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

HRID 595683Notes

Reaction equation

HRID 595683 reaction equation
Br[C:2]1[CH:3]=[N: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+]>O1CCOCC1.O>[F:19][C:14]1[C:13]2[CH:12]=[C:9]3[N:8]([C:18]=2[CH:17]=[CH:16][CH:15]=1)[CH2:7][CH2:6][C:5]1[N:4]=[CH:3][C:2]([C:37]2[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:34][CH3:35])=[O:33])[C:30]=4[CH:36]=2)=[CH:11][C:10]3=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 682394022-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 903336942-Bromo-11-fluoro-5,6-dihydroindolo[2,1-f][1,6]naphthyridine

Product 1

HCID 778458465-(11-fluoro-5,6-dihydroindolo[2,1-f][1,6]naphthyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideYield 41.7%

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-bromo-11-fluoro-5,6-dihydroindolo[2,1-f][1,6]naphthyridine (50 mg, 0.16 mmol), 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (87 mg, 0.17 mmol), potassium carbonate (43 mg, 0.32 mmol) and Pd(dtbpf)Cl2 (10 mg) in 1,4-dioxane/water (1/0.1 mL) was stirred at 100° C. for 6 hours under nitrogen atmosphere. The mixture was filtered through Celite pad and concentrated, and then the residue was diluted with water and EA. After extraction with EA, the combined organic phase was washed with brine, dried over sodium sulfate and concentrated to afford the desired product (40 mg, yield: 41.7%) through the prep-HPLC. 1H-NMR (CDCl3, 400 MHz) δ 8.50 (s, 1H), 8.19 (s, 1H), 7.93˜7.96 (m, 2H), 7.90 (s, 1H), 7.65 (s, 1H), 7.19˜7.24 (m, 2H), 7.15˜7.17 (m, 2H), 7.02 (s, 1H), 6.77˜6.82 (m, 1H), 5.88 (br s, 1H), 4.41˜4.44 (m, 2H), 3.45˜3.49 (m, 2H), 3.18 (s, 3H), 2.99 (d, J=4.80 Hz, 3H), 2.84 (s, 3H). MS (M+H)+: 613.

Workup

  1. filtrationThe mixture was filtered through Celite pad
  2. concentrationconcentrated
  3. additionthe residue was diluted with water and EA
  4. extractionAfter extraction with EA
  5. washthe combined organic phase was washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-4cdb1e1dba5649efb086e8417485f20a
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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