Potassium Carbonate → 2,5-difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamine

HRID 2060715Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:14]([F:15])=[CH:13][C:12]([NH2:16])=[C:11]([F:17])[CH:10]=1.[CH3:18][N:19]1[CH:23]=[C:22](B2OC(C)(C)C(C)(C)O2)[CH:21]=[N:20]1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[F:17][C:11]1[CH:10]=[C:9]([O:8][C:7]2[CH:6]=[CH:5][N:4]=[CH:3][C:2]=2[C:22]2[CH:21]=[N:20][N:19]([CH3:18])[CH:23]=2)[C:14]([F:15])=[CH:13][C:12]=1[NH2:16]

Participants

Conditions

Temperature: 90 °C

Procedure

In a sealed tube, 4-(3-bromopyridin-4-yloxy)-2,5-difluorobenzenamine (0.42 g, 1.395 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.363 g, 1.744 mmol), potassium carbonate (0.578 g, 4.18 mmol), and tetrakistriphenylphosphine palladium (0) (0.081 g, 0.070 mmol) were suspended in dioxane (8 ml) and water (1.333 ml). The mixture was degassed with Ar and heated at 90° C. overnight. The reaction mixture was cooled and partitioned between EtOAc and sat. NaHCO3 (aq). The mixture was extracted with EtOAc (3×). The combined organic extracts were dried, evaporated and purified by silica gel chromatography (hexanes/EtOAc) to yield 2,5-difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamine (272 mg, 65% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.80 (s, 1H) 8.22-8.20 (m, 2H), 8.00 (s, 1H), 7.24-7.19 (m, 1H), 6.76-6.71 (m, 1H), 6.62 (d, 1H), 5.50 (br s, 2H), 3.78 (s, 3H); MS (ESI) m/z: 301.0 (M+H+).

Workup

customThe mixture was degassed with Ar
temperatureThe reaction mixture was cooled
custompartitioned between EtOAc and sat. NaHCO3 (aq)
extractionThe mixture was extracted with EtOAc (3×)
customThe combined organic extracts were dried
customevaporated
custompurified by silica gel chromatography (hexanes/EtOAc)

Sources & evidence

ORD record: ord-05f8f8d286b7482d97c9e55024966cad
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08278331B2

Reaction notes

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