반응 #46250

반응 방정식

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

용매

pyridine

pyridine

반응 조건

후처리

1. 1
   workup.STIRRINGstirred at rt for an additional 3 h
2. 2
   온도The reaction was cooled to 0° C.
3. 3
   기타quenched with 2M NH3 in i-PrOH (10 mL )
4. 4
   workup.STIRRINGstirred for an additional 30 min at rt
5. 5
   여과The mixture was filtered through a fritted funnel
6. 6
   농축the filtrate was concentrated in vacuo
7. 7
   기타partitioned between CHCl3 and H2O
8. 8
   기타separated
9. 9
   추출The aqueous layer was re-extracted with CHCl3 (3×)
10. 10
    세척the combined CHCl3 fractions were washed with brine (1×)
11. 11
    건조dried over Na2SO4
12. 12
    여과filtered
13. 13
    농축concentrated in vacuo
14. 14
    기타the crude material was chromatographed on silica gel [eluting with 2% MEOH in CHCl3]
15. 15
    기타resulting in a dark brown oil which
16. 16
    기타was crystallized from EtOAc/hexanes

실험 절차

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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