Methyl 3-mercaptopropionate → Methyl 3-(5-(benzyloxy)-6-(4-methylthiazol-2-ylamino)pyridin-3-ylthio)propanoate

Participants

Reaction Steps

A nitrogen purged 50 mL round-bottomed flask was charged with 3-(benzyloxy)-5-bromo-N-(4-methylthiazol-2-yl)pyridin-2-amine (prepared according to Example 1; 1.50 g, 3.99 mmol), Pd2dba3 (0.091 g, 0.099 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (0.115 g, 0.199 mmol), and dioxane (20 mL). N-ethyl-N-isopropylpropan-2-amine (1.4 ml, 8.0 mmol) and methyl 3-mercaptopropanoate (0.49 mL, 4.4 mmol) were added and the flask was plunged into a 100° C. oil bath for 2 hours. The reaction mixture was cooled to room temperature and solvent removed. The residue was purified on silica gel (20 to 30% ethyl acetate/hexanes) to afford methyl 3-(5-(benzyloxy)-6-(4-methylthiazol-2-ylamino)pyridin-3-ylthio)propanoate (1.30 g, 78.5% yield) as a white solid. 1H NMR (CDCl3) δ 8.57 (bs, 1H), 8.04 (d, 1H), 7.41 (m, 5H), 7.22 (d, 1H), 6.42 (s, 1H), 5.12 (s, 2H), 3.68 (s, 3H), 3.03 (t, 2H), 2.56 (t, 2H), 2.32 (s, 3H); Mass spectrum (apci) m/z=325.0 (100) 416.0 (50).

Provenance & Evidence