Reaktion #11473

Reaktionsgleichung

N-{2-[(3-amino-5,6-dimethyl-2-phenoxypyridin-4-yl)amino]-1,1-dimethylethyl}acetamide

triethylamine

ethoxyacetyl chloride

→

N-{2-[2-(ethoxymethyl)-6,7-dimethyl-4-phenoxy-1H-imidazo[4,5-c]pyridin-1-yl]-1,1-dimethylethyl}acetamide

Ausbeute 45.6%

Lösungsmittel

CH2Cl2

Reaktionsbedingungen

Aufarbeitung

1. 1
   Einengenthe reaction mixture was concentrated under reduced pressure
2. 2
   workup.ADDITIONtreated with 3 mL of triethylamine
3. 3
   TemperaturThe solution was heated
4. 4
   Temperaturto reflux for 4 d
5. 5
   EinengenThe reaction mixture was then concentrated
6. 6
   workup.DISSOLUTIONredissolved in 50 mL of xylenes
7. 7
   workup.ADDITIONtreated with pyridinium hydrochloride (0.5 g)
8. 8
   Temperaturthe mixture was heated
9. 9
   Temperaturto reflux for 4 d
10. 10
    EinengenThe reaction mixture was concentrated
11. 11
    Waschenwashed with saturated NaHCO3 solution, H2O (2×) and brine
12. 12
    TrocknenThe organic portion was dried over Na2SO4
13. 13
    Einengenconcentrated
14. 14
    SonstigeThe resulting syrup was purified by column chromatography (SiO2, 80% EtOAc/hexanes)

Vorschrift

A solution of N-{2-[(3-amino-5,6-dimethyl-2-phenoxypyridin-4-yl)amino]-1,1-dimethylethyl}acetamide (1.80 g, 5.23 mmol) in 50 mL of CH2Cl2 was cooled to 0° C., under N2, and treated with triethylamine (728 μL, 5.23 mmol) and ethoxyacetyl chloride (574 μL, 5.23 mmol). After stirring overnight, the reaction mixture was concentrated under reduced pressure. The resulting syrup was taken up in 50 mL of EtOH and treated with 3 mL of triethylamine. The solution was heated to reflux for 4 d. The reaction mixture was then concentrated and redissolved in 50 mL of xylenes and treated with pyridinium hydrochloride (0.5 g) and the mixture was heated to reflux for 4 d. The reaction mixture was concentrated and taken up in 100 mL of EtOAc and washed with saturated NaHCO3 solution, H2O (2×) and brine. The organic portion was dried over Na2SO4 and concentrated. The resulting syrup was purified by column chromatography (SiO2, 80% EtOAc/hexanes) to give N-{2-[2-(ethoxymethyl)-6,7-dimethyl-4-phenoxy-1H-imidazo[4,5-c]pyridin-1-yl]-1,1-dimethylethyl}acetamide (980 mg) as a mustard colored foam.

Quelle