Sodium Carbonate → 5-(6-(4-fluoro-1H-indol-2-yl)-5-(4-hydroxybut-1-en-1-yl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595731Notes

Reaction equation

HRID 595731 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[NH:9][C:10]3[C:15]([CH:16]=2)=[C:14]([F:17])[CH:13]=[CH:12][CH:11]=3)[C:5]([CH:18]=[CH:19][CH2:20][CH2:21][OH:22])=[CH:4][CH:3]=1.[F:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[O:31][C:32]3[CH:42]=[C:41]([N:43]([CH3:48])[S:44]([CH3:47])(=[O:46])=[O:45])[C:40](B(O)O)=[CH:39][C:33]=3[C:34]=2[C:35](=[O:38])[NH:36][CH3:37])=[CH:26][CH:25]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.CN(C=O)C.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>[F:17][C:14]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:15]=1[CH:16]=[C:8]([C:6]1[N:7]=[C:2]([C:40]3[C:41]([N:43]([CH3:48])[S:44]([CH3:47])(=[O:46])=[O:45])=[CH:42][C:32]4[O:31][C:30]([C:27]5[CH:28]=[CH:29][C:24]([F:23])=[CH:25][CH:26]=5)=[C:34]([C:35]([NH:36][CH3:37])=[O:38])[C:33]=4[CH:39]=3)[CH:3]=[CH:4][C:5]=1[CH:18]=[CH:19][CH2:20][CH2:21][OH:22])[NH:9]2

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 90332474(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)boronic acidHCID 1232322814-(6-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-yl)but-3-en-1-ol

Product 1

HCID 1235515905-(6-(4-fluoro-1H-indol-2-yl)-5-(4-hydroxybut-1-en-1-yl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideYield 54.9%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalystHCID 86622776DMF dioxane waterSolvent

Procedure

A solution of 4-(6-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-yl)but-3-en-1-ol (500 mg, 1.58 mmol), (2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethyl sulfonamido)benzofuran-5-yl)boronic acid (800 mg, 1.89 mmol) and Na2CO3 (340 mg, 3.15 mmol) in dioxane/DMF/H2O (5 mL/1 mL/0.2 mL) was added Pd2(dba)3 (10 mg) and X-Phos (10 mg) under N2. It was put into a pre-heated oil-bath at 110° C. for 8 hours. The mixture was concentrated and it was extracted with EtOAc. The combined organic phase was washed with brine, and dried over Na2SO4. The crude product was purified by column (PE:EA=1:1) to give the pure product of (Z and E)-5-(6-(4-fluoro-1H-indol-2-yl)-5-(4-hydroxybut-1-en-1-yl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (570 mg, yield: 52%).

Workup

  1. concentrationThe mixture was concentrated
  2. extractionit was extracted with EtOAc
  3. washThe combined organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. customThe crude product was purified by column (PE:EA=1:1)

Sources & evidence

ORD record
ord-a2046e7e6722445dab14ee34a591066e
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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