Bis(2-bromoethyl) ether → 4-(7-bromo-2-methyl-3-(2-methyl-3-(trifluoromethyl)benzyl)-3H-benzo[d]imidazol-5-yl)morpholine

Participants

Reaction Conditions

Reaction Steps

A mixture of 7-bromo-2-methyl-3-(2-methyl-3-(trifluoromethyl)benzyl)-3H-benzo[d]imidazol-5-amine (45 g, 113 mmol), 1-bromo-2-(2-bromoethoxy)ethane (39 g, 169 mmol) and DIPEA (21 g, 169 mmol) in ethylene glycol (700 mL) was stirred at 100° C. for 20 h. It was cooled to rt, and diluted with water (300 mL) and extracted with DCM (300 mL×4). The combined organic layers were washed with brine, dried over sodium sulphate and evaporated. The residue was combined with previous batch prepared similarly and purified by column chromatography (eluted with petroleum ether/ethyl acetate=1/1) to give the product (42 g, 55%) as a yellow solid; LC/MS: MS (ES+) m/e 468 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ ppm 2.36 (s, 3H), 2.53 (s, 3H), 3.06 (t, J=4.5 Hz, 4H), 3.70 (t, J=4.5 Hz, 4H), 5.53 (s, 2H), 6.32 (d, J=7.8 Hz, 1H), 6.99 (d, J=1.5 Hz, 1H), 7.10 (d, J=1.5 Hz, 1H), 7.25 (t, J=7.8 Hz, 1H), 7.61 (d, J=7.8 Hz, 1H).

Provenance & Evidence