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

HRID 595683ノート

反応式

HRID 595683 の反応式
Br[C:2]1[CH:3]=[N:4][C:5]2[CH2:6][CH2:7][N:8]3[C:18]4[CH:17]=[CH:16][CH:15]=[C:14]([F:19])[C:13]=4[CH:12]=[C:9]3[C:10]=2[CH:11]=1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[O:28][C:29]3[CH:39]=[C:38]([N:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])[C:37](B4OC(C)(C)C(C)(C)O4)=[CH:36][C:30]=3[C:31]=2[C:32]([NH:34][CH3:35])=[O:33])=[CH:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[F:19][C:14]1[C:13]2[CH:12]=[C:9]3[N:8]([C:18]=2[CH:17]=[CH:16][CH:15]=1)[CH2:7][CH2:6][C:5]1[N:4]=[CH:3][C:2]([C:37]2[C:38]([N:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])=[CH:39][C:29]4[O:28][C:27]([C:24]5[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=5)=[C:31]([C:32]([NH:34][CH3:35])=[O:33])[C:30]=4[CH:36]=2)=[CH:11][C:10]3=1

参加物

5

反応物 3

HCID 11430Potassium CarbonateHCID 682394022-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 903336942-Bromo-11-fluoro-5,6-dihydroindolo[2,1-f][1,6]naphthyridine

生成物 1

HCID 778458465-(11-fluoro-5,6-dihydroindolo[2,1-f][1,6]naphthyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide収率 41.7%

試薬・触媒・溶媒 1

HCID 218864351,4-Dioxane--water (1/1)溶媒

反応条件

温度
100 °C

実験手順

A mixture of 2-bromo-11-fluoro-5,6-dihydroindolo[2,1-f][1,6]naphthyridine (50 mg, 0.16 mmol), 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (87 mg, 0.17 mmol), potassium carbonate (43 mg, 0.32 mmol) and Pd(dtbpf)Cl2 (10 mg) in 1,4-dioxane/water (1/0.1 mL) was stirred at 100° C. for 6 hours under nitrogen atmosphere. The mixture was filtered through Celite pad and concentrated, and then the residue was diluted with water and EA. After extraction with EA, the combined organic phase was washed with brine, dried over sodium sulfate and concentrated to afford the desired product (40 mg, yield: 41.7%) through the prep-HPLC. 1H-NMR (CDCl3, 400 MHz) δ 8.50 (s, 1H), 8.19 (s, 1H), 7.93˜7.96 (m, 2H), 7.90 (s, 1H), 7.65 (s, 1H), 7.19˜7.24 (m, 2H), 7.15˜7.17 (m, 2H), 7.02 (s, 1H), 6.77˜6.82 (m, 1H), 5.88 (br s, 1H), 4.41˜4.44 (m, 2H), 3.45˜3.49 (m, 2H), 3.18 (s, 3H), 2.99 (d, J=4.80 Hz, 3H), 2.84 (s, 3H). MS (M+H)+: 613.

後処理

  1. filtrationThe mixture was filtered through Celite pad
  2. concentrationconcentrated
  3. additionthe residue was diluted with water and EA
  4. extractionAfter extraction with EA
  5. washthe combined organic phase was washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated

出典と根拠

ORDレコード
ord-4cdb1e1dba5649efb086e8417485f20a
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…