Potassium Carbonate → 2-(2,4-difluorophenyl)-5-(11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595655노트

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HRID 595655 반응식
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[O:10][C:11]2[CH:21]=[C:20]([N:22]([CH3:27])[S:23]([CH3:26])(=[O:25])=[O:24])[C:19](B3OC(C)(C)C(C)(C)O3)=[CH:18][C:12]=2[C:13]=1[C:14]([NH:16][CH3:17])=[O:15].Cl[C:38]1[CH:47]=[CH:46][C:45]2[CH2:44][CH2:43][N:42]3[C:48]4[CH:49]=[CH:50][CH:51]=[C:52]([F:55])[C:53]=4[CH:54]=[C:41]3[C:40]=2[N:39]=1.C([O-])([O-])=O.[K+].[K+]>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].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[O:10][C:11]2[CH:21]=[C:20]([N:22]([CH3:27])[S:23]([CH3:26])(=[O:25])=[O:24])[C:19]([C:38]3[CH:47]=[CH:46][C:45]4[CH2:44][CH2:43][N:42]5[C:48]6[CH:49]=[CH:50][CH:51]=[C:52]([F:55])[C:53]=6[CH:54]=[C:41]5[C:40]=4[N:39]=3)=[CH:18][C:12]=2[C:13]=1[C:14]([NH:16][CH3:17])=[O:15]

참가 물질

8

반응물 3

HCID 11430Potassium CarbonateHCID 712956182-(2,4-difluorophenyl)-N-methyl-6-(N-methylmethyl sulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 903336312-Chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine

생성물 1

HCID 778455712-(2,4-difluorophenyl)-5-(11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide수율 42%

시약·촉매·용매 4

HCID 962Water촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl촉매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

To a solution of 2-(2,4-difluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (500 mg, 0.96 mmol), 2-chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine (240 mg, 0.87 mmol) and K2CO3. (241 mg, 1.75 mmol) in 1,4-dioxane (5 mL) and H2O (5 drop) were added X-Phos (10 mg) and Pd2(dba)3 (10 mg) under N2. The reaction mixture was stirred at 100° C. for 10 hours and concentrated in vacuo to remove 1,4-dioxane. The reaction mixture was extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by prep-HPLC to give the product (230 mg, yield: 42%). 1H-NMR (CDCl3, 400 MHz) δ 8.08 (s, 1H), 7.7˜57.81 (m, 1H), 7.66˜7.69 (m, 2H), 7.46 (d, J=8.0 Hz, 1H), 7.28 (s, 1H), 7.15˜7.18 (m, 2H), 6.98˜7.09 (m, 2H), 6.79 (t, J=8.4 Hz, 1H), 5.81 (br s, 1H), 4.35 (t, J=6.4 Hz, 2H), 3.39 (s, 3H), 3.32 (t, J=6.4 Hz, 2H), 2.96 (d, J=4.8 Hz, 3H), 2.68 (s, 3H). MS (M+H)+: 631.

후처리

  1. concentrationconcentrated in vacuo
  2. customto remove 1,4-dioxane
  3. extractionThe reaction mixture was extracted with EtOAc
  4. washThe organic phase was washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by prep-HPLC

출처 및 근거

ORD 기록
ord-90efcfbd4ac643e0b66c4957b0bea45d
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09243002B2

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