Reaktion #1122960

Reaktionsgleichung

1-(6-sulphanyl-benzothiazol-2-yl)-3-(2-morpholin-4-yl-ethyl)urea

potassium carbonate

hydrogen carbonate

1,2,4-triazolo[4,3-b]pyridazine

→

1,3-benzothiazol-2-amine

Lösungsmittel

water

dimethyl sulphoxide

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeequipped with a magnetic stirrer
2. 2
   SonstigeThe suspension thus obtained
3. 3
   FiltrationThe solid is filtered off
4. 4
   Waschenwashed with 3×100 cm3 of water
5. 5
   Sonstigespin-filter-dried
6. 6
   SonstigeThe brown powder thus obtained
7. 7
   Sonstigeis purified by chromatography on silica gel (eluent: 95/5/0.5 dichloromethane/methanol/aqueous ammonia)
8. 8
   workup.ADDITIONA small amount of methanol and of hydrochloric acid in solution in dioxane is added to the fractions
9. 9
   workup.ADDITIONcontaining the expected product (to improve solubility)
10. 10
    Einengenconcentrated under reduced pressure
11. 11
    SonstigeThe oil thus obtained
12. 12
    SonstigeThe precipitate formed
13. 13
    Filtrationis filtered off
14. 14
    Waschenwashed with 3×20 cm3 of water
15. 15
    Sonstigedried under vacuum

Vorschrift

280 mg of 1-(6-sulphanyl-benzothiazol-2-yl)-3-(2-morpholin-4-yl-ethyl)urea, 2 cm3 of dimethyl sulphoxide and 240 mg of potassium carbonate are introduced, at 20° C., in a microwave tube equipped with a magnetic stirrer. The suspension thus obtained is stirred for 5 minutes before the addition of 200 mg of 3-chloro-6-(1-methyl-1H)-pyrazol-4-yl)-1,2,4-triazolo[4,3-b]pyridazine. The reaction mixture is then heated in a microwave oven for 10 minutes at 190° C., and then poured into 100 cm3 of water. The resulting mixture is stirred for 30 minutes under cold conditions. The solid is filtered off, washed with 3×100 cm3 of water and then spin-filter-dried. The brown powder thus obtained is purified by chromatography on silica gel (eluent: 95/5/0.5 dichloromethane/methanol/aqueous ammonia). A small amount of methanol and of hydrochloric acid in solution in dioxane is added to the fractions containing the expected product (to improve solubility). The fractions are combined and concentrated under reduced pressure. The oil thus obtained is taken up with 20 cm3 of a saturated aqueous solution of hydrogen carbonate (pH 8-9). The precipitate formed is filtered off and then washed with 3×20 cm3 of water and dried under vacuum. 120 mg of 6-{[6-(1-methyl-1H)-pyrazol-4-yl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulphanyl}-1,3-benzothiazol-2-amine are thus obtained in the form of a light brown solid.

Quelle