Reaktion #1333072

Reaktionsgleichung

potassium hydroxide

2-(Ethoxymethyl)-1-[2-(benzyloxy)ethyl]-6,7-dimethyl-4-phenoxy-1H-imidazo[4,5-c]pyridine

ammonium acetate

→

1-[2-(benzyloxy)ethyl]-2-(ethoxymethyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-4-amine

Ausbeute 40.2%

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigescrew cap
2. 2
   ExtraktionThe basic solution was extracted with dichloromethane (5×)
3. 3
   Waschenwashed with water (3×) and brine (3×)
4. 4
   Trocknendried with magnesium sulfate
5. 5
   Filtrationfiltered
6. 6
   Einengenconcentrated under reduced pressure
7. 7
   SonstigeThe resulting oil was triturated with diethyl ether
8. 8
   FiltrationAfter the resulting solids were filtered off
9. 9
   Sonstigedried
10. 10
    Sonstigethey were recrystallized from ethyl acetate/diethyl ether
11. 11
    Sonstigeagain dried
12. 12
    workup.DISSOLUTIONThe recrystallized solids were dissolved in ethanol
13. 13
    workup.ADDITIONHydrochloric acid (10 mL, 1 N) was added to the ethanol solution
14. 14
    Filtrationthe resulting salt was filtered off
15. 15
    workup.DISSOLUTIONdissolved in water
16. 16
    Extraktionextracted with dichloromethane (4×)
17. 17
    Waschenwashed with water (2×) and brine (3×)
18. 18
    Trocknendried with magnesium sulfate
19. 19
    Filtrationfiltered
20. 20
    Einengenconcentrated under reduced pressure to a white solid
21. 21
    SonstigeThe white solid was dried

Vorschrift

2-(Ethoxymethyl)-1-[2-(benzyloxy)ethyl]-6,7-dimethyl-4-phenoxy-1H-imidazo[4,5-c]pyridine (4.33 g, 10.03 mmol) was placed in a glass reaction flask, and then ammonium acetate (45 g) was added. The flask was sealed with a teflon screw cap and heated to 156° C. for 44 hours. The reaction was determined to be complete by HPLC analysis, and the desired product's molecular weight was confirmed by LC/MS. The resulting solution was basified with 1 N potassium hydroxide to a pH of about 14. The basic solution was extracted with dichloromethane (5×), and the organic layers were combined, washed with water (3×) and brine (3×), dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting oil was triturated with diethyl ether. After the resulting solids were filtered off and dried, they were recrystallized from ethyl acetate/diethyl ether and again dried. NMR analysis or the recrystallized solids indicated impurities. The recrystallized solids were dissolved in ethanol. Hydrochloric acid (10 mL, 1 N) was added to the ethanol solution, and the resulting salt was filtered off and dissolved in water. The resulting aqueous solution was basified with 1 N potassium hydroxide to a pH of about 14 and extracted with dichloromethane (4×). The organic layers were combined, washed with water (2×) and brine (3×), dried with magnesium sulfate, filtered, and concentrated under reduced pressure to a white solid. The white solid was dried to provide 1.4285 g of 1-[2-(benzyloxy)ethyl]-2-(ethoxymethyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-4-amine, m.p. 107.3–108.2° C.

Quelle