6-Amino-3-chloropyridazine → 6-(2-Fluoro-4-(trifluoromethyl)phenyl)pyridazin-3-amine

HRID 1626440Notes

Reaction equation

Cl[C:2]1[N:7]=[N:6][C:5]([NH2:8])=[CH:4][CH:3]=1.[F:9][C:10]1[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:11]=1B(O)O.[F-].[Cs+].C(N(C(C)C)C(C)C)C>C(O)CC.CCOC(C)=O>[F:9][C:10]1[CH:15]=[C:14]([C:16]([F:17])([F:18])[F:19])[CH:13]=[CH:12][C:11]=1[C:2]1[N:7]=[N:6][C:5]([NH2:8])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 6-chloropyridazin-3-amine (0.300 g, 2.32 mmol), 2-fluoro-4-(trifluoromethyl)phenylboronic acid (0.626 g, 3.01 mmol), cesium fluoride (0.915 g, 6.02 mmol), and N-ethyl-N-isopropylpropan-2-amine (0.449 g, 3.47 mmol) in propanol (17 ml) degassed with argon was added (dppf)palladium(II) chloride dichloromethane adduct (0.0953 g, 0.116 mmol), and the reaction was heated to 100° C. in a sealed tube for 3 hours. The reaction was cooled to ambient temperature, diluted with EtOAc, and washed with water and saturated sodium chloride. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude material was purified by flash chromatography on silica gel, eluting with a linear gradient of 0-10% methanol/EtOAc to yield the desired compound (0.086 g, 0.334 mmol, 14.4% yield).

Workup

temperatureThe reaction was cooled to ambient temperature
washwashed with water and saturated sodium chloride
dry with materialThe organic layer was dried over anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe crude material was purified by flash chromatography on silica gel
washeluting with a linear gradient of 0-10% methanol/EtOAc

Sources & evidence

ORD record: ord-d2902e3fe8f74865b1a3efa3b8db0376
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08785445B2

Reaction notes

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