Diisopropylethylamine → 2-[2-Hydroxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-7-methyl-3H-benzimidazole-5-carboxylic acid {4-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenyl}-amide

HRID 470359Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 470359
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([O:14][CH3:15])=[N:10][CH:11]=[CH:12][CH:13]=2)=[CH:4][C:3]=1[C:16]1[NH:17][C:18]2[CH:24]=[C:23]([C:25]([OH:27])=O)[CH:22]=[C:21]([CH3:28])[C:19]=2[N:20]=1.[CH3:29][N:30]1[CH2:35][CH2:34][N:33]([CH2:36][CH2:37][C:38]2[CH:43]=[CH:42][C:41]([NH2:44])=[CH:40][CH:39]=2)[CH2:32][CH2:31]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:29][N:30]1[CH2:35][CH2:34][N:33]([CH2:36][CH2:37][C:38]2[CH:39]=[CH:40][C:41]([NH:44][C:25]([C:23]3[CH:22]=[C:21]([CH3:28])[C:19]4[N:20]=[C:16]([C:3]5[CH:4]=[C:5]([C:8]6[C:9]([O:14][CH3:15])=[N:10][CH:11]=[CH:12][CH:13]=6)[CH:6]=[CH:7][C:2]=5[OH:1])[NH:17][C:18]=4[CH:24]=3)=[O:27])=[CH:42][CH:43]=2)[CH2:32][CH2:31]1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 242554804-[2-(4-Methylpiperazin-1-yl)ethyl]anilineHCID 136106278HCID 136106278, Verbindung

Produkt 1

HCID 1361065452-[2-Hydroxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-7-methyl-3H-benzimidazole-5-carboxylic acid {4-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenyl}-amideAusbeute 15 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of the crude of 2-[2-hydroxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-7-methyl-3H-benzoimidazole-5-carboxylic acid (estimated 0.4 mmol), 4-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenylamine (88 mg, 0.4 mmol) and HATU (167 mg, 0.44 mmol) in DMF (5 mL) was added DIEA (0.5 mL, 371 mg, 2.87 mmol). The reaction mixture was stirred at room temperature for 2 h and heated at 60° C. for 15 h, and then evaporated to dry under reduced pressure. The residue was diluted with DMSO (1.5 mL), filtered and then purified with using HPLC (TFA/H2O/CH3CN) to afford the title compound (34.5 mg, 11% from two steps from 3,4-diamino-5-methyl-benzoic acid). 1H NMR (MeOH-d4) δ 2.77 (s, 3H), 2.90 (s, 3H), 2.97-3.43 (12H), 3.97 (s, 3H), 7.09 (m, 1H), 7.22 (d, J=9 Hz, 1H), 7.31 (d, J=9 Hz, 2H), 7.70 (d, J=9 Hz, 2H), 7.82-7.84 (2H), 7.91 (s, 1H), 8.17 (m, 1H), 8.20 (s, 1H), 8.31 (s, 1H). ESI-MS m/z 577.5 (MH+).

Aufarbeitung

  1. temperatureheated at 60° C. for 15 h
  2. customevaporated
  3. customto dry under reduced pressure
  4. additionThe residue was diluted with DMSO (1.5 mL)
  5. filtrationfiltered
  6. custompurified with using HPLC (TFA/H2O/CH3CN)

Quellen und Nachweise

ORD-Eintrag
ord-0419d47c64dd4c098ad5926e14d4e64a
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08629147B2

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