Ammonium Chloride → 3-(7-Chloro-2-dimethylaminomethyl-quinolin-8-yl)-4-(7-methyl-1H-indol-3-yl)-pyrrole-2,5-dione

HRID 1968733Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1968733
CC(C)([O-])C.[K+].CO[C:9](=[O:22])[C:10]([C:12]1[C:20]2[C:15](=[C:16]([CH3:21])[CH:17]=[CH:18][CH:19]=2)[NH:14][CH:13]=1)=O.[Cl:23][C:24]1[C:33]([CH2:34][C:35]([NH2:37])=[O:36])=[C:32]2[C:27]([CH:28]=[CH:29][C:30]([CH2:38][N:39]([CH3:41])[CH3:40])=[N:31]2)=[CH:26][CH:25]=1.[NH4+].[Cl-]>O1CCCC1.CCOC(C)=O>[Cl:23][C:24]1[C:33]([C:34]2[C:35](=[O:36])[NH:37][C:9](=[O:22])[C:10]=2[C:12]2[C:20]3[C:15](=[C:16]([CH3:21])[CH:17]=[CH:18][CH:19]=3)[NH:14][CH:13]=2)=[C:32]2[C:27]([CH:28]=[CH:29][C:30]([CH2:38][N:39]([CH3:40])[CH3:41])=[N:31]2)=[CH:26][CH:25]=1

Komponenten

7

Edukt 4

HCID 25517Ammonium ChlorideHCID 11241405Methyl 7-methyl-alpha-oxo-1H-indole-3-acetateHCID 23665647Potassium tert-butoxideHCID 668814632-(7-Chloro-2-dimethylaminomethyl-quinolin-8-yl)-acetamide

Produkt 1

HCID 159521733-(7-Chloro-2-dimethylaminomethyl-quinolin-8-yl)-4-(7-methyl-1H-indol-3-yl)-pyrrole-2,5-dioneAusbeute 71,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Potassium tert-butoxide (1.0 M in THF, 0.60 ml, 0.60 mmol, 3.0 equiv) was added at room temperature under an atmosphere of argon to a solution of (7-methyl-1H-indol-3-yl)-oxo-acetic acid methyl ester (65 mg, 0.30 mmol, 1.5 equiv) and of 2-(7-chloro-2-dimethylaminomethyl-quinolin-8-yl)-acetamide (55 mg, 0.20 mmol) in anhydrous tetrahydrofuran (2.0 ml, dried over molecular sieves). The reaction mixture was stirred for 15 minutes at room temperature. It was then diluted with EtOAc and poured into a saturated aqueous NH4Cl solution. After three extractions with EtOAc, the combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. Purification of the residue via preparative HPLC afforded the title compound (64 mg, 58%) as its trifluoroacetate salt. 1H NMR (400 MHz, d6-DMSO): δ=11.90 (br s, 1H), 11.18 (s, 1H), 9.72 (br s, 1H), 8.59 (d, J=8.2 Hz, 1H), 8.19 (d, J=9.2 Hz, 1H), 7.98 (d, J=2.6 Hz, 1H), 7.77 (d, J=8.8 Hz, 1H), 7.61 (d, J=8.8 Hz, 1H), 6.73 (d, J=7.3 Hz, 1H), 6.33 (t, J=7.3 Hz, 1H), 5.94 (d, J=7.3 Hz, 1H), 4.59 (s, 2H), 2.69 (br s, 6H), 2.38 (s, 3H). MS (ES+): 445.3 (M+H)+.

Aufarbeitung

  1. extractionAfter three extractions with EtOAc
  2. dry with materialthe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification of the residue via preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-6ba44c87fbee4d89b5e7bf4e706dee47
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08426440B2

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