Hydrochloric Acid → N-cyclopropyl-3-{[4-({5-[2-(dimethylamino)ethoxy]pyridin-2-yl}methoxy)benzoyl]amino}-4-methylbenzamide

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Reaction Steps

To a stirred solution of N-cyclopropyl-3-[(4-{[5-(1,3-dioxolan-2-ylmethoxy)pyridin-2-yl]methoxy}benzoyl)amino]-4-methylbenzamide (1.0 g, 2 mmol) in methanol (20 mL) was added hydrochloric acid (36% aqueous solution, 10 mL). After 2 hours the solution was basified by addition of 2N sodium hydroxide (55 mL). The precipitate was filtered off and dissolved in THF (100 mL), then stirred while adding a solution of dimethylamine (2M in THF, 2 mL, 4 mmol), titanium isopropoxide (3 mL, 10 mmol) and sodium triacetoxyborohydride (2.2 g, 10 mmol). After 16 hours the mixture was basified with 2N sodium hydroxide, stirred for 10 minutes and the top layer decanted. The lower layer was stirred with THF (50 mL) and decanted again, the combined top layers were dried over magnesium sulphate. The title compound was isolated by chromatography on silica, eluting with a gradient of 0-30% methanol in ethyl acetate to give a gum (120 mg); NMR Spectrum: (CDCl3) 0.60 (m, 2H), 0.83 (m, 2H), 2.32 (s, 3H), 2.40 (s, 6H), 2.82 (t, 2H), 2.90 (m, 1H), 4.17 (t, 2H), 5.20 (s, 2H), 6.60 (s, 1H), 7.06 (d, 2H), 7.26 (dd, 2H), 7.42 (d, 1H), 7.56 (d, 1H), 7.86 (d, 2H), 7.90 (s, 1H), 8.10 (s, 1H), 8.32 (s, 1H); Mass Spectrum: M+H+ 489.

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