Sodium hydride → {2-[4-(6-Methyl-4-trifluoromethylpyridin-2-yloxy)-phenyl]-ethyl}-thiazolo[5,4-d]pyrimidin-7-ylamine

Participants

Reaction Conditions

Reaction Steps

4-[2-(Thiazolo[5,4-d]pyrimidin-7-ylamino)-ethyl]-phenol (0.1 g, 0.37 mmol) was dissolved with magnetic stirring in DMF (1 mL) in a microwave reactor tube, and then treated with NaH (60% dispersion in oil; 13 mg, 0.55 mmol). After bubbling had subsided, 2-chloro-6-methyl-4-trifluoromethylpyridine (86 mg, 0.44 mmol) was added and the reaction mixture was sealed and placed in a CEM Discover® microwave reactor and irradiated for 30 min, with heating to 150° C. After cooling, the reaction mixture was diluted with H2O (5 mL) and partitioned into Et2O (3×10 mL). The pooled organic fractions were diluted with an equal volume of pentane, washed with H2O, dried (Na2SO4) and filtered through a SiO2/Celite plug. The filtrate was concentrated in vacuo to provide a brown wax (126 mg). Prep RP-HPLC purification (CH3CN/H2O eluent; C18 column) afforded {2-[4-(6-methyl-4-trifluoromethylpyridin-2-yloxy)-phenyl]-ethyl}-thiazolo[5,4-d]pyrimidin-7-ylamine (Compound 62; 36 mg) as an off white powder: mp 111-112° C.; 1H NMR (CDCl3) δ 8.76 (s, 1H), 8.55 (s, 1H), 7.31-7.29 (d, J=8.6 Hz, 2H), 7.11-7.07 (m, 3H), 6.83 (s, 1H), 6.22 (br s, 1H), 3.96-3.95 (br m, 2H), 3.05 (t, J=7.2 Hz, 2H), 2.51 (s, 3H); ESIMS m/z 432.2 ([M+H]+).

Provenance & Evidence