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

HRID 595736

反応式

HRID 595736 の反応式
Cl[C:2]1[CH:11]=[CH:10][C:9]2[CH2:8][CH:7]([CH2:12][CH2:13][N:14]3[CH2:17][CH:16]([F:18])[CH2:15]3)[N:6]3[C:19]4[CH:20]=[CH:21][CH:22]=[C:23]([F:26])[C:24]=4[CH:25]=[C:5]3[C:4]=2[N:3]=1.[CH3:27][NH:28][C:29]([C:31]1[C:35]2[CH:36]=[C:37](B3OC(C)(C)C(C)(C)O3)[C:38]([N:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])=[CH:39][C:34]=2[O:33][C:32]=1[C:55]1[CH:56]=[N:57][C:58]([CH3:61])=[CH:59][CH:60]=1)=[O:30].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:26][C:23]1[C:24]2[CH:25]=[C:5]3[C:4]4[N:3]=[C:2]([C:37]5[C:38]([N:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])=[CH:39][C:34]6[O:33][C:32]([C:55]7[CH:56]=[N:57][C:58]([CH3:61])=[CH:59][CH:60]=7)=[C:31]([C:29]([NH:28][CH3:27])=[O:30])[C:35]=6[CH:36]=5)[CH:11]=[CH:10][C:9]=4[CH2:8][CH:7]([CH2:12][CH2:13][N:14]4[CH2:17][CH:16]([F:18])[CH2:15]4)[N:6]3[C:19]=2[CH:20]=[CH:21][CH:22]=1

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 903336042-Chloro-11-fluoro-6-(2-(3-fluoroazetidin-1-yl)ethyl)-5,6-dihydroindolo[1,2-h][1,7]naphthyridineHCID 90333863N-methyl-6-(N-methylmethylsulfonamido)-2-(6-methylpyridin-3-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide

生成物 1

HCID 903410475-(11-fluoro-6-(2-(3-fluoroazetidin-1-yl)ethyl)-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)-2-(6-methylpyridin-3-yl)benzofuran-3-carboxamide収率 44.9%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 218864351,4-Dioxane--water (1/1)溶媒

反応条件

温度
110 °C

実験手順

A mixture of 2-chloro-11-fluoro-6-(2-(3-fluoroazetidin-1-yl)ethyl)-5,6-dihydroindolo[1,2-h][1,7]naphthyridine (100 mg, 0.269 mmol), N-methyl-6-(N-methylmethylsulfonamido)-2-(6-methylpyridin-3-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (150 mg, 0.295 mmol), K2CO3 (75 mg, 0.537 mmol), Pd2(dba)3 (15 mg, 0.027 mmol) and X-Phos (10 mg, 0.054 mmol) in dioxane/H2O (4 mL/10 d) was stirred at 110° C. for 4 hours under N2 atmosphere. The mixture was then filtered through Celite and concentrated. The residue was purified by column chromatography (PE:EA=2:1) to afford the desired product of 5-(11-fluoro-6-(2-(3-fluoroazetidin-1-yl)ethyl)-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)-2-(6-methylpyridin-3-yl)benzofuran-3-carboxamide (85 mg, yield: 44.9%). 1H-NMR (CDCl3, 400 MHz) δ 8.97 (s, 1H), 8.17 (t, J=6.0, 2.0 Hz, 1H), 8.00 (s, 1H), 7.61 (t, J=8.0 Hz, 2H), 7.39 (d, J=8.0 Hz, 1H), 7.24 (d, J=6.8 Hz, 2H), 7.12 (s, 2H), 6.73˜6.77 (m, 1H), 5.97 (d, J=4.8 Hz, 1H), 4.97˜5.14 (m, 1H), 4.95 (d, J=6.0 Hz, 1H), 3.49˜3.56 (m, 4H), 3.33 (s, 3H), 3.00˜3.06 (m, 3H), 2.95 (d, J=4.8 Hz, 3H), 2.62 (s, 3H), 2.58 (s, 3H), 2.33˜2.36 (m, 1H), 1.59˜1.56 (m, 2H). MS (M+H)+: 711.

後処理

  1. filtrationThe mixture was then filtered through Celite
  2. concentrationconcentrated
  3. customThe residue was purified by column chromatography (PE:EA=2:1)

出典と根拠

ORDレコード
ord-9de3fa9a624c4bc6947f6440bddb21a1
出典データセット
uspto-grants-2016_01
特許番号
US09243002B2

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