Sodium Carbonate → 4-(3-Amino-pyrido[2,3-b]pyrazin-6-yl)-2-methoxy-phenol

Temperatur

75 °C

To a suspension of 1.13 g 6-Chloro-pyrido[2,3-b]pyrazin-3-ylamine (5.94 mmol; 1 eq) and 1.67 g 2-Methoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenol (6.55 mmol; 1.1 eq.) in ethylene glycol dimethyl ether (45 mL) under Ar, a solution of 6.29 g sodium carbonate (59.3 mmol; 10 eq.) in water (20 mL) and a suspension of 378 mg FluoroFlash catalyst (0.24 mmol; 0.04 eq.) in undecafluoro(trifluoromethyl)cyclohexane (45 mL) were added. The mixture was heated to 75° C. for 5 hours. Additional 0.76 g (2.97 mmol; 0.5 eq) of 2-Methoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenol were added and the resulting mixture was stirred at 75° C. for 7.5 hours. After cooling to room temperature, the aqueous and organic phase were separated from the fluorous phase and concentrated in vacuo. The residue was dissolved in methanol and methylene dichloride and filtered. The black solution was again concentrated in vacuo. The residue was taken up in water and the resulting solution was neutralized with 1 N HCl whereas the product crystallizes. The brown solid was filtered of, washed with water and dried in vacuo to afford 1.5 g (80.2% yield) of 4-(3-Amino-pyrido[2,3-b]pyrazin-6-yl)-2-methoxy-phenol.

1. additionwere added
2. temperatureAfter cooling to room temperature
3. customthe aqueous and organic phase were separated from the fluorous phase
4. concentrationconcentrated in vacuo
5. dissolutionThe residue was dissolved in methanol
6. filtrationmethylene dichloride and filtered
7. concentrationThe black solution was again concentrated in vacuo
8. customcrystallizes
9. filtrationThe brown solid was filtered of,
10. washwashed with water
11. customdried in vacuo

ORD-Eintrag

ord-b92ca4da2c9f4ce8b2b03dbf65bb7fd1

Quelldatensatz

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08202883B2