Lithium Hexamethyldisilazide → 7-bromo-N-cyclopropyl-N-(4-methoxybenzyl)-2-(methylthio)imidazo[2,1-f][1,2,4]triazin-4-amine

HRID 1430804Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1430804
[Br:1][C:2]1[N:10]2[C:5]([C:6](SC)=[N:7][C:8]([S:11][CH3:12])=[N:9]2)=[N:4][CH:3]=1.[CH3:15][O:16][C:17]1[CH:27]=[CH:26][C:20]([CH2:21][NH:22][CH:23]2[CH2:25][CH2:24]2)=[CH:19][CH:18]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[Br:1][C:2]1[N:10]2[C:5]([C:6]([N:22]([CH:23]3[CH2:25][CH2:24]3)[CH2:21][C:20]3[CH:26]=[CH:27][C:17]([O:16][CH3:15])=[CH:18][CH:19]=3)=[N:7][C:8]([S:11][CH3:12])=[N:9]2)=[N:4][CH:3]=1

Komponenten

5

Edukt 3

HCID 2733832Lithium HexamethyldisilazideHCID 4721289N-((4-methoxyphenyl)methyl)cyclopropanamineHCID 574576447-Bromo-2,4-bis(methylthio)imidazo[2,1-f][1,2,4]triazine

Produkt 1

HCID 867084907-bromo-N-cyclopropyl-N-(4-methoxybenzyl)-2-(methylthio)imidazo[2,1-f][1,2,4]triazin-4-amineAusbeute 72,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a 25 mL flask was added a mixture of 7-bromo-2,4-bis(methylthio)imidazo[2,1-f][1,2,4]triazine (2.0 g, 6.87 mmol), N-(4-methoxybenzyl)cyclopropanamine (1.34 g, 7.56 mmol) in anhydrous THF (20 mL). The reaction solution was cooled to −78° C. and treated dropwise with 1.0 M lithium bis(trimethylsilyl)amide in THF solution (20.61 mL, 20.61 mmol, 3 eq, 1M solution in THF). The reaction was stirred at −78° C. for 1 hour, then allowed to come to room temperature and stirred for 3 hours The reaction was quenched with saturated ammonium chloride. The product was extracted with ethyl acetate, the organic layer was dried with sodium sulfate and concentrated in vacuo. The crude product mixture was purified via ISCO (0-100% of ethyl acetate/heptane in 10 minutes, 24 g silica column) to give the pure product 7-bromo-N-cyclopropyl-N-(4-methoxybenzyl)-2-(methylthio)imidazo[2,1-f][1,2,4]triazin-4-amine (2.1 g)

Aufarbeitung

  1. additionTo a 25 mL flask was added
  2. customto come to room temperature
  3. stirringstirred for 3 hours The reaction
  4. customwas quenched with saturated ammonium chloride
  5. extractionThe product was extracted with ethyl acetate
  6. dry with materialthe organic layer was dried with sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe crude product mixture was purified via ISCO (0-100% of ethyl acetate/heptane in 10 minutes, 24 g silica column)

Quellen und Nachweise

ORD-Eintrag
ord-7a1a5621a2574bd2ba679a66047b6b06
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08940736B2

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