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0 °C

N4-(2-Fluoro-2-methylpropyl)[1,5]naphthyridine-3,4-diamine (2.12 g, 9.06 mmol) was dissolved in 90 mL of anhydrous CH2Cl2 and the stirred solution was cooled to 0° C. under N2. Triethylamine (1.39 mL, 10.0 mmol) and acetoxyacetyl chloride (1.07 mL, 10.0 mmol) were then added and the reaction mixture was stirred overnight. The reaction mixture was concentrated under reduced pressure and the resulting material was dissolved in 90 mL of ethanol and treated with 5 mL of triethylamine. The mixture was heated at reflux for 4 days. The reaction mixture was then cooled and concentrated under reduced pressure to give a purple solid. The purple solid was partitioned between CH2Cl2 (75 mL) and H2O (75 mL). The layers were separated and the aqueous portion was extracted with CH2Cl2 (2×20 mL). The combined organic portions were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to give a purple solid. The resulting material was dissolved in 50 mL of methanol and treated with 1 mL of saturated aqueous K2CO3 solution. After 1 hour, the mixture was treated with 3.5% NaH2PO4 solution and the methanol was removed by evaporation under reduced pressure. A brown solid precipitated out of the aqueous solution and was isolated by filtration. The brown solid was rinsed with H2O and then dried to give 1.81 g of [1-(2-fluoro-2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-2-yl]methanol.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. dissolutionthe resulting material was dissolved in 90 mL of ethanol
3. additiontreated with 5 mL of triethylamine
4. temperatureThe mixture was heated
5. temperatureat reflux for 4 days
6. temperatureThe reaction mixture was then cooled
7. concentrationconcentrated under reduced pressure
8. customto give a purple solid
9. customThe purple solid was partitioned between CH2Cl2 (75 mL) and H2O (75 mL)
10. customThe layers were separated
11. extractionthe aqueous portion was extracted with CH2Cl2 (2×20 mL)
12. washThe combined organic portions were washed with brine
13. dry with materialdried over Na2SO4
14. filtrationfiltered
15. concentrationconcentrated under reduced pressure
16. customto give a purple solid
17. waitAfter 1 hour
18. customthe methanol was removed by evaporation under reduced pressure
19. customA brown solid precipitated out of the aqueous solution
20. customwas isolated by filtration
21. washThe brown solid was rinsed with H2O
22. customdried