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

HRID 595572
ノート
印刷プレビュー

反応式

HRID 595572 の反応式
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:10][C:11]3[CH:21]=[C:20]([N:22]([CH3:27])[S:23]([CH3:26])(=[O:25])=[O:24])[C:19](B4OC(C)(C)C(C)(C)O4)=[CH:18][C:12]=3[C:13]=2[C:14]([NH:16][CH3:17])=[O:15])=[CH:5][CH:4]=1)#[N:2].Cl[C:38]1[CH:39]=[CH:40][C:41]2[O:54][CH2:53][N:44]3[C:45]4[CH:46]=[CH:47][CH:48]=[C:49]([F:52])[C:50]=4[CH:51]=[C:43]3[C:42]=2[N:55]=1.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]>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:10][C:11]3[CH:21]=[C:20]([N:22]([CH3:27])[S:23]([CH3:26])(=[O:25])=[O:24])[C:19]([C:38]4[CH:39]=[CH:40][C:41]5[O:54][CH2:53][N:44]6[C:45]7[CH:46]=[CH:47][CH:48]=[C:49]([F:52])[C:50]=7[CH:51]=[C:43]6[C:42]=5[N:55]=4)=[CH:18][C:12]=3[C:13]=2[C:14]([NH:16][CH3:17])=[O:15])=[CH:5][CH:4]=1)#[N:2]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 867283052-chloro-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indoleHCID 903338432-(4-cyanophenyl)-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 903337362-(4-cyanophenyl)-5-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide
収率 21.9%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 218864351,4-Dioxane--water (1/1)溶媒

実験手順

To a solution of 2-(4-cyanophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (115 mg, 0.22 mmol), 2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (75 mg, 0.27 mmol) K2CO3 (60 mg, 0.44 mmol), Pd2(dba)3 (30 mg) and X-Phos (30 mg) in dioxane/H2O (3 mL/0.6 mL) was stirred at 100° C. for 3 h. The reaction was filtered to remove the solid and then the mixture was diluted with water and extracted with EA. The organic layer was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by prep-HPLC to get the product of 2-(4-cyanophenyl)-5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (30 mg, yield: 21%). 1H-NMR (CDCl3, 400 MHz) δ 8.16 (d, J=8.4 Hz, 2H), 7.96 (s, 1H), 7.78 (d, J=8.4 Hz, 2H), 7.70 (s, 1H), 7.23˜7.19 (m, 3H), 7.13 (d, J=8.4 Hz, 2H), 6.87 (m, 1H), 6.14 (d, J=4.4 Hz, 1H), 6.00 (s, 2H), 3.35 (s, 3H), 3.05 (d, J=5.2 Hz, 3H), 2.77 (s, 3H). MS (M+H)+: 622.

後処理

  1. filtrationThe reaction was filtered
  2. customto remove the solid
  3. additionthe mixture was diluted with water
  4. extractionextracted with EA
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by prep-HPLC

出典と根拠

ORDレコード
ord-9a6bfcbb1d4549e499ac77059abfa3c9
出典データセット
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09242998B2

反応ノート

読み込み中…

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