Potassium Carbonate → 5-(11-fluoro-5,6-dihydroindolo[2,1-a][2,6]naphthyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595676Notes

Reaction equation

HRID 595676 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[CH2:6][CH2:7][N:8]3[C:18]4[CH:17]=[CH:16][CH:15]=[C:14]([F:19])[C:13]=4[CH:12]=[C:9]3[C:10]=2[CH:11]=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.C([O-])([O-])=O.[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.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:19][C:14]1[C:13]2[CH:12]=[C:9]3[C:10]4[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]=[CH:4][C:5]=4[CH2:6][CH2:7][N:8]3[C:18]=2[CH:17]=[CH:16][CH:15]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 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 903334612-Chloro-11-fluoro-5,6-dihydroindolo[2,1-a][2,6]naphthyridine

Product 1

HCID 778457635-(11-fluoro-5,6-dihydroindolo[2,1-a][2,6]naphthyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideYield 31.4%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of compound 2-chloro-11-fluoro-5,6-dihydroindolo[2,1-a][2,6]naphthyridine (70 mg, 0.26 mmol), 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (155 mg, 0.31 mmol) and K2CO3 (53 mg, 0.38 mmol) in 1,4-dioxane (2 mL) and water (0.05 mL) were added X-Phos (10 mg) and Pd2(dba)3 (10 mg) under nitrogen. The mixture was heated at 120° C. for 3 hours and filtered through the celite pad. The filtrate was extracted with EtOAc, then the combined organic phase was washed with brine, dried over Na2SO4 and concentrated. The crude product was purified by prep-HPLC to give the desired compound (50 mg, yield: 30%). 1H-NMR (CDCl3, 400 MHz) δ 8.54 (s, 1H), 7.91˜7.98 (m, 4H), 7.62 (s, 1H), 7.09˜7.16 (m, 5H), 6.74 (t, J=8.8 Hz, 1H), 5.95 (s, 1H), 4.29 (t, J=6.0 Hz, 2H), 3.23 (t, J=6.0 Hz, 2H), 3.17 (s, 3H), 2.95 (d, J=4.0 Hz, 3H), 2.83 (s, 3H). MS (M+H)+: 613.

Workup

  1. filtrationfiltered through the celite pad
  2. extractionThe filtrate was extracted with EtOAc
  3. washthe combined organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude product was purified by prep-HPLC

Sources & evidence

ORD record
ord-5067993cd8464abfa38390bbe393ef2e
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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