4-Fluorophenol → 6-amino-5-bromo-2-(6-(4-fluorophenoxy)pyridin-3-yl)-N-methylbenzofuran-3-carboxamide

HRID 595563Notes

Reaction equation

[NH2:1][C:2]1[C:21]([Br:22])=[CH:20][C:5]2[C:6]([C:16]([NH:18][CH3:19])=[O:17])=[C:7]([C:9]3[CH:10]=[N:11][C:12](F)=[CH:13][CH:14]=3)[O:8][C:4]=2[CH:3]=1.[F:23][C:24]1[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C1COCC1>[NH2:1][C:2]1[C:21]([Br:22])=[CH:20][C:5]2[C:6]([C:16]([NH:18][CH3:19])=[O:17])=[C:7]([C:9]3[CH:10]=[N:11][C:12]([O:30][C:27]4[CH:28]=[CH:29][C:24]([F:23])=[CH:25][CH:26]=4)=[CH:13][CH:14]=3)[O:8][C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a degassed solution of 6-amino-5-bromo-2-(6-fluoropyridin-3-yl)-N-methylbenzofuran-3-carboxamide (500 mg, 1.41 mmol) and 4-fluorophenol (460 mg, 5.21 mmol) in DMF/THF (1 mL/7 mL) was added K2CO3 (260 mg, 5.62 mmol) under N2. The mixture was heated at 90° C. for 8 h. The reaction mixture was concentrated in vacuo and it was extracted with EtOAc. It was washed with H2O, brine and dried over Na2SO4. After being concentrated, the residue was purified by column chromatography (PE:EA=4:1) to give the product of 6-amino-5-bromo-2-(6-(4-fluorophenoxy)pyridin-3-yl)-N-methylbenzofuran-3-carboxamide (380 mg, yield: 61%). 1H-NMR (CDCl3, 400 MHz) δ 8.61 (d, J=2.4 Hz, 1H), 8.23˜8.25 (m, 1H), 7.74 (s, 1H), 7.02˜7.09 (m, 4H), 6.91 (d, J=8.8 Hz, 1H), 8.85 (d, J=4.8 Hz, 1H), 5.76 (s, 1H), 4.20 (s, 2H), 2.95 (d, J=5.2 Hz, 3H). (M+H)+: 456/458.

Workup

concentrationThe reaction mixture was concentrated in vacuo and it
extractionwas extracted with EtOAc
washIt was washed with H2O, brine
dry with materialdried over Na2SO4
concentrationAfter being concentrated
customthe residue was purified by column chromatography (PE:EA=4:1)

Sources & evidence

ORD record: ord-b599e3f2eee1463396baefcb91473981
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242998B2

Reaction notes

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