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

HRID 595650노트

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HRID 595650 반응식
[CH:1]([N:4]1[C:8]([C:9]2[O:10][C:11]3[CH:21]=[C:20]([N:22]([CH3:27])[S:23]([CH3:26])(=[O:25])=[O:24])[C:19](B4OC(C)(C)C(C)(C)O4)=[CH:18][C:12]=3[C:13]=2[C:14]([NH:16][CH3:17])=[O:15])=[CH:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].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+].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:55][C:52]1[C:53]2[CH:54]=[C:41]3[C:40]4[N:39]=[C:38]([C:19]5[C:20]([N:22]([CH3:27])[S:23]([CH3:26])(=[O:25])=[O:24])=[CH:21][C:11]6[O:10][C:9]([C:8]7[N:4]([CH:1]([CH3:3])[CH3:2])[N:5]=[CH:6][CH:7]=7)=[C:13]([C:14]([NH:16][CH3:17])=[O:15])[C:12]=6[CH:18]=5)[CH:47]=[CH:46][C:45]=4[CH2:44][CH2:43][N:42]3[C:48]=2[CH:49]=[CH:50][CH:51]=1

참가 물질

8

반응물 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 903336312-Chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridineHCID 903339132-(1-isopropyl-1H-pyrazol-5-yl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide

생성물 1

HCID 778453395-(11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-2-yl)-2-(1-isopropyl-1H-pyrazol-5-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide수율 42%

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 2-(1-isopropyl-1H-pyrazol-5-yl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (78 mg, 0.14 mmol), 2-chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine (35 mg, 0.13 mmol) and K2CO3 (27 mg, 0.19 mmol) in 1,4-dioxane (0.8 mL) and water (0.05 mL) were added X-Phos (10 mg) and Pd2(dba)3 (20 mg) under nitrogen. The mixture was heated at 120° C. for 2 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 in vacuo. The crude product was purified by the prep-HPLC to give the desired compound (30 mg, yield: 42%). 1H-NMR (CDCl3, 400 MHz) δ 8.41 (s, 1H), 7.72 (s, 1H), 7.69 (d, J=7.6 Hz, 1H), 7.47 (d, J=7.6 Hz, 1H), 7.28 (s, 1H), 7.17˜7.19 (m, 2H), 6.79˜6.83 (m, 1H), 6.69 (s, 1H), 5.85 (s, 1H), 4.61˜4.64 (m, 1H), 4.35˜4.38 (m, 2H), 3.44 (s, 3H), 3.32˜3.56 (m, 2H), 2.90 (d, J=5.2 Hz, 3H), 2.64 (s, 3H). MS (M+H)+: 627.

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 in vacuo
  6. customThe crude product was purified by the prep-HPLC

출처 및 근거

ORD 기록
ord-553149cbcfb143b6995aba94fc6ef9e7
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09243002B2

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