Sodium Carbonate → 4-(2-(1H-pyrazol-4-yl)pyridin-4-yloxy)-3-fluoroaniline

HRID 450422Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][C:10]=2[F:16])[CH:5]=[CH:4][N:3]=1.CC1(C)C(C)(C)OB([C:25]2[CH:26]=[N:27][NH:28][CH:29]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1.C(O)C.O>[NH:27]1[CH:26]=[C:25]([C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][C:10]=3[F:16])[CH:5]=[CH:4][N:3]=2)[CH:29]=[N:28]1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 4-(2-chloropyridin-4-yloxy)-3-fluoroaniline (3.0 g, 12.6 mmol, from Example A2) in a solvent comprised of toluene/ethanol/water (4:4:1, 50 mL) was added 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (3.17 g, 16.4 mmol), sodium carbonate (4.01 g, 37.8 mmol) and tetrakis(triphenylphosphine)palladium (0.73 g, 0.63 mmol). The headspace was evacuated and back-filled with nitrogen (3×) and then the reaction mixture was heated to 100° C. overnight. The reaction was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether) to give 4-(2-(1H-pyrazol-4-yl)pyridin-4-yloxy)-3-fluoroaniline (2.66 g, 78% yield). 1H NMR (400 MHz, DMSO-d6): δ 13.03 (brs, 1H), 8.28-8.31 (m, 2H), 7.99 (s, 1H), 7.24 (s, 1H), 6.95-7.00 (m, 1H), 6.39-6.50 (m, 3H), 5.43 (brs, 2H); MS (ESI): m/z 271.1 [M+H]+.

Workup

customThe headspace was evacuated
additionback-filled with nitrogen (3×)
concentrationThe reaction was concentrated under reduced pressure
customthe residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether)

Sources & evidence

ORD record: ord-e89709b3dc2e4a34a7c9b35fef9ce66a
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08486951B2

Reaction notes

Loading…