Triethylamine → N-[2-[4-[2-[4-(2,4-Dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl]ethyl]nicotinamide dihydrochloride

HRID 412372

Reaktionsgleichung

Reaktionsgleichung von HRID 412372
[ClH:1].Cl.[NH2:3][CH2:4][CH2:5][C:6]1[CH:38]=[CH:37][C:9]([O:10][C:11]2[CH:12]=[CH:13][C:14]3[N:18]=[C:17]([CH2:19][O:20][C:21]4[CH:34]=[CH:33][C:24]([CH2:25][CH:26]5[S:30][C:29](=[O:31])[NH:28][C:27]5=[O:32])=[CH:23][CH:22]=4)[N:16]([CH3:35])[C:15]=3[CH:36]=2)=[CH:8][CH:7]=1.C(N(CC)CC)C.Cl.[C:47](N)(=[O:54])[C:48]1[CH:53]=[CH:52][CH:51]=[N:50][CH:49]=1>CN(C)C=O>[ClH:1].[ClH:1].[O:31]=[C:29]1[NH:28][C:27](=[O:32])[CH:26]([CH2:25][C:24]2[CH:33]=[CH:34][C:21]([O:20][CH2:19][C:17]3[N:16]([CH3:35])[C:15]4[CH:36]=[C:11]([O:10][C:9]5[CH:8]=[CH:7][C:6]([CH2:5][CH2:4][NH:3][C:47](=[O:54])[C:48]6[CH:53]=[CH:52][CH:51]=[N:50][CH:49]=6)=[CH:38][CH:37]=5)[CH:12]=[CH:13][C:14]=4[N:18]=3)=[CH:22][CH:23]=2)[S:30]1

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 914083-Pyridinecarboxamide, hydrochloride (1:1)HCID 865877735-[4-[6-[4-(2-aminoethyl)phenoxy]-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione dihydrochloride

Produkt 1

HCID 18537657N-[2-[4-[2-[4-(2,4-Dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl]ethyl]nicotinamide dihydrochlorideAusbeute 84,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A mixture of 5-[4-[6-[4-(2-aminoethyl)phenoxy]-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione dihydrochloride (0.3 g), triethylamine (0.17 g) and anhydrous N,N-dimethylformamide (15 ml) was stirred at room temperature for 30 minutes. To the mixture was added nicotinamide hydrochloride (0.1 g) and this mixture was irradiated with ultrasound for 30 minutes, stirred at room temperature for 6 hours and then allowed to stand overnight. The reaction mixture was concentrated and partitioned between a mixture of ethyl acetate:tetrahydrofuran (1:1) and water. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by liquid chromatography (LiChroprepDIOL (MERCK)) using ethyl acetate:tetrahydrofuran=3:1 as the eluant. To a solution of the glassy product in tetrahydrofuran (5 ml) was added 4N hydrogen chloride in 1,4-dioxane (5 ml) and the mixture was irradiated with ultrasound for 30 minutes. The precipitate was isolated by filtration to afford the title compound (0.15 g, pale yellow powder, mp 176-180° C. (dec)).

Aufarbeitung

  1. customthis mixture was irradiated with ultrasound for 30 minutes
  2. stirringstirred at room temperature for 6 hours
  3. waitto stand overnight
  4. concentrationThe reaction mixture was concentrated
  5. custompartitioned between a mixture of ethyl acetate:tetrahydrofuran (1:1) and water
  6. washThe extract was washed with saturated aqueous sodium chloride solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by liquid chromatography (LiChroprepDIOL (MERCK))
  10. additionTo a solution of the glassy product in tetrahydrofuran (5 ml) was added 4N hydrogen chloride in 1,4-dioxane (5 ml)
  11. customthe mixture was irradiated with ultrasound for 30 minutes
  12. customThe precipitate was isolated by filtration

Quellen und Nachweise

ORD-Eintrag
ord-f9cb5a19f9904611a24eb76853a4721a
Quelldatensatz
uspto-grants-2003_05
Patentnummer
US06562849B1

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