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 595650ノート

反応式

HRID 595650 の反応式
[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

参加物

8

反応物 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

生成物 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-carboxamide収率 42%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-553149cbcfb143b6995aba94fc6ef9e7
出典データセット
uspto-grants-2016_01
特許番号
US09243002B2

反応ノート

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