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

HRID 595729Notes

Reaction equation

HRID 595729 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:11]1[C:16]([CH:17]=[C:18]([CH3:20])[CH3:19])=[CH:15][N:14]=[C:13]([C:21]3[C:22]([N:41]([CH3:46])[S:42]([CH3:45])(=[O:44])=[O:43])=[CH:23][C:24]4[O:28][C:27]([C:29]5[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=5)=[C:26]([C:36]([NH:38][CH3:39])=[O:37])[C:25]=4[CH:40]=3)[CH:12]=1)[NH:6]2.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC(N(C)C)=O.O>[F:1][C:2]1[C:3]2[CH:4]=[C:5]3[C:11]4[CH:12]=[C:13]([C:21]5[C:22]([N:41]([CH3:46])[S:42]([CH3:45])(=[O:43])=[O:44])=[CH:23][C:24]6[O:28][C:27]([C:29]7[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=7)=[C:26]([C:36]([NH:38][CH3:39])=[O:37])[C:25]=6[CH:40]=5)[N:14]=[CH:15][C:16]=4[CH2:17][C:18]([CH3:20])([CH3:19])[N:6]3[C:7]=2[CH:8]=[CH:9][CH:10]=1

Participants

5

Reactant 2

HCID 62657Potassium Phosphate, TribasicHCID 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-carboxamide

Product 1

HCID 903339595-(11-fluoro-6,6-dimethyl-5,6-dihydroindolo[2,1-a][2,6]naphthyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideYield 40%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture 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 (100 mg, 0.156 mmol) and K3PO4 (166 mg, 0.781 mmol) in DMAc (0.8 mL) was stirred at 100° C. overnight. The mixture was then diluted with water (40 mL) and extracted with EA (20 mL*3). The organic layer was washed with brine (30 mL*3), dried over Na2SO4 and concentrated. The residue was purified by prep-TLC (DCM:EA=1:1) to afford the product of 5-(11-fluoro-6,6-dimethyl-5,6-dihydroindolo[2,1-a][2,6]naphthyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (40 mg, yield: 40.0%). 1H-NMR (CDCl3, 400 MHz) δ 8.49 (s, 1H), 7.86˜8.00 (m, 4H), 7.61 (s, 1H), 7.45 (d, J=8.0 Hz, 1H), 7.00˜7.18 (m, 4H), 6.72 (t, J=8.4 Hz, 1H), 6.01 (br s, 1H), 3.16 (s, 3H), 3.08 (br s, 2H), 2.93 (d, J=4.4 Hz, 3H), 2.77 (s, 3H), 1.69 (br s, 6H). MS (M+H)+: 641.

Workup

  1. extractionextracted with EA (20 mL*3)
  2. washThe organic layer was washed with brine (30 mL*3)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by prep-TLC (DCM:EA=1:1)

Sources & evidence

ORD record
ord-7c51dd5ae22f41ab9c15433c2f4a58f3
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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