Sodium Carbonate → 4-(3-amino-2-methylphenyl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide

HRID 1811086ノート

反応式

HRID 1811086 の反応式
Br[C:2]1[C:14]2[C:13]3[C:8](=[CH:9][C:10]([C:15]([N:17]4[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]4)=[O:16])=[CH:11][CH:12]=3)[NH:7][C:6]=2[C:5]([C:24]([NH2:26])=[O:25])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:33][C:34]1[C:40](B2OC(C)(C)C(C)(C)O2)=[CH:39][CH:38]=[CH:37][C:35]=1[NH2:36]>C1(C)C(CCO)=CC=CC=1>[NH2:36][C:35]1[C:34]([CH3:33])=[C:40]([C:2]2[C:14]3[C:13]4[C:8](=[CH:9][C:10]([C:15]([N:17]5[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]5)=[O:16])=[CH:11][CH:12]=4)[NH:7][C:6]=3[C:5]([C:24]([NH2:26])=[O:25])=[CH:4][CH:3]=2)[CH:39]=[CH:38][CH:37]=1

参加物

5

反応物 3

HCID 10340Sodium CarbonateHCID 467380052-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline2 回HCID 468335224-bromo-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide

生成物 1

HCID 468338134-(3-amino-2-methylphenyl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide収率 65%

試薬・触媒・溶媒 1

HCID 882672-Methylphenethyl alcohol溶媒

実験手順

A suspension of 4-bromo-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide (Example 1-1, 300 mg, 0.722 mmol), tetrakis-(triphenylphosphine)palladium (33.4 mg, 0.029 mmol), 2 M aqueous sodium carbonate (0.9 mL, 1.806 mmol), and 2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (Intermediate 50-1, 253 mg, 1.084 mmol) in toluene-ethanol (4:1, 15 mL) was purged with nitrogen for 5 min and then heated at reflux for 7.5 h. The mixture was concentrated and the residue was partitioned between chloroform and water. The aqueous phase was extracted with chloroform and the combined organic phases were washed with brine, dried and concentrated. The residue was purified by column chromatography (eluting with DCM-2 M methanolic ammonia, gradient from 100:0 to 95:5) to provide 4-(3-amino-2-methylphenyl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide as a white solid (207 mg, 65%). 1H NMR (400 MHz, DMSO-d6) δ 11.65 (s, 1H) 8.16 (br. s., 1H) 7.97 (d, J=7.91 Hz, 1H) 7.78 (s, 1H) 7.48 (br. s., 1H) 7.08 (t, J=7.80 Hz, 1H) 6.81-6.97 (m, 4H) 6.49-6.65 (m, 1H) 3.12-3.25 (m, 4H) 2.92-3.10 (m, 4H) 2.76 (s, 3H) 1.70 (s, 3H). Mass spectrum m/z 442.2 (M+H)+.

後処理

  1. customwas purged with nitrogen for 5 min
  2. temperatureheated
  3. temperatureat reflux for 7.5 h
  4. concentrationThe mixture was concentrated
  5. customthe residue was partitioned between chloroform and water
  6. extractionThe aqueous phase was extracted with chloroform
  7. washthe combined organic phases were washed with brine
  8. customdried
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography (eluting with DCM-2 M methanolic ammonia, gradient from 100:0 to 95:5)

出典と根拠

ORDレコード
ord-b3a70844f4454448b0fb940e0b83208f
出典データセット
uspto-grants-2013_01
特許番号
US08362065B2

反応ノート

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