4-N-ethylpyridine-3,4-diamine → Ethyl-2-(2-pyrimidin-2-yl-imidazol-1-ylmethyl)-1H-imidazo[4,5-c]pyridine

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Reaction Steps

To a solution of N4-ethyl-pyridine-3,4-diamine (Justus Liebigs Ann. Chem. (1935) 518, 274, 287) (125 mg, 0.9 mmol) in dichloroethane (10 mL) is added a solution of AlMe3 in toluene (2M, 1.37 mL) dropwise under nitrogen. After addition, the mixture is stirred at room temperature for one hour and (2-pyrimidin-2-yl-imidazol-1-yl)-acetic acid methyl ester (100 mg, 0.45 mmol) is added in one portion. The reaction mixture is heated with stirring at 80° C. for 2 days. After cooled, the mixture is quenched with 5 mL of water, 2 drops of 5 N NaOH and extracted with CH2Cl2 (10 mL×5). The combined organic extracts are dried over Na2SO4, and concentrated. The residue is dissolved in 10 mL of acetic acid and the resulting mixture is heated at 100° C. overnight. After removal of acetic acid under vacuum, the residue is basified with saturated NaHCO3 solution and extracted with CH2Cl2 (10 mL×5). The combined organic extracts are dried over Na2SO4, and concentrated. The residue is purified on a silica gel column with 10:1 CH2Cl2/MeOH as eluent to yield the title compound (40 mg). 1H NMR (CDCl3) δ: 9.09 (s, 1H), 8.85 (d, 2H), 8.46 (d, 1H), 7.26-7.30 (m, 3H), 7.16 (1H), 6.39 (s, 2H), 4.25 (q, 2H), 1.15 (t, 3H).

Provenance & Evidence