Potassium Phosphate, Tribasic → 5-(10-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595660Notes

Reaction equation

HRID 595660 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:9]2[CH2:8][CH2:7][N:6]3[C:12]4[CH:13]=[CH:14][C:15]([F:19])=[CH:16][C:17]=4[CH:18]=[C:5]3[C:4]=2[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](B4OC(C)(C)C(C)(C)O4)=[CH:36][C:30]=3[C:31]=2[C:32]([NH:34][CH3:35])=[O:33])=[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:19][C:15]1[CH:14]=[CH:13][C:12]2[N:6]3[CH2:7][CH2:8][C:9]4[CH:10]=[CH:11][C:2]([C:37]5[C:38]([N:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])=[CH:39][C:29]6[O:28][C:27]([C:24]7[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=7)=[C:31]([C:32]([NH:34][CH3:35])=[O:33])[C:30]=6[CH:36]=5)=[N:3][C:4]=4[C:5]3=[CH:18][C:17]=2[CH:16]=1

Participants

7

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 903334282-Chloro-10-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine

Product 1

HCID 778456665-(10-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideYield 61.5%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

To a degassed solution of 2-chloro-10-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine (50 mg, 0.18 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 (80 mg, 0.16 mmol) in 1,4-dioxane (5 mL), Pd2(dba)3 (10 mg), X-Phos (10 mg) and K3PO4 (100 mg, 0.38 mmol) were added under N2. After heated to 100° C. for 1 hour, the reaction mixture was cooled to RT, filtered and washed with EtOAc. The filtrate was washed with H2O, brine, dried over Na2SO4. After concentrated, the residue was purified by prep-HPLC to give the product (60 mg, yield: 61.5%). 1H-NMR (CDCl3, 400 MHz) δ 7.99 (s, 1H), 7.92˜7.98 (m, 2H), 7.65˜7.67 (m, 2H), 7.43 (d, J=7.6 Hz, 1H), 7.28˜7.32 (m, 2H), 7.15˜7.24 (m, 3H), 6.98˜7.03 (m, 1H), 6.05 (br s, 1H), 4.31 (t, J=6.4 Hz, 2H), 3.36 (s, 3H), 3.30 (t, J=6.4 Hz, 2H), 2.97 (d, J=4.8 Hz, 3H), 2.68 (s, 3H). MS (M+H)+: 613.

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 concentrated
  7. customthe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-88338c357b75435b93df5d67baca4d9f
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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