Potassium Phosphate, Tribasic → 5-(10-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595660ノート

反応式

HRID 595660 の反応式
Cl[C:2]1[CH:11]=[CH:10][C:9]2[CH2:8][CH2:7][N:6]3[C:12]4[CH:13]=[CH:14][C:15]([F:19])=[CH:16][C:17]=4[CH:18]=[C:5]3[C:4]=2[N:3]=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.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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]>[F:19][C:15]1[CH:14]=[CH:13][C:12]2[N:6]3[CH2:7][CH2:8][C:9]4[CH:10]=[CH:11][C:2]([C:37]5[C:38]([N:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])=[CH:39][C:29]6[O:28][C:27]([C:24]7[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=7)=[C:31]([C:32]([NH:34][CH3:35])=[O:33])[C:30]=6[CH:36]=5)=[N:3][C:4]=4[C:5]3=[CH:18][C:17]=2[CH:16]=1

参加物

7

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 682394022-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 903334282-Chloro-10-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine

生成物 1

HCID 778456665-(10-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide収率 61.5%

試薬・触媒・溶媒 2

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

反応条件

温度
100 °C

実験手順

To a degassed solution of 2-chloro-10-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine (50 mg, 0.18 mmol) and 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (80 mg, 0.16 mmol) in 1,4-dioxane (5 mL), Pd2(dba)3 (10 mg), X-Phos (10 mg) and K3PO4 (100 mg, 0.38 mmol) were added under N2. After heated to 100° C. for 1 hour, the reaction mixture was cooled to RT, filtered and washed with EtOAc. The filtrate was washed with H2O, brine, dried over Na2SO4. After concentrated, the residue was purified by prep-HPLC to give the product (60 mg, yield: 61.5%). 1H-NMR (CDCl3, 400 MHz) δ 7.99 (s, 1H), 7.92˜7.98 (m, 2H), 7.65˜7.67 (m, 2H), 7.43 (d, J=7.6 Hz, 1H), 7.28˜7.32 (m, 2H), 7.15˜7.24 (m, 3H), 6.98˜7.03 (m, 1H), 6.05 (br s, 1H), 4.31 (t, J=6.4 Hz, 2H), 3.36 (s, 3H), 3.30 (t, J=6.4 Hz, 2H), 2.97 (d, J=4.8 Hz, 3H), 2.68 (s, 3H). MS (M+H)+: 613.

後処理

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

出典と根拠

ORDレコード
ord-88338c357b75435b93df5d67baca4d9f
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…