4-Fluorobenzylamine → 2-PYRIMIDINECARBOXAMIDE

Participants

Reaction Steps

To a solution of seven-membered ring-pyrimidine mesylate 2 (6 g) in EtOH (80 mL) was added 4-fluorobenzylamine (5.060 g). The resulting solution was reflux for 8 h. (100% conversion by HPLC). The reaction mixture was concentrated to about 20 mL total volume, and 80 mL of EtOAc was added. To the resulting solution was added 20% brine (15 mL), 4 N HCl (15 mL), and water 10 mL). After a phase cut, the aqueous layer was back-extracted with EtOAc (25 mL). The combined organic layers were washed with 4 N HCl: 20% brine (1:1, 3×15 mL), brine (15 mL). The organic solution was concentrated to a total volume about 30 mL. Hexane (70 mL) was slowly added to the solution over 1 h. The resulting slurry was aged at 0-5° C. for 1 h. The crystalline solid was filtered off, washed with hexane:EtOAc (4:1, 50 mL), dried under vacuum with nitrogen sweep to afford seven-membered ring-pyrimidine amide 10 (5.30 g, 86%, HPLC>97A %). 1H NMR (CDCl3, 400 MHz) δ: 11.85 (br s, 1H), 7.84 (br s, 0.5H), 7.68 (br s, 0.5H), 7.31 (m, 2H), 7.04 (m, 2H), 5.40-4.90 (m, 2H), 4.53 (m, 2H), 3.38 (m, 1H), 2.87 (s, 3H), 2.20-2.15 (m, 3H), 1.90-1.40 (m, 3H), 1.37 (s, 9H).

Provenance & Evidence