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

HRID 1776920ノート

反応式

HRID 1776920 の反応式
CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.Br[C:36]1[C:37]([N:56]2[CH2:60][CH2:59][O:58][C:57]2=[O:61])=[CH:38][C:39]2[O:43][C:42]([C:44]3[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=3)=[C:41]([C:51]([NH:53][CH3:54])=[O:52])[C:40]=2[CH:55]=1.[F:62][C:63]1[C:64]2[CH:65]=[C:66]3[C:75]4[N:76]=[C:77]([Sn](C)(C)C)[CH:78]=[CH:79][C:74]=4[O:73][CH2:72][N:67]3[C:68]=2[CH:69]=[CH:70][CH:71]=1>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:62][C:63]1[C:64]2[CH:65]=[C:66]3[C:75]4[N:76]=[C:77]([C:36]5[C:37]([N:56]6[CH2:60][CH2:59][O:58][C:57]6=[O:61])=[CH:38][C:39]6[O:43][C:42]([C:44]7[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=7)=[C:41]([C:51]([NH:53][CH3:54])=[O:52])[C:40]=6[CH:55]=5)[CH:78]=[CH:79][C:74]=4[O:73][CH2:72][N:67]3[C:68]=2[CH:69]=[CH:70][CH:71]=1

参加物

6

反応物 3

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 673939695-bromo-2-(4-fluorophenyl)-N-methyl-6-(2-oxooxazolidin-3-yl)benzofuran-3-carboxamideHCID 8672829411-fluoro-2-(trimethylstannyl)-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indole

生成物 1

HCID 867282965-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(2-oxooxazolidin-3-yl)benzofuran-3-carboxamide収率 24%

試薬・触媒・溶媒 2

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

反応条件

温度
100 °C

実験手順

Pd2(dba)3 (10 mg, 0.01 mmol) and X-Phos (11 mg, 0.02 mmol) was added to the mixture of 5-bromo-2-(4-fluorophenyl)-N-methyl-6-(2-oxooxazolidin-3-yl)benzofuran-3-carboxamide (100 mg, 0.23 mmol), 11-fluoro-2-(trimethylstannyl)-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (140 mg, 0.35 mmol) in dioxane/H2O (4 mL/0.2 mL) under N2. Then the reaction mixture was heated to 100° C. for 1 hour and filtered. The resulting residue was extracted with EtOAc. The combined organic phase was dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using prep-TLC (petroleum ether:EtOAc=1:2) to provide 5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(2-oxooxazolidin-3-yl)benzofuran-3-carboxamide (32 mg, yield: 24%). 1H-NMR (CDCl3, 400 MHz) δ 8.01 (s, 1H), 7.94˜7.98 (m, 2H), 7.58 (s, 1H), 7.51 (m, 2H), 7.19˜7.23 (m, 4H), 7.11˜7.13 (d, J=8.0 Hz, 1H), 6.83˜6.88 (m, 1H), 6.12 (s, 1H), 6.00 (s, 2H), 4.37˜7.41 (m, 2H), 4.12˜4.14 (m, 2H), 3.00 (d, J=4.8 Hz, 3H). MS (M+H)+: 593.

後処理

  1. filtrationfiltered
  2. extractionThe resulting residue was extracted with EtOAc
  3. dry with materialThe combined organic phase was dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified

出典と根拠

ORDレコード
ord-b8323624b5ee422c954190297eff4b1d
出典データセット
uspto-grants-2016_02
特許番号
US09265773B2

反応ノート

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