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 595731ノート

反応式

HRID 595731 の反応式
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

参加物

7

反応物 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

生成物 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-carboxamide収率 54.9%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl触媒HCID 86622776DMF dioxane water溶媒

実験手順

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%).

後処理

  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)

出典と根拠

ORDレコード
ord-a2046e7e6722445dab14ee34a591066e
出典データセット
uspto-grants-2016_01
特許番号
US09243002B2

反応ノート

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