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 595723Notes

Reaction equation

HRID 595723 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]=[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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

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

Workup

  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)

Sources & evidence

ORD record
ord-d288737bd19d40a0b8e986284701f0bb
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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