Sodium Carbonate → 2-(4-(difluoromethyl)phenyl)-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 595568ノート

反応式

HRID 595568 の反応式
[F:1][CH:2]([F:37])[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.Cl[C:39]1[CH:40]=[CH:41][C:42]2[O:55][CH2:54][N:45]3[C:46]4[CH:47]=[CH:48][CH:49]=[C:50]([F:53])[C:51]=4[CH:52]=[C:44]3[C:43]=2[N:56]=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].O>[F:1][CH:2]([F:37])[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:39]4[CH:40]=[CH:41][C:42]5[O:55][CH2:54][N:45]6[C:46]7[CH:47]=[CH:48][CH:49]=[C:50]([F:53])[C:51]=7[CH:52]=[C:44]6[C:43]=5[N:56]=4)=[CH:18][C:12]=3[C:13]=2[C:14]([NH:16][CH3:17])=[O:15])=[CH:5][CH:4]=1

参加物

8

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 903335872-(4-(difluoromethyl)phenyl)-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 903339412-(4-(difluoromethyl)phenyl)-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 43%

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-(difluoromethyl)phenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (100 mg, 0.18 mmol), 2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (50 mg, 0.20 mmol), Na2CO3 (39 mg, 0.37 mmol), in 1,4-dioxane (3 mL) and H2O (0.1 mL) were added Pd2(dba)3 (5 mg) and X-Phos (5 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 being concentrated, the residue was purified by prep-HPLC to give the product of 2-(4-(difluoromethyl)phenyl)-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 (50 mg, yield: 41%). 1H-NMR (CDCl3, 400 MHz) δ 8.08 (d, J=7.6 Hz, 2H), 8.05 (s, 1H), 7.73 (s, 1H), 7.69 (d, J=8.0 Hz, 2H), 7.53 (s, 2H), 7.30 (s, 1H), 7.25 (d, J=2.8 Hz, 1H), 7.16 (d, J=8.0 Hz, 1H), 6.88˜6.93 (m, 1H), 6.75 (s, 1H), 6.09 (d, J=4.4 Hz, 1H), 6.04 (s, 2H), 3.41 (s, 3H), 3.04 (d, J=4.8 Hz, 3H), 2.79 (s, 3H). MS (M+H)+: 647.

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 being concentrated
  6. customthe residue was purified by prep-HPLC

出典と根拠

ORDレコード
ord-1e727269b23f466c912bc3585d3f90b9
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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