1-Hydroxybenzotriazole → 2,3-Dihydrobenzofuran-7-carboxylic acid methyl-(2-{[3-(1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yloxy)propyl]pyridin-4-ylmethylamino}ethyl)amide dihydrochloride

HRID 69011

Reaktionsgleichung

Reaktionsgleichung von HRID 69011
[ClH:1].CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.Cl.Cl.Cl.[CH3:26][NH:27][CH2:28][CH2:29][N:30]([CH2:46][C:47]1[CH:52]=[CH:51][N:50]=[CH:49][CH:48]=1)[CH2:31][CH2:32][CH2:33][O:34][C:35]1[CH:36]=[C:37]2[C:42](=[CH:43][CH:44]=1)[C:41](=[O:45])[NH:40][CH2:39][CH2:38]2.[O:53]1[C:57]2[C:58]([C:62](O)=[O:63])=[CH:59][CH:60]=[CH:61][C:56]=2[CH2:55][CH2:54]1.C(OC(=O)C)C.Cl>C(OCC)(=O)C.O.CN(C=O)C>[ClH:1].[ClH:1].[CH3:26][N:27]([CH2:28][CH2:29][N:30]([CH2:31][CH2:32][CH2:33][O:34][C:35]1[CH:36]=[C:37]2[C:42](=[CH:43][CH:44]=1)[C:41](=[O:45])[NH:40][CH2:39][CH2:38]2)[CH2:46][C:47]1[CH:48]=[CH:49][N:50]=[CH:51][CH:52]=1)[C:62]([C:58]1[C:57]2[O:53][CH2:54][CH2:55][C:56]=2[CH:61]=[CH:60][CH:59]=1)=[O:63]

Komponenten

9

Edukt 5

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27950142,3-Dihydro-1-benzofuran-7-carboxylic acidHCID 21866389Hydrogen chloride-ethyl acetateHCID 669612116-{3-[(2-methylaminoethyl)pyridin-4-ylmethylamino]propoxy}-3,4-dihydro-2H-isoquinolin-1-one trihydrochloride

Produkt 1

HCID 867626802,3-Dihydrobenzofuran-7-carboxylic acid methyl-(2-{[3-(1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yloxy)propyl]pyridin-4-ylmethylamino}ethyl)amide dihydrochlorideAusbeute 74,6 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (WSC)(144 mg), and 1-hydroxy benzotriazole (HOBt)(115 mg) were added to a DMF solution (5 ml) of 6-{3-[(2-methylaminoethyl)pyridin-4-ylmethylamino]propoxy}-3,4-di hydro-2H-isoquinolin-1-one trihydrochloride (234 mg), and 2,3-dihydrobenzofuran-7-carboxylic acid (123 mg). The mixture was stirred at room temperature overnight. Water was added to the reaction mixture, followed by extraction using ethyl acetate. The organic layer was washed with water, and dried with anhydrous sodium sulfate. After condensation under reduced pressure, the residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=1:0→10:1). The purified product was condensed under reduced pressure. A 4N-hydrogen chloride ethyl acetate solution (0.19 ml) was added to an ethyl acetate solution of the residue. The precipitated insoluble matter was separated, washed with ethyl acetate, and dried to give the title compound (164.6 mg) as a white powder.

Aufarbeitung

  1. extractionfollowed by extraction
  2. washThe organic layer was washed with water
  3. dry with materialdried with anhydrous sodium sulfate
  4. customAfter condensation under reduced pressure
  5. customthe residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=1:0→10:1)
  6. customcondensed under reduced pressure
  7. customThe precipitated insoluble matter was separated
  8. washwashed with ethyl acetate
  9. customdried

Quellen und Nachweise

ORD-Eintrag
ord-3ed03c937910480798e2baa42c6f8684
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822453B2

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