Ethyl orthoformate → 5-(4-{[4-(2-Methyl-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl)-6-phenyl-1H-imidazo[4,5-b]pyridine

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Reaction Steps

6-(4-{[4-(2-Methyl-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl)-5-phenylpyridine-2,3-diamine (4-4, 0.055 g, 0.11 mmol) was heated at reflux in triethylorthoformate. After 3 h the reaction was concentrated and stirred in 1M HCl for 1 h. The solution pH was adjusted to 7 with saturated aqueous Na2CO3. The mixture was extracted 3× with DCM. The residue was purified by flash column chromatography (elute with a gradient of 95:5 DCM/MeOH to 90:10). The resulting impure product was dissolved in 2 ml of formic acid and the resulting solution was heated to reflux for 2 h. The reaction was concentrated, diluted with saturated aqueous NaHCO3, and extracted 3× with DCM. The extracts were dried over Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography (elute with a gradient of 95:5 DCM MeOH to 90:10) to afford 5-(4-{[4-(2-Methyl-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl)-6-phenyl-1H-imidazo[4,5-b]pyridine (6-1). 1H NMR (CDCl3) δ 8.20 (s, 1H), 7.93 (s, 1H), 7.42 (d, 2H, J=11.0 Hz), 7.37 (d, 2H, J=10.8 Hz), 7.37-7.21 (m, 6H), 4.20 (m, 1H), 3.65 (s, 2H), 3.14 (m, 2H), 2.65 (s overlapping with m, 5H), 2.23 (m, 2H), 1.80 (m, 2H). MS m/z (M+H)=499.16.

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