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

HRID 595662ノート

反応式

HRID 595662 の反応式
[CH3:1][NH:2][C:3]([C:5]1[C:9]2[CH:10]=[C:11](B3OC(C)(C)C(C)(C)O3)[C:12]([N:14]([CH3:19])[S:15]([CH3:18])(=[O:17])=[O:16])=[CH:13][C:8]=2[O:7][C:6]=1[N:29]1[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][C:30]1=[O:36])=[O:4].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:11]5[C:12]([N:14]([CH3:19])[S:15]([CH3:18])(=[O:16])=[O:17])=[CH:13][C:8]6[O:7][C:6]([N:29]7[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][C:30]7=[O:36])=[C:5]([C:3]([NH:2][CH3:1])=[O:4])[C:9]=6[CH:10]=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

7

反応物 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 90333625N-methyl-2-(4-methyl-2-oxopyridin-1 (2H)-yl)-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 778451105-(11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-2-yl)-N-methyl-2-(4-methyl-2-oxopyridin-1 (2H)-yl)-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide収率 25.2%

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
80 °C

実験手順

To a mixture of N-methyl-2-(4-methyl-2-oxopyridin-1 (2H)-yl)-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (100 mg, 0.19 mmol), 2-chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine (63 mg, 0.23 mmol) and K2CO3 (54 mg, 0.39 mmol) in 1,4-dioxane/H2O (3 mL/0.1 mL) were added X-Phos (10 mg) and Pd2(dba)3 (10 mg) under N2. The reaction mixture was stirred at 80° C. for 5 hours and concentrated in vacuo to remove 1,4-dioxane. The reaction mixture was extracted with EtOAc, washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by prep-HPLC to give the product (30 mg, yield: 24%). 1H-NMR (CDCl3, 400 MHz) δ 8.17 (s, 1H), 7.83˜7.85 (m, 1H), 7.66˜7.68 (m, 2H), 7.44 (d, J=8.0 Hz, 1H), 7.26˜7.18 (m, 2H), 7.14˜7.18 (m, 2H), 6.77˜6.81 (m, 1H), 6.53 (s, 1H), 6.29 (d, J=8.0 Hz, 1H), 4.34 (t, J=6.4 Hz, 2H), 3.40 (s, 3H), 3.31 (t, J=6.4 Hz, 2H), 2.90 (d, J=4.8 Hz, 3H), 2.61 (s, 3H), 2.32 (s, 3H). MS (M+H)+: 626.

後処理

  1. concentrationconcentrated in vacuo
  2. customto remove 1,4-dioxane
  3. extractionThe reaction mixture was extracted with EtOAc
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by prep-HPLC

出典と根拠

ORDレコード
ord-520e1d8559d34964bfa4b0d0d5b4c4e5
出典データセット
uspto-grants-2016_01
特許番号
US09243002B2

反応ノート

読み込み中…