Reaction Steps
To a cold (0°), stirred solution of ethyl 2-methyl-8-[(1-phenylcyclopropyl)methoxy]imidazo[1,2-α]pyridine-3-carboxylate (0.629 g, 1.83 mmol, see example 30) in anhydrous tetrahydrofuran (12 mL) under argon was added lithium aluminum hydride (0.104 g, 2.74 mmol). The reaction mixture was stirred for 1 h at 0° C., then quenched with water (25 mL) and extracted successively with ethyl acetate (75 mL) and dichloromethane (3×30 mL). The organic extracts were combined, dried over anhydrous sodium sulfate and concentrated in vacuo to yield 0.485 g (86% yield) of {2-methyl-8-[(1-phenylcyclopropyl)methoxy]imidazo[1,2-α]pyridin-3-yl}methanol free base as a pale yellow solid. A stirred solution of the free amine (0.479 g, 1.55 mmol) in anhydrous methanol (27 mL) was treated with ethereal hydrogen chloride to form the hydrochloride salt. After the solvent was removed in vacuo, the residue was triturated in anhydrous diethyl ether to yield a gummy solid. Recrystallization of this material from a mixture of diethyl ether and methanol yielded 0.509 g (95% yield) of the title compound as an off-white solid. 1H-NMR (300 MHz, CDCl3) δ 14.92 (s, 1H, +NH), 8.41 (s, 1H, Ar), 7.57 (m, 2H, Ar), 7.21 (m, 2H, Ar), 7.10 (m, 1H, Ar), 6.96 (m, 1H, Ar), 6.70 (m, 1H, Ar), 4.86 (s, 2H, HOCH2), 4.21 (s, 2H, CH2O), 2.59 (s, 3H, CH3), 1.06 (m, 4H, CH2CH2); 13C-NMR (75 MHz, CDCl3, APT) δ 144.21 (+), 142.21 (+), 132.30(+), 131.66(+), 129.87(−), 128.32(−), 126.81 (−), 123.23 (+), 119.12(−), 116.61 (−), 109.86 (−), 77.85 (+), 51.30 (+), 25.34 (+), 11.59 (+), 9.90 (−); LRMS-FAB m/z: MH+ 309 (100%); Anal. calcd for C19H20N2O2.HCl: C, 66.18; H, 6.14; N, 8.12%. found: C, 64.67; H, 6.36; N, 7.64%.
