Triethylamine → 3-{1-[5-(6-Bromopyridin-2-yl)-thiazol-2-yl]piperidin-4-yl}propionic acid methyl ester

Participants

Reaction Steps

To an solution of 2-bromo-6-chloromethylpyridine (1.88 g, 1.11 mmol) obtained in Step 1 of Example 1 in ethanol (20 ml), 3-(1-thiocarbamoylpiperidin-4-yl)propionic acid methyl ester (2.10 g, 9.12 mmol) obtained in Step 1 was added and the mixture was heated at reflux overnight. The reaction solution was cooled to room temperature, dimethylformamide dimethylacetal (1.8 ml, 14 mmol) and triethylamine (3.8 ml, 27 mmol) were added, and heated at reflux for 1 hour. After the reaction solution was concentrated, water was added, and it was extracted with ethyl acetate and washed with a saturated brine. The organic layer was dried over magnesium sulfate and the residue obtained by vacuum concentration was purified by chromatography on silica gel (n-hexane:ethyl acetate=50:50 to 0:100) and the title compound (748 mg, 20%) was obtained.

Provenance & Evidence