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

HRID 595728Notes

Reaction equation

HRID 595728 reaction equation
Cl[C:2]1[CH: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]=[C:19]([CH3:21])[CH3:20])=[CH:4][N:3]=1.[F:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[O:30][C:31]3[CH:41]=[C:40]([N:42]([CH3:47])[S:43]([CH3:46])(=[O:45])=[O:44])[C:39](B4OC(C)(C)C(C)(C)O4)=[CH:38][C:32]=3[C:33]=2[C:34]([NH:36][CH3:37])=[O:35])=[CH:25][CH:24]=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.O.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]>[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]=[C:19]([CH3:21])[CH3:20])=[CH:4][N:3]=[C:2]([C:39]3[C:40]([N:42]([CH3:47])[S:43]([CH3:46])(=[O:45])=[O:44])=[CH:41][C:31]4[O:30][C:29]([C:26]5[CH:27]=[CH:28][C:23]([F:22])=[CH:24][CH:25]=5)=[C:33]([C:34]([NH:36][CH3:37])=[O:35])[C:32]=4[CH:38]=3)[CH:7]=1)[NH:9]2

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 682394022-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 903339442-(2-chloro-5-(2-methylprop-1-en-1-yl)pyridin-4-yl)-4-fluoro-1H-indole

Product 1

HCID 903336115-(4-(4-fluoro-1H-indol-2-yl)-5-(2-methylprop-1-en-1-yl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideYield 81.5%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

To a degassed solution of 2-(2-chloro-5-(2-methylprop-1-en-1-yl)pyridin-4-yl)-4-fluoro-1H-indole (230 mg, 0.767 mmol) and 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (322 mg, 0.767 mmol) in 1,4-dioxane/H2O (4 mL/1 mL), Pd2(dba)3 (30 mg, 0.038 mmol), X-Phos (36 mg, 0.076 mmol) and K3PO4 (612 mg, 2.301 mmol) were added under N2 atmosphere. The mixture was stirred at 90° C. for 3 hours under N2 atmosphere. The reaction mixture was then diluted with water (100 mL) and extracted with EA (50 mL×3). The organic layer was washed with brine (10 mL), dried over Na2SO4. After concentrated, the residue was purified by column chromatography (PE:EA=2:1) to give the product of 5-(4-(4-fluoro-1H-indol-2-yl)-5-(2-methylprop-1-en-1-yl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (400 mg, yield: 81.5%). 1H-NMR (CDCl3, 400 MHz) δ 9.67 (br s, 1H), 8.61 (s, 1H), 8.20 (s, 1H), 8.09 (s, 1H), 8.00˜8.06 (m, 2H), 7.54 (s, 1H), 7.11˜7.24 (m, 4H), 6.99 (s, 1H), 6.75˜6.83 (m, 1H), 6.39 (br s, 1H), 6.01 (br s, 1H), 3.22 (s, 3H), 2.99˜3.06 (m, 6H), 2.07 (s, 3H), 1.93 (s, 3H). MS (M+H)+: 641.

Workup

  1. extractionextracted with EA (50 mL×3)
  2. washThe organic layer was washed with brine (10 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationAfter concentrated
  5. customthe residue was purified by column chromatography (PE:EA=2:1)

Sources & evidence

ORD record
ord-7eecc01382df4ac4888cac3cf2153e83
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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