N-Trityl Losartan Carboxaldehyde synthesis

Yield:133910-00-6 88%

Reaction Conditions:

with trimethylamine in dichloromethane at 20; for 5 h;

Steps:

3.9 6.1.3.9 2-Butyl-5-chloro-3-[2'-(2-trityl-2H-tetrazol-5-yl)biphenyl-4-ylmethyl]-3H-imidazole-4-carbaldehyde (9) [42]

To a solution of 8 (1.02g, 2.43mmol) in anhydrous CH₂Cl₂ (10mL) were added trimethylamine (373μL, 2.68mmol) and trityle chloride (747mg, 2.68mmol). The mixture was stirred at room temperature for 5h. EtOAc (60mL) was added and the resulting solution was washed with water (4×30mL), dried (MgSO₄) and the solvent was removed under vacuum to give a residue which was purified by column chromatography (eluent: cyclohexane/EtOAc, 85:15) to give 1.41g (2.13mmol, 88% yield) of white solid. M. p. 86-89°C. ¹H NMR (250MHz, DMSO-d₆): δ 0.81 (t, J=7.3Hz, 3H, CH₃), 1.18-1.33 (m, 2H, CH₂), 1.43-1.57 (m, 2H, CH₂), 2.60-2.66 (m, 2H, CH₂), 5.58 (s, 2H, CH₂N), 7.01-7.09 (m, 4H, H_arom), 7.50-7.70 (m, 4H, H_arom), 9.68 (s, 1H, CHO).

References:

Meyer, Maxime;Foulquier, Sébastien;Dupuis, Fran?ois;Flament, Stéphane;Grimaud, Linda;Henrion, Daniel;Lartaud, Isabelle;Monard, Gérald;Grillier-Vuissoz, Isabelle;Boisbrun, Michel [European Journal of Medicinal Chemistry,2018,vol. 158,p. 334 - 352]