Methyl 3-mercaptopropionate → (S)-methyl 3-(6-(3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-ylamino)-5-(2-methylpyridin-3-yloxy)pyridin-3-ylthio)propanoate

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-N-(5-bromo-3-(2-methylpyridin-3-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decane-2-yl)-1,2,4-thiadiazol-5-amine (3.1 g, 6.14 mmol) in dioxanes (30 mL) continuously purged with nitrogen was added Xanphos (0.177 g, 0.303 mmol), Pd2dba3 (0.14 g, 0.153 mmol), methyl 3-mercaptopropanoate (0.73 g, 6.14 mmol) and N,N-diisopropylethylamine (1.17 mL, 6.45 mmol) and the reaction was heated overnight at 80° C. The reaction was concentrated in vacuo and the residue purified over silica gel (5% MeOH/CH2Cl2) to afford (S)-methyl 3-(6-(3-(1,4-dioxaspiro[4.5]decan-2-yl)-1,2,4-thiadiazol-5-ylamino)-5-(2-methylpyridin-3-yloxy)pyridin-3-ylthio)propanoate (2.3 g, 68%).

Provenance & Evidence