue was purified by flash chromatography (40-70% acetone in hexanes)

Sources & evidence

ORD record: ord-928e98ec59834057bfd4880bf1bfd7e5
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133200B2

Reaction notes

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