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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 595676
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HRID 595676 반응식
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
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참가 물질

8

반응물 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

생성물 1

HCID 77845763
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
수율 31.4%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
120 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-5067993cd8464abfa38390bbe393ef2e
출처 데이터셋
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09243002B2

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