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Hydrochloric Acid → 2-[2-({3-[4-(2-oxopyrrolidin-1-yl)phenoxy]propyl}pyridin-4-ylmethylamino)ethyl]-2H-isoquinolin-1-one dihydrochloride

HRID 1504183
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1504183
Br[C:2]1[CH:32]=[CH:31][C:5]([O:6][CH2:7][CH2:8][CH2:9][N:10]([CH2:24][C:25]2[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=2)[CH2:11][CH2:12][N:13]2[CH:22]=[CH:21][C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]2=[O:23])=[CH:4][CH:3]=1.[NH:33]1[CH2:37][CH2:36][CH2:35][C:34]1=[O:38].C(=O)([O-])[O-].[K+].[K+].CNCCNC.[ClH:51]>[Cu](I)I.C(O)C.C1(C)C=CC=CC=1>[ClH:51].[ClH:51].[O:38]=[C:34]1[CH2:35][CH2:36][CH2:37][N:33]1[C:2]1[CH:32]=[CH:31][C:5]([O:6][CH2:7][CH2:8][CH2:9][N:10]([CH2:24][C:25]2[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=2)[CH2:11][CH2:12][N:13]2[CH:22]=[CH:21][C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]2=[O:23])=[CH:4][CH:3]=1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

9

Edukt 5

HCID 313Hydrochloric AcidHCID 8070N,N'-DimethylethylenediamineHCID 11430Potassium CarbonateHCID 120252-PyrrolidoneHCID 669599672-(2-{[3-(4-Bromophenoxy)propyl]pyridin-4-ylmethylamino}ethyl)-2H-isoquinolin-1-one

Produkt 1

HCID 66960533
2-[2-({3-[4-(2-oxopyrrolidin-1-yl)phenoxy]propyl}pyridin-4-ylmethylamino)ethyl]-2H-isoquinolin-1-one dihydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 83717Copper iodideKatalysatorHCID 702EthanolLösungsmittelHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

2-(2-{[3-(4-Bromophenoxy)propyl]pyridin-4-ylmethylamino}ethyl)-2H-isoquinolin-1-one(500 mg), 2-pyrrolidone(0.228 ml), potassium carbonate(415 mg), copper iodide (I) (190 mg), and N,N′-dimethyl ethylenediamine(0.39 ml) were added to toluene(5 ml). The mixture was stirred at 100° C. for 12 hours under nitrogen atmosphere. The reaction mixture was cooled to room temperature. After adding aqueous ammonia, extraction was performed using ethyl acetate. The organic layer was washed with saturated saline, and dried with sodium sulfate. After the organic layer was condensed under reduced pressure, the residue was purified by silica gel column chromatography (ethyl acetate: methanol=100:0→70:30). The purified product was condensed under reduced pressure. A condensed hydrochloric acid(0.3 ml) was added to an ethanol solution of the residue, followed by condensation under reduced pressure. The residue was recrystallized from isopropyl alcohol/water to give the title compound(350 mg) as a white powder.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to room temperature
  2. additionAfter adding aqueous
  3. extractionammonia, extraction
  4. washThe organic layer was washed with saturated saline
  5. dry with materialdried with sodium sulfate
  6. customcondensed under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (ethyl acetate: methanol=100:0→70:30)
  8. customcondensed under reduced pressure
  9. customfollowed by condensation under reduced pressure
  10. customThe residue was recrystallized from isopropyl alcohol/water

Quellen und Nachweise

ORD-Eintrag
ord-87861d46f2ba46a181731dd1b1790dbc
Quelldatensatz
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09212187B2

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