Ammonium Chloride → 3-(6-Dimethylaminomethyl-2-methyl-indolizin-3-yl)-4-(1H-indol-3-yl)-pyrrole-2,5-dione

HRID 402882

Reaktionsgleichung

Reaktionsgleichung von HRID 402882
CC(C)([O-])C.[K+].CO[C:9](=[O:21])[C:10]([C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:14][CH:13]=1)=O.[CH3:22][N:23]([CH2:25][C:26]1[CH:34]=[CH:33][C:32]2[N:28]([C:29]([CH2:36][C:37]([NH2:39])=[O:38])=[C:30]([CH3:35])[CH:31]=2)[CH:27]=1)[CH3:24].[NH4+].[Cl-]>O1CCCC1.CCOC(C)=O>[CH3:22][N:23]([CH2:25][C:26]1[CH:34]=[CH:33][C:32]2[N:28]([C:29]([C:36]3[C:37](=[O:38])[NH:39][C:9](=[O:21])[C:10]=3[C:12]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[NH:14][CH:13]=3)=[C:30]([CH3:35])[CH:31]=2)[CH:27]=1)[CH3:24]

Komponenten

7

Edukt 4

HCID 25517Ammonium ChlorideHCID 588944Methyl 3-indoleglyoxylateHCID 23665647Potassium tert-butoxideHCID 591920212-(6-Dimethylaminomethyl-2-methyl-indolizin-3-yl)-acetamide

Produkt 1

HCID 249682373-(6-Dimethylaminomethyl-2-methyl-indolizin-3-yl)-4-(1H-indol-3-yl)-pyrrole-2,5-dioneAusbeute 6,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Potassium tert-butoxide (1.0 M in THF, 0.24 ml, 0.24 mmol, 3.0 equiv) is added dropwise at room temperature under an atmosphere of argon to a solution of (1H-indol-3-yl)-oxo-acetic acid methyl ester (19.2 mg, 0.090 mmol, 1.1 equiv) and of 2-(6-dimethylaminomethyl-2-methyl-indolizin-3-yl)-acetamide (20 mg, 0.08 mmol) in anhydrous tetrahydrofuran (1.0 ml, dried over molecular sieves). The reaction mixture is stirred for 30 minutes at room temperature. It is then diluted with EtOAc and poured into a saturated aqueous NH4Cl solution. After three extractions with EtOAc, the combined organic layers are dried over Na2SO4, filtered and concentrated in vacuo. Purification of the residue via preparative HPLC affords the title compound (2 mg, 6%) as its trifluoroacetate salt. 1H NMR (400 MHz, d6-DMSO): δ=11.78 (s, 1H), 10.91 (s, 1H), 9.51 (s, 1H), 8.33 (s, 1H), 7.99 (d, J=2.9 Hz, 1H), 7.54 (s, 1H), 7.35 (d, J=8.1 Hz, 1H), 7.03 (d, J=9.1 Hz, 1H), 6.95 (dt, J=8.0/1.2 Hz, 1H), 6.61 (dd, J=9.3/1.3 Hz, 1H), 6.52 (dt, J=8.1/1.0 Hz, 1H), 6.17 (d, J=8.0 Hz, 1H), 4.13 (s, 2H), 2.67 (s, 6H), 1.93 (s, 3H). MS (ES+): 399 (M+H)+.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-0c708c0ac9eb42728a776ade3dc5e450
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08742132B2

Verknüpfte Notizen

Wird geladen…