Phthalimide → 2-((6-Methylpyridin-2-YL)methyl)isoindoline-1,3-dione

HRID 633118Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 633118
CC(OC(/N=N/C(OC(C)C)=O)=O)C.[CH3:15][C:16]1[N:21]=[C:20]([CH2:22]O)[CH:19]=[CH:18][CH:17]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:43]1(=[O:53])[C:51]2[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=2)[C:45](=[O:52])[NH:44]1>C1COCC1>[CH3:15][C:16]1[N:21]=[C:20]([CH2:22][N:44]2[C:45](=[O:52])[C:46]3[C:51](=[CH:50][CH:49]=[CH:48][CH:47]=3)[C:43]2=[O:53])[CH:19]=[CH:18][CH:17]=1

Komponenten

6

Edukt 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 707366-Methyl-2-pyridylmethanolHCID 5363146Diisopropyl azodicarboxylate

Produkt 1

HCID 668962932-((6-Methylpyridin-2-YL)methyl)isoindoline-1,3-dione

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

2.5 mL of Diisopropylazodicarboxylate in 1.5 mL of THF was added dropwise to a solution of 250 mg of (6-methylpyridin-2-yl)methanol, 2.8 g of Triphenylphosphine and 1.6 g of isoindoline-1,3-dione in anhydrous THF at room temperature. The reaction was stirred for 2 hours and monitored by TLC. Upon complection, the solvent was concentrated, the crude material was extracted in water and Chloroform 3 times and dried over Magnesium Sulfate. The crude was purified via ISCO Combi-Flash to yield 2-((6-methylpyridin-2-yl)methyl)isoindoline-1,3-dione. 350 mg of 2-((6-methylpyridin-2-yl)methyl)isoindoline-1,3-dione was treated with 440 μL of Hydrazine Monohydrate in EtOH and refluxed for several hours to yield (6-methylpyridin-2-yl)methanamine. The crude (6-methylpyridin-2-yl)methanamine was evaporated and directly coupled to 50 mg of 3-chloro-4-(4-chloro-3-(pyridin-2-yl)phenylcarbamoyl)benzoic acid via Procedure G. The crude product was purified on reverse phase HPLC to yield 2-chloro-N1-(4-chloro-3-(pyridin-2-yl)phenyl)-N4-((6-methylpyridin-2-yl)methyl)terephthalamide. MS (Q1) 491.1 (M)+.

Aufarbeitung

  1. concentrationUpon complection, the solvent was concentrated
  2. extractionthe crude material was extracted in water
  3. dry with materialChloroform 3 times and dried over Magnesium Sulfate
  4. customThe crude was purified via ISCO Combi-Flash

Quellen und Nachweise

ORD-Eintrag
ord-2cd342625e934c58a64750c4c92b56db
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09321761B2

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