2-Bromothiazole → N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(2-thiazolyl)carbonyl-6-methylpyrimidinamine

Participants

Reaction Conditions

Reaction Steps

To a solution of n-butyl lithium in hexanes (2.4 M, 1.34 mL, 3.24 mmol) in anhydrous THF (5 mL) at −78° C. under a nitrogen atmosphere was added 2-bromothiazole (0.49 g, 0.27 mL, 3.0 mmol) dropwise. After the addition was complete, the reaction mixture was stirred at −78° C. for 30 min. A solution of methyl 2-(N-(2-bromo-4-(1-methylethyl)-phenyl)-N-ethylamino)-6-methyl-4-pyrimidinecarboxylate (Example 18) (1.0 g, 2.5 mmol) in anhydrous THF (10 mL) was added dropwise. The reaction mixture was then warmed to −60° C. and stirred for 4 h. A saturated aqueous solution of NaHCO3 was added and the reaction mixture was warmed to ambient temperature. Three extractions with ethyl acetate, followed by two washings of the combined organic layers with water, drying over MgSO4, filtration and concentration in vacuo gave a dark brown oil. Column chromatography (ethyl acetate: hexanes::1:1) afforded the title product, a brown solid (950 mg, 85% yield, Rf 0.43): mp 97-98.5° C.; NMR (CDCl3, 300 MHz):8.0 (s, 1H), 7.60 (s, 1H), 7.4-7.2 (m, 4H, J=6), 3.05-2.9 (m, 1H), 2.8-2.7 (m, 1H), 2.6 (br s, 3H), 1.4-1.2 (m, 9H); CI-HRMS Calcd: 445.0698 (M+H), Found: 445.0699; Anal.(C20H21BrN4S): C, 54.05; H, 4.73; N, 12.61; Br, 18.02; S, 7.21; Found: C, 53.86; H, 4.66; N, 12.53; Br, 18.20; S, 7.46.

Provenance & Evidence