2,4-Difluoro-1-iodobenzene → 6-amino-5-bromo-2-(2,4-difluorophenyl)-N-methylbenzofuran-3-carboxamide

HRID 595653Notes

Reaction equation

[NH2:1][C:2]1[C:17]([Br:18])=[CH:16][C:5]2[C:6]([C:12](=[O:15])[NH:13][CH3:14])=[C:7](B(O)O)[O:8][C:4]=2[CH:3]=1.[F:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1I>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:1][C:2]1[C:17]([Br:18])=[CH:16][C:5]2[C:6]([C:12]([NH:13][CH3:14])=[O:15])=[C:7]([C:23]3[CH:22]=[CH:21][C:20]([F:19])=[CH:25][C:24]=3[F:26])[O:8][C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 15 °C

Procedure

To a mixture of (6-amino-5-bromo-3-(methylcarbamoyl)benzofuran-2-yl)boronic acid (4.78 g, 11.46 mmol), K3PO4.3H2O (8.32 g, 31.25 mmol) and 2,4-difluoro-1-iodobenzene (2.50 g, 10.42 mmol) in DMF (25 mL) was added Pd(dppf)Cl2 (380 mg, 0.52 mmol) under N2, and then the mixture was stirred at 15° C. for 3 hours. After the solvent was removed, EtOAc/H2O (10 mL/20 mL) was added to the mixture. After stirring 15 minutes, the resulting solid was filtered to give the product of 6-amino-5-bromo-2-(2,4-difluorophenyl)-N-methylbenzofuran-3-carboxamide (2.80 g, yield: 70%). 1H-NMR (DMSO-d6, 400 MHz) δ 8.06 (d, J=1.6 Hz, 1H), 7.74 (d, J=10.4 Hz, 1H), 7.70 (s, 1H), 7.41 (s, 1H), 7.24 (s, 1H), 7.00 (s, 1H), 5.58 (br s, 2H), 2.76 (s, 3H). MS (M+H)+: 281/283

Workup

customAfter the solvent was removed
additionEtOAc/H2O (10 mL/20 mL) was added to the mixture
stirringAfter stirring 15 minutes
filtrationthe resulting solid was filtered

Sources & evidence

ORD record: ord-95cb501410ad4f28881291adcb92963a
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09243002B2

Reaction notes

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