Dimethylformamide → 7-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine

HRID 62477Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 62477
O=P(Cl)(Cl)Cl.[Cl:6][C:7]1[C:8]([CH2:13][NH:14][C:15]([CH:17]2[CH2:22][CH2:21][N:20]3[C:23]([C:26]([F:29])([F:28])[F:27])=[N:24][N:25]=[C:19]3[CH2:18]2)=O)=[N:9][CH:10]=[CH:11][N:12]=1.CN(C=O)C.C([O-])([O-])=O.[Na+].[Na+]>CC#N>[Cl:6][C:7]1[C:8]2[N:9]([C:15]([CH:17]3[CH2:22][CH2:21][N:20]4[C:23]([C:26]([F:29])([F:28])[F:27])=[N:24][N:25]=[C:19]4[CH2:18]3)=[N:14][CH:13]=2)[CH:10]=[CH:11][N:12]=1

Komponenten

6

Edukt 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 90303325N-((3-chloropyrazin-2-yl)methyl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-7-carboxamide

Produkt 1

HCID 903040007-(8-Chloroimidazo[1,5-a]pyrazin-3-yl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridineAusbeute 44,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

POCl3 (1.7 g, 11.09 mmol) was added dropwise to a solution of N-((3-chloropyrazin-2-yl)methyl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-7-carboxamide (800 mg, 2.218 mmol) in CH3CN (4.4 mL) at 0° C., then DMF (0.11 mL) was added dropwise for 5 minutes at 0° C. The reaction was heated at 70° C. for overnight The reaction was poured into ice-water, then neutralized with aq. Na2CO3 to adjust to pH=8. The resulting mixture was extracted with DCM and the combined organic layer was washed with water, brine and dried over anhydrous Na2SO4. The organic layer was concentrated in vacuo and the residue was purified by silica gel column chromatography (DCM/THF=100/20) to afford 7-(8-chloroimidazo[1,5-a]pyrazin-3-yl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine (0.34 g, yield 44%).

Aufarbeitung

  1. extractionThe resulting mixture was extracted with DCM
  2. washthe combined organic layer was washed with water, brine
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationThe organic layer was concentrated in vacuo
  5. customthe residue was purified by silica gel column chromatography (DCM/THF=100/20)

Quellen und Nachweise

ORD-Eintrag
ord-10baf883f2284b12ab50ea83528e820f
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09446130B2

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