Potassium Phosphate, Tribasic → 5-(6H-benzo[e]benzo[4,5]imidazo[1,2-c][1,3]oxazin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 1776878ノート

反応式

HRID 1776878 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[C:19]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:24])=[O:23])[C:18](C4C=CC=C(B5OC(C)(C)C(C)(C)O5)C=4)=[CH:17][C:11]=3[C:12]=2[C:13]([NH:15][CH3:16])=[O:14])=[CH:4][CH:3]=1.Cl[C:43]1[CH:44]=[CH:45][C:46]2[O:51][CH2:50][N:49]3[C:52]4[CH:58]=[CH:57][CH:56]=[CH:55][C:53]=4[N:54]=[C:48]3[C:47]=2[CH:59]=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].O>[CH:59]1[C:47]2[C:48]3[N:49]([C:52]4[CH:58]=[CH:57][CH:56]=[CH:55][C:53]=4[N:54]=3)[CH2:50][O:51][C:46]=2[CH:45]=[CH:44][C:43]=1[C:18]1[C:19]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:24])=[O:23])=[CH:20][C:10]2[O:9][C:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[C:12]([C:13]([NH:15][CH3:16])=[O:14])[C:11]=2[CH:17]=1

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 674032762-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)benzofuran-3-carboxamideHCID 712956192-chloro-6H-benzo[e]benzo[4,5]imidazo[1,2-c][1,3]oxazine

生成物 1

HCID 715095445-(6H-benzo[e]benzo[4,5]imidazo[1,2-c][1,3]oxazin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide収率 22%

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 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)benzofuran-3-carboxamide (117 mg, 0.23 mmol) and 2-chloro-6H-benzo[e]benzo[4,5]imidazo[1,2-c][1,3]oxazine (60 mg, 0.23 mmol) in dioxane:H2O (2 mL:0.5 mL) was added Pd2(dba)3 (21 mg, 0.02 mmol), X-Phos (22 mg, 0.05 mmol) and K3PO4 (184 mg, 0.69 mmol) under N2. The mixture was heated to 100° C. and stirred for about 15 hours. The reaction mixture was cooled to room temperature and filtered. The filtrate was washed with H2O, brine, dried over Na2SO4. After being concentrated in vacuo, the resulting resulting residue was purified using prep-HPLC to provide the product of Compound 133 (30 mg, yield: 22%). 1H-NMR (DMSO-d6, 400 MHz) δ 8.59 (d, J=4.4 Hz, 1H), 8.14 (d, J=1.9 Hz, 1H), 8.08˜8.05 (m, 3H), 7.77˜7.72 (m, 2H), 7.69 (s, 1H), 7.63 (dd, J=8.7, 2.0 Hz, 1H), 7.46 (t, J=8.7 Hz, 2H), 7.37˜7.30 (m, 3H), 6.38 (s, 2H), 3.21 (s, 3H), 3.05 (s, 3H), 2.87 (d, J=4.4 Hz, 3H). MS (M+H)+: 597.

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. washThe filtrate was washed with H2O, brine
  4. dry with materialdried over Na2SO4
  5. concentrationAfter being concentrated in vacuo
  6. customthe resulting resulting residue
  7. customwas purified

出典と根拠

ORDレコード
ord-c842f1995b974bd9a952a87b7e53905f
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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