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Water → 5-bromo-N-methyl-6-(N-methylmethylsulfonamido)-2-(6-(trifluoromethyl)pyridin-3-yl)benzofuran-3-carboxamide

HRID 595642
Notes
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Reaction equation

HRID 595642 reaction equation
[Br:1][C:2]1[C:3]([N:16]([CH3:21])[S:17]([CH3:20])(=[O:19])=[O:18])=[CH:4][C:5]2[O:9][C:8](I)=[C:7]([C:11]([NH:13][CH3:14])=[O:12])[C:6]=2[CH:15]=1.[F:22][C:23]([F:34])([F:33])[C:24]1[N:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.C([O-])([O-])=O.[Na+].[Na+].O>O1CCOCC1.O.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]>[Br:1][C:2]1[C:3]([N:16]([CH3:21])[S:17]([CH3:20])(=[O:19])=[O:18])=[CH:4][C:5]2[O:9][C:8]([C:27]3[CH:28]=[N:29][C:24]([C:23]([F:34])([F:33])[F:22])=[CH:25][CH:26]=3)=[C:7]([C:11]([NH:13][CH3:14])=[O:12])[C:6]=2[CH:15]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 251342782-(Trifluoromethyl)pyridine-5-boronic AcidHCID 903324695-bromo-2-iodo-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

Product 1

HCID 903324615-bromo-N-methyl-6-(N-methylmethylsulfonamido)-2-(6-(trifluoromethyl)pyridin-3-yl)benzofuran-3-carboxamideYield 90%

Reagents, catalysts & solvents 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

A mixture of 5-bromo-2-iodo-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (1.5 g, 3.1 mmol), (6-(trifluoromethyl)pyridin-3-yl)boronic acid (705 mg, 3.7 mmol), Pd(dppf)Cl2 (245 mg, 0.3 mmol) and Na2CO3 (985 mg, 9.3 mmol) in dioxane/H2O (20 mL/4 mL) was stirred at 80° C. for 6 h. Water was added and the mixture was extracted with EtOAc. The organic phase was dried over Na2SO4 and concentrated in vacuum. The residue was purified by column chromatography (PE:EA=1:1) to give the product of 5-bromo-N-methyl-6-(N-methylmethylsulfonamido)-2-(6-(trifluoromethyl)pyridin-3-yl)benzofuran-3-carboxamide (1.4 g, yield: 90%). 1H-NMR (DMSO-d6, 400 MHz) δ 9.24 (s, 1H), 8.65 (d, J=4.4 Hz, 1H), 8.56 (d, J=8.0 Hz, 1H), 8.17 (s, 1H), 8.12 (d, J=8.0 Hz, 1H), 8.08 (s, 1H), 3.23 (s, 3H), 3.22 (s, 3H), 2.85 (d, J=4.4 Hz, 3H). MS (M+H)+: 506/508.

Workup

  1. extractionthe mixture was extracted with EtOAc
  2. dry with materialThe organic phase was dried over Na2SO4
  3. concentrationconcentrated in vacuum
  4. customThe residue was purified by column chromatography (PE:EA=1:1)

Sources & evidence

ORD record
ord-84623478031c4bfb9f4f6bc255473170
Source dataset
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09243002B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes