Diisopropylethylamine → 3-(benzyloxy)-5-bromo-N-(4-(2-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl)thiazol-2-yl)pyridin-2-amine

Participants

Reaction Steps

To a mixture of 3-(2-(3-(benzyloxy)-5-bromopyridin-2-ylamino)thiazol-4-yl)propanoic acid (0.200 g, 0.461 mmol), N,N-diisopropylethylamine (0.0882 ml, 0.507 mmol) in DMF (5 mL) at ambient temperature was added N-((dimethylamino)fluoromethylene)-N-methylmethanaminium hexafluorophosphate(V) (0.122 g, 0.461 mmol). The mixture was stirred for 30 minutes at ambient temperature, and then N-hydroxyacetamidine (0.0375 g, 0.507 mmol) was added in one portion. The reaction mixture was heated at 110° C. overnight and then cooled to ambient temperature. Ethyl acetate was added and the organic layer was washed with water. The combined organic layers were dried over Na2SO4, filtered, and concentrated to a residue that was purified on a silica gel column, eluting with 40% EtOAc/Hexanes. The isolated material was recrystallized from EtOAc/Hexanes and dried under high vacuum to afford 3-(benzyloxy)-5-bromo-N-(4-(2-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl)thiazol-2-yl)pyridin-2-amine (0.110 g, 50% yield) as a tan solid. 1H NMR (DMSO-d6) δ 2.30 (s, 3H), 3.05 (t, J=7.6 Hz, 2H), 3.26 (t, J=7.6 Hz, 2H), 5.29 (s, 2H), 6.73 (s, 1H), 7.35 (t, J=7.2 Hz, 1H), 7.42 (t, J=7.2 Hz, 2H), 7.58 (s, 1H), 7.60 (s, 1H), 7.63 (d, J=1.6 Hz, 1H), 7.97 (d, J=2.0 Hz, 1H), 10.32 (s, 1H); Mass Spectrum (apci) 472 (M+H).

Provenance & Evidence