Toluene → 4-(benzyloxy)-N-(4-methylthiazol-2-yl)pyridin-2-amine

Temperature

90 °C

A 250 mL round-bottomed flask was charged with 2-amino-4-methylthiazole (43.8 mL, 17.5 mmol), 4-(benzyloxy)-2-chloropyridine (4.23 g, 19.3 mmol), potassium phosphate (4.09 g, 19.3 mmol), and toluene (44 mL), and the reaction mixture was degassed with nitrogen. Tris(dibenzylideneacetone)-dipalladium (0) (0.401 g, 0.438 mmol) and 9,9-dimethyl-4,5-bis(diphenyl-phosphino)-xanthene (0.279 g, 0.482 mmol) were added, and the reaction mixture was degassed with nitrogen. The reaction mixture was warmed to 90° C., degassed water (15 mL) was added, and reaction mixture was stirred at 90° C. overnight. Water was added, and the reaction mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and filtered through a small plug of silica gel, and the filtrate was concentrated down to 50 mL of ethyl acetate and filtered to afford 4-(benzyloxy)-N-(4-methylthiazol-2-yl)pyridin-2-amine (2.50 g, 47.5% yield) as a white solid. 1H NMR (CDCl3) δ 9.29 (bs, 1H), 8.15 (d, 1H), 7.39 (m, 4H), 7.35 (m, 1H), 6.53 (dd, 1H), 6.41 (d, 1H), 6.36 (d, 1H), 5.07 (s, 2H), 2.33 (s, 3H). Mass spectrum (esi) m/z=298 (M

1. customthe reaction mixture was degassed with nitrogen
2. customthe reaction mixture was degassed with nitrogen
3. customdegassed water (15 mL)
4. additionwas added
5. customreaction mixture
6. extractionthe reaction mixture was extracted with ethyl acetate
7. dry with materialThe organic layer was dried over magnesium sulfate
8. filtrationfiltered through a small plug of silica gel
9. concentrationthe filtrate was concentrated down to 50 mL of ethyl acetate
10. filtrationfiltered

ORD record

ord-9e1bc0a8e00348de9b492dea08001071

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08022222B2