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

HRID 595672ノート

反応式

HRID 595672 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[C:29]1[S:33][C:32]([CH3:34])=[N:31][CH:30]=1)=[O:4].Cl[C:36]1[CH:45]=[CH:44][C:43]2[CH2:42][CH2:41][N:40]3[C:46]4[CH:47]=[CH:48][CH:49]=[C:50]([F:53])[C:51]=4[CH:52]=[C:39]3[C:38]=2[N:37]=1.C([O-])([O-])=O.[Na+].[Na+].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:53][C:50]1[C:51]2[CH:52]=[C:39]3[C:38]4[N:37]=[C:36]([C:11]5[C:12]([N:14]([CH3:19])[S:15]([CH3:18])(=[O:17])=[O:16])=[CH:13][C:8]6[O:7][C:6]([C:29]7[S:33][C:32]([CH3:34])=[N:31][CH:30]=7)=[C:5]([C:3]([NH:2][CH3:1])=[O:4])[C:9]=6[CH:10]=5)[CH:45]=[CH:44][C:43]=4[CH2:42][CH2:41][N:40]3[C:46]=2[CH:47]=[CH:48][CH:49]=1

参加物

9

反応物 5

HCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 90333549N-methyl-6-(N-methylmethylsulfonamido)-2-(2-methylthiazol-5-yl)-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 778457605-(11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)-2-(2-methylthiazol-5-yl)benzofuran-3-carboxamide収率 12.2%

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 N-methyl-6-(N-methylmethylsulfonamido)-2-(2-methylthiazol-5-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (200 mg, 0.40 mmol), 2-chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine (113 mg, 0.41 mmol), Na2CO3 (84 mg, 0.79 mmol), K2CO3 (109 mg, 0.79 mmol) in 1,4-dioxane (5 mL) and H2O (0.1 mL) were added Pd2(dba)3 (10 mg) and X-Phos (10 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: 12%). 1H-NMR (CDCl3, 400 MHz) δ 8.41 (s, 1H), 7.89 (s, 1H), 7.62˜7.68 (m, 2H), 7.45 (d, J=7.6 Hz, 1H), 7.24 (s, 1H), 7.12˜7.20 (m, 2H), 6.74˜6.81 (m, 1H), 6.22 (d, J=4.0 Hz, 1H), 4.32 (t, J=6.4 Hz, 2H), 3.32 (s, 3H), 3.27˜3.31 (m, 2H), 3.02 (d, J=4.8 Hz, 3H), 2.75 (s, 3H), 2.74 (s, 3H). MS (M+H)+: 616.

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-6d1042efa5844e648c25d392ae966403
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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