Sodium Carbonate → 5-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(6-(4-fluorophenoxyl)pyridin-3-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595566ノート

反応式

HRID 595566 の反応式
[F:1][C:2]1[CH:42]=[CH:41][C:5]([O:6][C:7]2[N:12]=[CH:11][C:10]([C:13]3[O:14][C:15]4[CH:25]=[C:24]([N:26]([CH3:31])[S:27]([CH3:30])(=[O:29])=[O:28])[C:23](B5OC(C)(C)C(C)(C)O5)=[CH:22][C:16]=4[C:17]=3[C:18]([NH:20][CH3:21])=[O:19])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.Cl[C:44]1[CH:45]=[CH:46][C:47]2[O:60][CH2:59][N:50]3[C:51]4[CH:52]=[CH:53][CH:54]=[C:55]([F:58])[C:56]=4[CH:57]=[C:49]3[C:48]=2[N:61]=1.C([O-])([O-])=O.[Na+].[Na+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>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:58][C:55]1[C:56]2[CH:57]=[C:49]3[C:48]4[N:61]=[C:44]([C:23]5[C:24]([N:26]([CH3:31])[S:27]([CH3:30])(=[O:28])=[O:29])=[CH:25][C:15]6[O:14][C:13]([C:10]7[CH:11]=[N:12][C:7]([O:6][C:5]8[CH:41]=[CH:42][C:2]([F:1])=[CH:3][CH:4]=8)=[CH:8][CH:9]=7)=[C:17]([C:18]([NH:20][CH3:21])=[O:19])[C:16]=6[CH:22]=5)[CH:45]=[CH:46][C:47]=4[O:60][CH2:59][N:50]3[C:51]=2[CH:52]=[CH:53][CH:54]=1

参加物

7

反応物 4

HCID 10340Sodium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 867283052-chloro-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indoleHCID 903338672-(6-(4-fluorophenoxy)pyridin-3-yl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide

生成物 1

HCID 778456625-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(6-(4-fluorophenoxyl)pyridin-3-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide収率 31.4%

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 stirring mixture of 2-(6-(4-fluorophenoxy)pyridin-3-yl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (50 mg, 0.09 mmol), 2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (28 mg, 0.10 mmol) and Na2CO3 (18 mg, 0.17 mmol) in dioxane (0.8 mL) was added X-Phos (5 mg) and Pd2(dba)3 (5 mg) under N2 protection. The mixture was stirred at a pre-heated oil-bath 100° C. for 3 h. The mixture was concentrated and the residue was extracted with EA. The residue was washed with H2O, brine and dried over Na2SO4. After concentrated, the crude product was purified by prep-HPLC to give the product of 5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(6-(4-fluorophenoxy)pyridin-3-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (20 mg, yield: 30%). 1H-NMR (CDCl3, 400 MHz) δ 8.70 (d, J=2.0 Hz, 1H), 8.31˜8.34 (m, 1H), 7.91 (s, 1H), 7.62 (s, 1H), 7.44 (s, 2H), 7.15 (s, 2H), 7.04˜7.10 (m, 5H), 6.98 (d, J=8.8 Hz, 1H), 6.76˜6.81 (m, 1H), 5.94 (s, 2H), 5.90 (d, J=8.8 Hz, 1H), 3.30 (s, 3H), 2.96 (d, J=4.8 Hz, 3H), 2.70 (s, 3H). MS (M+H)+: 708.

後処理

  1. concentrationThe mixture was concentrated
  2. extractionthe residue was extracted with EA
  3. washThe residue was washed with H2O, brine
  4. dry with materialdried over Na2SO4
  5. concentrationAfter concentrated
  6. customthe crude product was purified by prep-HPLC

出典と根拠

ORDレコード
ord-26203b2ac18c458dbb8490064ad3aa33
出典データセット
uspto-grants-2016_01
特許番号
US09242998B2

反応ノート

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