(2-{[3-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-methyl-butyrylamino]-methyl}-pyridin-3-yloxy)-acetic acid ethyl ester → {3-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-2-methyl-propyl]-imidazo[1,5-a]pyridin-8-yloxy}-acetic acid ethyl ester

HRID 1271553Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1271553
[CH2:1]([O:3][C:4](=[O:32])[CH2:5][O:6][C:7]1[C:8]([CH2:13][NH:14][C:15](=O)[CH2:16][C:17]([N:20]2[C:28](=[O:29])[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21]2=[O:30])([CH3:19])[CH3:18])=[N:9][CH:10]=[CH:11][CH:12]=1)[CH3:2]>P(Cl)(Cl)(Cl)=O>[CH2:1]([O:3][C:4](=[O:32])[CH2:5][O:6][C:7]1[C:8]2[N:9]([C:15]([CH2:16][C:17]([N:20]3[C:28](=[O:29])[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[C:21]3=[O:30])([CH3:19])[CH3:18])=[N:14][CH:13]=2)[CH:10]=[CH:11][CH:12]=1)[CH3:2]

Komponenten

3

Edukt 1

HCID 69158493(2-{[3-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-methyl-butyrylamino]-methyl}-pyridin-3-yloxy)-acetic acid ethyl ester

Produkt 1

HCID 69157841{3-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-2-methyl-propyl]-imidazo[1,5-a]pyridin-8-yloxy}-acetic acid ethyl esterAusbeute 55,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 24813Phosphorus oxychlorideLösungsmittel

Versuchsvorschrift

A solution of (2-{[3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-methyl-butyrylamino]-methyl}-pyridin-3-yloxy)-acetic acid ethyl ester (2.79 g, 6.349 mmol) in 100 ml of neat phosphoryl chloride is stirred at 75° C. for 16 hours. The reaction mixture is poured on 200 g of crushed ice and extracted with methylene chloride. The organic phase is dried over sodium sulfate and evaporated. The residue is purified via flash chromatography on silica gel using a methylene chloride/methylene chloride-ethanolic ammonia gradient (100 to 96:4) to give 1.48 g of {3-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-methyl-propyl]-imidazo[1,5-a]pyridin-8-yloxy}-acetic acid ethyl ester (55%).

Aufarbeitung

  1. extractionextracted with methylene chloride
  2. dry with materialThe organic phase is dried over sodium sulfate
  3. customevaporated
  4. customThe residue is purified via flash chromatography on silica gel using a methylene chloride/methylene chloride-ethanolic ammonia gradient (100 to 96:4)

Quellen und Nachweise

ORD-Eintrag
ord-f8a63fbf8e76481aaceb341995ad2dc5
Quelldatensatz
uspto-grants-2007_04
Patentnummer
US07205407B2

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