1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Tert-butyl (6-(5-(3-fluoro-2-((1-(2-hydroxyethyl)-4-phenylpiperidin-4-yl)methylcarbamoyl)pyridin-4-ylthio)thiazol-2-ylamino)pyridin-3-yl)methyl(methyl)carbamate

Participants

Reaction Steps

4-(2-(5-((Tert-butoxycarbonyl(methyl)amino)methyl)pyridin-2-ylamino)thiazol-5-ylthio)-3-fluoropicolinic acid (0.120 g, 0.244 mmol) was diluted in NMP (4 mL) and treated with HOBT (0.043 g, 0.317 mmol), EDAC (0.094 g, 0.488 mmol) and 2-(4-(aminomethyl)-4-phenylpiperidin-1-yl)ethanol (0.074 g, 0.317 mmol) and diisopropylethylamine (0.213 mL, 1.22 mmol) at 23° C. The reaction was stirred overnight then water was added and this was extracted with ethyl acetate/THF (3×). The organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated to give a residue which was purified on preparative HPLC (acetonitrile/water/TFA). The title material was obtained (0.140 g, ˜81%) as a solid which was used as such for the next step. LC/MS (M+H)+: 708. Ret. time: 1.612 min. (Condition F).

Provenance & Evidence