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

HRID 595652ノート

反応式

HRID 595652 の反応式
[F:1][CH:2]([F:37])[C:3]1[CH:8]=[CH:7][C:6]([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:5][CH:4]=1.Cl[C:39]1[CH:48]=[CH:47][C:46]2[CH2:45][CH2:44][N:43]3[C:49]4[CH:50]=[CH:51][CH:52]=[C:53]([F:56])[C:54]=4[CH:55]=[C:42]3[C:41]=2[N:40]=1.C([O-])([O-])=O.[Na+].[Na+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.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].O>[F:1][CH:2]([F:37])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:10][C:11]3[CH:21]=[C:20]([N:22]([CH3:27])[S:23]([CH3:26])(=[O:24])=[O:25])[C:19]([C:39]4[CH:48]=[CH:47][C:46]5[CH2:45][CH2:44][N:43]6[C:49]7[CH:50]=[CH:51][CH:52]=[C:53]([F:56])[C:54]=7[CH:55]=[C:42]6[C:41]=5[N:40]=4)=[CH:18][C:12]=3[C:13]=2[C:14]([NH:16][CH3:17])=[O:15])=[CH:5][CH:4]=1

参加物

8

反応物 4

HCID 10340Sodium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 903335872-(4-(difluoromethyl)phenyl)-N-methyl-6-(N-methylmethylsulfonamido)-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

生成物 1

HCID 778455702-(4-(difluoromethyl)phenyl)-5-(11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide収率 21.2%

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
100 °C

実験手順

To a degassed solution of 2-(4-(difluoromethyl)phenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (120 mg, 0.22 mmol), 2-chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine (64 mg, 0.22 mmol), Na2CO3 (62 mg, 0.45 mmol), in 1,4-dioxane (3 mL) and H2O (0.1 mL) was added Pd2(dba)3 (5 mg) and X-Phos (5 mg) under N2. Then the mixture was stirred at 100° C. for 2 hours. The reaction mixture was cooled to RT and filtered. The filtrate was washed with H2O and dried over Na2SO4. After concentrated, the residue was purified by prep-HPLC to give the product (30 mg, yield: 21%). 1H-NMR (CDCl3, 400 MHz) δ 8.08 (d, J=8.0 Hz, 2H), 8.03 (s, 1H), 7.74˜7.64 (m, 4H), 7.47 (d, J=7.6 Hz, 1H), 7.30 (s, 1H), 7.22˜7.14 (m, 2H), 6.89˜6.81 (m, 1H), 6.81˜6.73 (m, 1H), 6.00 (d, J=4.4 Hz, 1H), 4.37 (t, J=6.4 Hz, 2H), 3.40 (s, 3H), 3.34 (t, J=6.4 Hz, 2H), 3.02 (d, J=4.8 Hz, 3H), 2.72 (s, 3H). MS (M+H)+: 645.

後処理

  1. temperatureThe reaction mixture was cooled to RT
  2. filtrationfiltered
  3. washThe filtrate was washed with H2O
  4. dry with materialdried over Na2SO4
  5. concentrationAfter concentrated
  6. customthe residue was purified by prep-HPLC

出典と根拠

ORDレコード
ord-a73c50e9d7ee44ba99d0268b7c0c148d
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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