Hydrochloric Acid → N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-(2-imidazolyl)carbonyl-6-methylpyrimidinamine

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-(dimethylaminomethyl)imidazole (0.63 g, 5 mmol) in anhydrous diethyl ether (50 mL) at −78° C. under a nitrogen atmosphere was added a solution of n-butyl lithium in hexanes (2.4 M, 2.1 mL, 5 mmol) dropwise and the pale yellow suspension was stirred at −78° C. for 1 h. Methyl 2-(N-(2-bromo-4-(1-methylethyl)-phenyl)-N-ethylamino)-6-methyl-4-pyrimidinecarboxylate (Example 18) (1.47 g, 5 mmol) was added in one portion and the reaction mixture was warmed to room temperature over 23 h. A 1N HCl solution was added until pH=1 (test paper) and the reaction mixture was stirred for 4 h. A 3N NaOH solution was added until the solution became basic (pH=10; test paper). Three extractions with ethyl acetate, drying the combined organic layers over MgSO4, filtration and concentration in vacuo gave a brown oily solid. Column chromatography (chloroform:methanol::9:1) afforded the title product, a yellow glass (900 mg, 42% yield, Rf 0.43): mp 75-76° C.; NMR (CDCl3, 300 MHz): 12.2-12.1 (m, 1H), 7.7 (d, 1H, J=1), 7.45-7.35 (m, 2H), 7.3-7.2 (m, 2H), 6.55 (br s, 1H), 4.3 (sextet, 1H, J=7), 3.8 (sextet, 1H, J=7), 3.05 (septet, 1H, J=7), 2.65 (br s, 3H), 1.4 (d, 6H, J=7), 1.3 (t, 3H, J=7); CI-HRMS: Calcd: 428.1086 (M+H), Found: 428.1089; Anal (C20H24BrN5O) C, 56.08; H, 5.18; N, 16.35; Br, 18.66; Found: C, 56.20; H, 5.10; N, 15.88; Br, 18.73.

Provenance & Evidence