Reaktion #91642

Reaktionsgleichung

Sulfuric acid

Acetonitrile

tert-butyl (4-((2-((6-ethylpyrazin-2-yl)amino)pyridin-4-yl)methoxy)naphthalen-1-yl)carbamate

Intermediate D

tert-butyl (4-((2-((6-ethylpyrazin-2-yl)amino)pyridin-4-yl)methoxy)naphthalen-1-yl)carbamate

ammonia

→

N-(4-(((4-aminonaphthalen-1-yl)oxy)methyl)pyridin-2-yl)-6-ethylpyrazin-2-amine

Ausbeute 75.0%

Lösungsmittel

Water

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe heterogeneous mixture was stirred for an additional 2 h at 20° C
2. 2
   Sonstigewas kept at 20° C.
3. 3
   Temperaturby cooling
4. 4
   workup.STIRRINGAfter stirring for 30 min at 20° C.
5. 5
   Temperaturthe mixture was cooled to 5° C.
6. 6
   workup.STIRRINGstirred for an additional 2 h at 5° C
7. 7
   FiltrationThe precipitate was filtered
8. 8
   Waschenwashed with water (33.4 mL) and 2-propanol (18 mL)
9. 9
   SonstigeThe product was dried at 50° C. in vacuo for 24 h

Vorschrift

Acetonitrile (200 mL) was added to tert-butyl (4-((2-((6-ethylpyrazin-2-yl)amino)pyridin-4-yl)methoxy)naphthalen-1-yl)carbamate (Intermediate D (protected)) (10.5 g) and the heterogeneous mixture was stirred at 20° C. Sulfuric acid (4.5 eq, 5.5 mL) was added over 2 h at 20° C. The heterogeneous mixture was stirred for an additional 2 h at 20° C. Aqueous ammonia (10 eq, 17 mL) was added to the reaction mixture over 15 min and the temperature was kept at 20° C. by cooling. Water (33.4 mL) was added to the heterogeneous mixture over 5 min at 20° C. After stirring for 30 min at 20° C., the mixture was cooled to 5° C. and stirred for an additional 2 h at 5° C. The precipitate was filtered and washed with water (33.4 mL) and 2-propanol (18 mL). The product was dried at 50° C. in vacuo for 24 h to give N-(4-(((4-aminonaphthalen-1-yl)oxy)methyl)pyridin-2-yl)-6-ethylpyrazin-2-amine (6.2 g, 75%).

Quelle