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

HRID 661905Notes

Reaction equation

HRID 661905 reaction equation
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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 882672-Methylphenethyl alcoholSolvent

Procedure

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)+.

Workup

  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)

Sources & evidence

ORD record
ord-3fb5746628f9434f9f161a94ffbde099
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

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