Potassium Phosphate, Tribasic → 5-(4-(4-fluoro-1H-indol-2-yl)-5-vinylpyrimidin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595723ノート

反応式

HRID 595723 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]=[CH2:19])=[CH:4][N:3]=1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[O:28][C:29]3[CH:39]=[C:38]([N:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])[C:37](B(O)O)=[CH:36][C:30]=3[C:31]=2[C:32](=[O:35])[NH:33][CH3:34])=[CH:23][CH:22]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.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]>[F:17][C:14]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:15]=1[CH:16]=[C:8]([C:6]1[C:5]([CH:18]=[CH2:19])=[CH:4][N:3]=[C:2]([C:37]3[C:38]([N:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])=[CH:39][C:29]4[O:28][C:27]([C:24]5[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=5)=[C:31]([C:32]([NH:33][CH3:34])=[O:35])[C:30]=4[CH:36]=3)[N:7]=1)[NH:9]2

参加物

7

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 90332474(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)boronic acidHCID 903334972-(2-chloro-5-vinylpyrimidin-4-yl)-4-fluoro-1H-indole

生成物 1

HCID 903334665-(4-(4-fluoro-1H-indol-2-yl)-5-vinylpyrimidin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide収率 68.4%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

To a degassed solution of 2-(2-chloro-5-vinylpyrimidin-4-yl)-4-fluoro-1H-indole (100 mg, 0.36 mmol) and (2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethyl sulfonamido)benzofuran-5-yl)boronic acid (150 mg, 0.36 mmol) in 1,4-dioxane (5 mL), Pd2(dba)3 (20 mg), X-Phos (20 mg) and K3PO4 (200 mg, 0.56 mmol) were added under N2. The mixture was heated to 80° C. for 2 hours. The reaction mixture was cooled to RT, filtered and washed with EtOAc. The filtrate was washed with H2O, brine, and dried over Na2SO4. After concentration, the residue was purified by column chromatography (DCM:MeOH 40:1) to give the product of 5-(4-(4-fluoro-1H-indol-2-yl)-5-vinylpyrimidin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (150 mg, yield: 68.4%). 1H-NMR (CDCl3, 400 MHz) δ 10.76 (br s, 1H), 8.88 (s, 1H), 8.63 (s, 1H), 7.98˜8.05 (m, 2H), 7.64 (s, 1H), 7.59 (s, 1H), 7.15˜7.25 (m, 6H), 6.74˜6.84 (m, 1H), 5.91 (d, J=18.0 Hz, 1H), 5.69 (d, J=11.2 Hz, 1H), 3.39 (s, 3H), 3.03 (d, J=4.8 Hz, 3H), 2.87 (s, 3H). MS (M+H)+: 614

後処理

  1. temperatureThe reaction mixture was cooled to RT
  2. filtrationfiltered
  3. washwashed with EtOAc
  4. washThe filtrate was washed with H2O, brine
  5. dry with materialdried over Na2SO4
  6. concentrationAfter concentration
  7. customthe residue was purified by column chromatography (DCM:MeOH 40:1)

出典と根拠

ORDレコード
ord-d288737bd19d40a0b8e986284701f0bb
出典データセット
uspto-grants-2016_01
特許番号
US09243002B2

反応ノート

読み込み中…