Triethylamine → 3-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]-phenyl]-4-[2-(4-pyridyl)-1H-benzimidazol-4-yl]carbonylamino-benzamide trihydrochloride

HRID 1533800Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1533800
[NH2:1][C:2]1[CH:33]=[CH:32][C:5]([C:6]([N:8]([CH3:31])[C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][C:10]=2[O:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([N:24]2[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]2)=[O:23])=[O:7])=[CH:4][C:3]=1[O:34][CH3:35].C(N(CC)CC)C.[N:43]1[CH:48]=[CH:47][C:46]([C:49]2[NH:53][C:52]3[CH:54]=[CH:55][CH:56]=[C:57]([C:58]([Cl:60])=[O:59])[C:51]=3[N:50]=2)=[CH:45][CH:44]=1>ClCCl>[ClH:60].[ClH:60].[ClH:60].[CH3:35][O:34][C:3]1[CH:4]=[C:5]([CH:32]=[CH:33][C:2]=1[NH:1][C:58]([C:57]1[C:51]2[N:50]=[C:49]([C:46]3[CH:47]=[CH:48][N:43]=[CH:44][CH:45]=3)[NH:53][C:52]=2[CH:54]=[CH:55][CH:56]=1)=[O:59])[C:6]([N:8]([CH3:31])[C:9]1[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][C:10]=1[O:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([N:24]1[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]1)=[O:23])=[O:7]

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 183548532-(4-pyridyl)-1H-benzimidazole-4-carbonyl chlorideHCID 183549064-amino-3-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]phenyl]benzamide

Produkt 1

HCID 220125093-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]-phenyl]-4-[2-(4-pyridyl)-1H-benzimidazol-4-yl]carbonylamino-benzamide trihydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a solution of 2-(4-pyridyl)-1H-benzimidazole-4-carboxylic acid (155 mg) in dichloromethane (2 ml) was added oxalyl chloride (0.056 ml) and N,N-dimethylformamide (2 drops) and stirred at ambient temperature for 2 hours. The reaction mixture was concentrated in vacuo to give 2-(4-pyridyl)-1H-benzimidazole-4-carbonyl chloride. To a solution of 4-amino-3-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]phenyl]benzamide (76.8 mg) and triethylamine (65 mg) in dichloromethane (5 ml) was added 2-(4-pyridyl)-1H-benzimidazole-4-carbonyl chloride in dichloromethane (2 ml) under ice bath cooling and stirred at ambient temperature for 6 hours. After the reaction mixture was concentrated in vacuo, the residue was diluted with chloroform and saturated sodium hydrogen carbonate aqueous solution. The organic layer was separated and washed with brine. The solution was dried over magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel (Chromatorex, Fuji Silysia Chemical Ltd.) column chromatography (methanol:chloroform=1:49). To the purified product was added water and 1N hydrochloric acid (0.51 ml). The solution was lyophilized to give 3-methoxy-N-methyl-N-[4-methyl-2-[5-(4-methylpiperazin-1-yl)carbonylpent-1-yloxy]-phenyl]-4-[2-(4-pyridyl)-1H-benzimidazol-4-yl]carbonylamino-benzamide trihydrochloride (120 mg).

Aufarbeitung

  1. temperaturecooling
  2. concentrationAfter the reaction mixture was concentrated in vacuo
  3. additionthe residue was diluted with chloroform and saturated sodium hydrogen carbonate aqueous solution
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialThe solution was dried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel (Chromatorex, Fuji Silysia Chemical Ltd.) column chromatography (methanol:chloroform=1:49)
  9. additionTo the purified product was added water and 1N hydrochloric acid (0.51 ml)

Quellen und Nachweise

ORD-Eintrag
ord-44052c1c44b64b94aac368cc04325ebf
Quelldatensatz
uspto-grants-2001_03
Patentnummer
US06207693B1

Notizen zur Reaktion

Wird geladen…