Potassium Carbonate → Thiazolo[5,4-d]pyrimidin-7-yl-{2-[4-(4-trifluoromethylpyridin-3-yloxy)-phenyl]-ethyl}-amine

Participants

Reaction Steps

2-[4-(4-Trifluoromethylpyridin-3-yloxy)-phenyl]-ethylamine (0.25 g, 0.88 mmol), 7-chlorothiazolo[5,4-d]pyrimidine (0.15 g, 0.88 mmol) and K2CO3 (3 g) were dissolved with magnetic stirring in DMSO (7 mL) in a 25 mL round bottom flask equipped with a dry nitrogen line at 25° C. After placing the flask in a sonication bath for 3 min, the reaction mixture was heated on a steam bath for 2 min. The mixture was filtered, and the filter cake was washed with acetone. The combined filtrates were diluted with 0.15 N HCl (100 mL) and washed successively with Et2O (2×50 mL) and EtOAc (2×50 mL). The pooled organic fractions were filtered and concentrated in vacuo to provide 0.27 g of a yellow gum. The gum was dissolved in a small volume of EtOAc and passed through a short SiO2 column with 1% MeOH/EtOAc as eluent. The appropriate fractions were pooled and concentrated in vacuo to provide a clear colorless oil (0.17 g). Trituration in Et2O followed by decanting of the solvent afforded thiazolo[5,4-d]pyrimidin-7-yl-{2-[4-(4-trifluoromethylpyridin-3-yloxy)-phenyl]-ethyl}-amine (Compound 43; 170 mg) as a yellow solid: mp 83-87° C.; 1H NMR (400 MHz, CDCl3) δ 8.77 (s, 1H), 8.55 (s, 1H), 8.50 (s, 1H), 8.34 (s, 1H), 7.54 (s, 1H), 7.30 (d, J=8.6 Hz, 2H), 7.06-6.99 (m, 2H), 6.22 (s, 1H), 3.94 (dd, J=12.9, 6.5 Hz, 2H), 3.04 (t, J=7.1 Hz, 2H); ESIMS m/z 418.2 ([M+H]+).

Provenance & Evidence