Bromine → N-[3-(2-bromo-1,3-thiazol-5-yl)-5-methylphenyl]-4-(trifluoromethyl)pyrimidin-2-amine

Participants

Reaction Steps

Lithium diisopropylamide (1.8 M in THF/heptane/ethylbenzene, 11.4 mL, 20.5 mmol) was cooled to −70° C. Intermediate 4 (2.3 g, 6.8 mmol) in THF (23 mL) was added slowly over 15 minutes, keeping the temperature at −65° C. The reaction was allowed to stir for 30 minutes following the addition and then bromine (0.53 mL, 10.3 mmol) was added. The reaction was stirred for 30 minutes and then quenched with 20 mL of water and warmed to rt. The reaction was diluted with EtOAc (50 mL). The layers were separated and the organic portion was washed with Na2SO3 (10% aqueous), brine, dried over MgSO4 and concentrated in vacuo. Purification via column chromatography (ISCO, dry load with silica gel, Hexane-50% EtOAc:Hexane) to provide N-[3-(2-bromo-1,3-thiazol-5-yl)-5-methylphenyl]-4-(trifluoromethyl)pyrimidin-2-amine (1.88 g, 4.53 mmol, 66%). MS APCI: [M+H]+ m/z 414.8, 416.8. 1H NMR (600 MHz, CDCl3) δ 8.64 (d, 4.9, 1H), 7.88 (s, 1H), 7.74 (s, 1H), 7.33 (s, 1H), 7.05 (t, J=6.4, 1H), 7.01 (s, 1H), 2.38 (s, 3H).

Provenance & Evidence