Potassium Phosphate, Tribasic → 3,5-difluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)aniline

HRID 2060683Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:15]([F:16])=[CH:14][C:12]([NH2:13])=[CH:11][C:10]=2[F:17])[CH:5]=[CH:4][N:3]=1.[CH3:18][N:19]1[CH:23]=[C:22](B2OC(C)(C)C(C)(C)O2)[CH:21]=[N:20]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C=O.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:17][C:10]1[CH:11]=[C:12]([CH:14]=[C:15]([F:16])[C:9]=1[O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([C:22]2[CH:21]=[N:20][N:19]([CH3:18])[CH:23]=2)[CH:7]=1)[NH2:13]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 4-(2-chloropyridin-4-yloxy)-3,5-difluoroaniline (3.0 g, 11.7 mmol) in a mixture of N,N-dimethyl-formamide and water (v/v=3:1, 80 mL) was added 1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (3.6 g, 17.5 mmol), potassium phosphate (4.9 g, 23.4 mmol) and tetrakis(triphenylphosphine) palladium (0.7 g, 0.6 mmol). The mixture was degassed thoroughly, heated to 100° C. and stirred under nitrogen overnight. The solvent was removed under reduced pressure and the residue was purified by silica gel chromatography to give 3,5-difluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)aniline (2.6 g, 74% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.36 (d, J=5.6 Hz, 1H), 8.28 (s, 1H), 7.98 (s, 1H), 7.24 (d, J=2.4 Hz, 1H), 6.64 (dd, J=5.6 Hz, J=2.4 Hz, 1H), 6.37 (d, J=10.8 Hz, 2H), 5.81 (s, 2H), 3.87 (s, 3H); MS (ESI): m/z 303.1 [M+H]+.

Workup

customThe mixture was degassed thoroughly
customThe solvent was removed under reduced pressure
customthe residue was purified by silica gel chromatography

Sources & evidence

ORD record: ord-047fa001e2cc42d1af9728571c76a981
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08278331B2

Reaction notes

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