Reaktion #168997

Reaktionsgleichung

Guanidine carbonate

(2-Isopropyl-4-methoxy-5-thiazol-4-yl-phenoxy)-acetonitrile

Brederick's reagent

aniline HCl

→

5-(2-Isopropyl-4-methoxy-5-thiazol-4-yl-phenoxy)-pyrimidine-2,4-diamine

Ausbeute 68.0%

Lösungsmittel

water

NMP

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeExcess Brederick's reagent was removed under reduced pressure
2. 2
   workup.DISSOLUTIONThe residue was dissolved in anhydrous EtOH (10 ml)
3. 3
   TemperaturThe reaction mixture was heated at 80° C. for 18 hrs
4. 4
   Sonstigepartitioned between EtOAc and water
5. 5
   TrocknenThe combined organic extracts were dried over Na2SO4
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated
8. 8
   Temperaturheated to 120° C. for 10 hrs
9. 9
   Extraktionextracted into EtOAc
10. 10
    TrocknenThe combined organic extracts were dried over Na2SO4
11. 11
    Filtrationfiltered
12. 12
    Einengenconcentrated

Vorschrift

A mixture of (2-Isopropyl-4-methoxy-5-thiazol-4-yl-phenoxy)-acetonitrile (0.27 g, 0.94 mmol) and Brederick's reagent (0.35 g, 2.01 mmol) was heated at 100° C. for 2 hrs. Excess Brederick's reagent was removed under reduced pressure. The residue was dissolved in anhydrous EtOH (10 ml) and aniline HCl (0.38 g, 2.93 mmol) was added. The reaction mixture was heated at 80° C. for 18 hrs and partitioned between EtOAc and water. The combined organic extracts were dried over Na2SO4, filtered and concentrated. Guanidine carbonate (0.27 g, 1.49 mmol) and NMP (10 ml) were added and heated to 120° C. for 10 hrs. The reaction mixture was poured into water and extracted into EtOAc. The combined organic extracts were dried over Na2SO4, filtered and concentrated. Flash chromatography on silica (3% MeOH in methylene chloride with 0.1% NH4OH) gave 5-(2-Isopropyl-4-methoxy-5-thiazol-4-yl-phenoxy)-pyrimidine-2,4-diamine (0.15 g, 68%) as a solid. (M+H)=358.

Quelle