Reaktion #168964

Reaktionsgleichung

aniline hydrochloride

guanidine carbonate

(2-isopropyl-4-methoxy-5-nitro-phenoxy)-acetonitrile

Brederick's reagent

aniline hydrochloride

→

5-(2-isopropyl-4-methoxy-5-nitro-phenoxy)-pyrimidine-2,4-diamine

Ausbeute 71.8%

Lösungsmittel

NMP

EtOH

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeAfter 45 min the mixture was evaporated under reduced pressure (50° C., 50 mtorr)
2. 2
   Sonstigeto give an orange solid
3. 3
   TemperaturThe mixture was warmed to reflux
4. 4
   Temperaturat reflux for 4 h
5. 5
   EinengenThe solution was concentrated in vacuo
6. 6
   workup.ADDITIONpoured into H2O
7. 7
   ExtraktionThe mixture was extracted with ethyl acetate
8. 8
   Waschenwashed with H2O
9. 9
   Waschenwashed with brine
10. 10
    Trocknendried over Na2SO4
11. 11
    Einengenconcentrated in vacuo
12. 12
    Sonstigeto afford a yellow-green solid
13. 13
    Temperaturwarmed to 130° C
14. 14
    TemperaturAfter 5 hours the mixture was cooled
15. 15
    FiltrationThe resulting precipitate was filtered
16. 16
    Waschenwashed with H2O
17. 17
    Sonstigedried under vacuum (50° C.)
18. 18
    SonstigeThe crude solid was recrystallized from EtOH

Vorschrift

A mixture of (2-isopropyl-4-methoxy-5-nitro-phenoxy)-acetonitrile (8.785 g, 35.5 mmol) and Brederick's reagent (14.6 mL, 70.9 mmol) was warmed to 100° C. After 45 min the mixture was evaporated under reduced pressure (50° C., 50 mtorr) to give an orange solid. The solid was added to a solution of aniline hydrochloride (9.19 g, 70.9 mmol) in 150 mL of EtOH. The mixture was warmed to reflux. After 16 hr additional aniline hydrochloride (4.596 g, 35.5 mmol) was added mixture was continued at reflux for 4 h. The solution was concentrated in vacuo and poured into H2O. The mixture was extracted with ethyl acetate, washed with H2O, washed with brine, dried over Na2SO4, and concentrated in vacuo to afford a yellow-green solid. This crude product was added to a mixture of 200 mL NMP and guanidine carbonate (17.70 g, 98 mmol) and warmed to 130° C. After 5 hours the mixture was cooled then poured onto 2 l of an ice/H2O mixture. The resulting precipitate was filtered, washed with H2O and dried under vacuum (50° C.). The crude solid was recrystallized from EtOH to afford 5-(2-isopropyl-4-methoxy-5-nitro-phenoxy)-pyrimidine-2,4-diamine (8.14 g, 63%, 3 steps) as a yellow crystalline solid (solvated 1:1 with EtOH). (M+H)+=320.

Quelle