Reaktion #46250

Reaktionsgleichung

5-(3-benzyloxy-phenyl)-7-cyclobutyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

1,2,4-triazole

phosphorous oxychloride

→

title compound

5-(3-benzyloxy-phenyl)-7-cyclobutyl-imidazo[5,1-f][1,2,4]triazin-4-ylamine

Lösungsmittel

pyridine

pyridine

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGstirred at rt for an additional 3 h
2. 2
   TemperaturThe reaction was cooled to 0° C.
3. 3
   Sonstigequenched with 2M NH3 in i-PrOH (10 mL )
4. 4
   workup.STIRRINGstirred for an additional 30 min at rt
5. 5
   FiltrationThe mixture was filtered through a fritted funnel
6. 6
   Einengenthe filtrate was concentrated in vacuo
7. 7
   Sonstigepartitioned between CHCl3 and H2O
8. 8
   Sonstigeseparated
9. 9
   ExtraktionThe aqueous layer was re-extracted with CHCl3 (3×)
10. 10
    Waschenthe combined CHCl3 fractions were washed with brine (1×)
11. 11
    Trocknendried over Na2SO4
12. 12
    Filtrationfiltered
13. 13
    Einengenconcentrated in vacuo
14. 14
    Sonstigethe crude material was chromatographed on silica gel [eluting with 2% MEOH in CHCl3]
15. 15
    Sonstigeresulting in a dark brown oil which
16. 16
    Sonstigewas crystallized from EtOAc/hexanes

Vorschrift

To a solution of 1,2,4-triazole (167 mg, 2.417 mmol) in anhydrous pyridine (1.5 mL) was added phosphorous oxychloride (POCl3) (75 μL, 0.806 mmol) and stirred at rt for 15 min. To this mixture was added dropwise a solution of 5-(3-benzyloxy-phenyl)-7-cyclobutyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one (100 mg, 0.269 mmol) in anhydrous pyridine (2.5 mL) over a 3.5 min period and stirred at rt for an additional 3 h. The reaction was cooled to 0° C. and quenched with 2M NH3 in i-PrOH (10 mL ) and stirred for an additional 30 min at rt. The mixture was filtered through a fritted funnel and the filtrate was concentrated in vacuo, partitioned between CHCl3 and H2O and separated. The aqueous layer was re-extracted with CHCl3 (3×) and the combined CHCl3 fractions were washed with brine (1×), dried over Na2SO4, filtered and concentrated in vacuo and the crude material was chromatographed on silica gel [eluting with 2% MEOH in CHCl3] resulting in a dark brown oil which was crystallized from EtOAc/hexanes to obtain the title compound as a light tan solid. 1H NMR (CDCl3, 400 MHz) δ 1.95-2.08 (m, 1H), 2.09-2.22 (m, 1H), 2.39-2.50 (m, 2H), 2.59-2.72 (m, 2H), 4.14 (quint, J=8.4 Hz, 1H), 5.16 (s, 2H), 5.57 (brs, 2H), 7.02-7.09 (m, 1H), 7.22-7.28 (m, 3H), 7.31-7.50 (m, 5H), 7.85 (s, 1H); MS (ES+): m/z 372.1 (100) [MH+]; HPLC: tR=3.05 min (MicromassZQ, nonpolar—5 min).

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