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

HRID 1811086노트

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HRID 1811086 반응식
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

참가 물질

5

반응물 3

HCID 10340Sodium CarbonateHCID 467380052-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline2회HCID 468335224-bromo-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide

생성물 1

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

시약·촉매·용매 1

HCID 882672-Methylphenethyl alcohol용매

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-b3a70844f4454448b0fb940e0b83208f
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08362065B2

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