Dimethylformamide → 8-Chloro-3-(methylsulfanyl)imidazo[1,5-A]pyrazine

HRID 449009Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 449009
[CH3:1][S:2][C:3](=O)[NH:4][CH2:5][C:6]1[C:11]([Cl:12])=[N:10][CH:9]=[CH:8][N:7]=1.CN(C=O)C.O=P(Cl)(Cl)Cl>CC#N>[Cl:12][C:11]1[C:6]2[N:7]([C:3]([S:2][CH3:1])=[N:4][CH:5]=2)[CH:8]=[CH:9][N:10]=1

Komponenten

5

Edukt 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 59130384(3-chloro-pyrazin-2-ylmethyl)-thiocarbamic acid S-methyl ester

Produkt 1

HCID 591303828-Chloro-3-(methylsulfanyl)imidazo[1,5-A]pyrazineAusbeute 63 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

To a solution of (3-chloro-pyrazin-2-ylmethyl)-thiocarbamic acid S-methyl ester (3.05 g, 0.0140 mol) in MeCN (70 mL) were added DMF (4.3 mL, 0.056 mol) and POCl3 (5.2 mL, 0.056 mol) at 0° C. under nitrogen. The reaction mixture was slowly warmed to rt and stirred at rt overnight. LC-MS showed the SM was completely consumed. The solvent was evaporated under reduced pressure and the residue was cooled at 0° C. and diluted with EtOAc (250 mL), then quenched with sat. aq. NaHCO3 (100 mL). The mixture was washed brine (50 mL), and dried over anhydrous sodium sulfate. The crude material was purified by silica gel chromatography (Hexane EtOAc=80:20→70:30) to give the title compound as a light-yellow solid, 1.75 g, 63% yield. LC-MS (ES+): 200/202 (3/1) [MH+], and 1H NMR (CDCl3, 400 MHz): δ 2.71 (s, 3H), 7.40 (d, J=5.1 Hz, 1H), 7.74 (dd, J=5.1, 1.0 Hz, 1H), 7.90 (s, 1H).

Aufarbeitung

  1. customwas completely consumed
  2. customThe solvent was evaporated under reduced pressure
  3. temperaturethe residue was cooled at 0° C.
  4. additiondiluted with EtOAc (250 mL)
  5. customquenched with sat. aq. NaHCO3 (100 mL)
  6. washThe mixture was washed brine (50 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe crude material was purified by silica gel chromatography (Hexane EtOAc=80:20→70:30)

Quellen und Nachweise

ORD-Eintrag
ord-0c6f8055a2bb4426bb119af9d1a91e00
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08481733B2

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