5-(6-(4-fluoro-1H-indol-2-yl)-5-(4-hydroxybut-1-en-1-yl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide → 5-(11-fluoro-6-(2-hydroxyethyl)-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595732Notes

Reaction equation

HRID 595732 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[N:16]=[C:15]([C:17]3[C:18]([N:37]([CH3:42])[S:38]([CH3:41])(=[O:40])=[O:39])=[CH:19][C:20]4[O:24][C:23]([C:25]5[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=5)=[C:22]([C:32]([NH:34][CH3:35])=[O:33])[C:21]=4[CH:36]=3)[CH:14]=[CH:13][C:12]=1[CH:43]=[CH:44][CH2:45][CH2:46][OH:47])[NH:6]2>CC(N(C)C)=O.O>[F:1][C:2]1[C:3]2[CH:4]=[C:5]3[C:11]4[N:16]=[C:15]([C:17]5[C:18]([N:37]([CH3:42])[S:38]([CH3:41])(=[O:40])=[O:39])=[CH:19][C:20]6[O:24][C:23]([C:25]7[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=7)=[C:22]([C:32]([NH:34][CH3:35])=[O:33])[C:21]=6[CH:36]=5)[CH:14]=[CH:13][C:12]=4[CH2:43][CH:44]([CH2:45][CH2:46][OH:47])[N:6]3[C:7]=2[CH:8]=[CH:9][CH:10]=1

Participants

4

Reactant 1

HCID 1235515905-(6-(4-fluoro-1H-indol-2-yl)-5-(4-hydroxybut-1-en-1-yl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

Product 1

HCID 903339405-(11-fluoro-6-(2-hydroxyethyl)-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideYield 33.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

A solution of (Z and E)-5-(6-(4-fluoro-1H-indol-2-yl)-5-(4-hydroxybut-1-en-1-yl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (300 mg, 0.457 mmol) in DMAc (9 mL) was added K3PO4.3H2O (606 mg, 2.28 mmol) under N2. It was put into a pre-heated oil-bath at 110° C. for 3 hours. The mixture was diluted with H2O and it was extracted with EtOAc (500 mL×5). The combined organic phase was washed with brine, and dried over Na2SO4. The crude product was purified with Prep-HPLC to give the pure product of 5-(11-fluoro-6-(2-hydroxyethyl)-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (100 mg, yield: 30%). 1H-NMR (CDCl3, 400 MHz) δ 7.97 (s, 1H), 7.88˜7.92 (m, 2H), 7.63 (s, 1H), 7.60 (s, 1H), 7.40 (d, J=8.0 Hz, 1H), 7.09˜7.22 (m, 5H), 6.72 (t, J=8.4 Hz, 1H), 5.83 (s, 1H), 5.02 (d, J=6.4 Hz, 1H), 3.43˜3.55 (m, 4H), 3.35 (s, 3H), 3.10 (d, J=24.0 Hz, 1H), 2.94 (d, J=4.4 Hz, 3H), 2.61 (s, 3H), 1.78 (d, J=5.2 Hz, 2H). MS (M+H)+: 657.

Workup

  1. extractionwas extracted with EtOAc (500 mL×5)
  2. washThe combined organic phase was washed with brine
  3. dry with materialdried over Na2SO4
  4. customThe crude product was purified with Prep-HPLC

Sources & evidence

ORD record
ord-ad18aed1ffba48769273ab4f72f60e87
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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