1,3-Dioxolane-4-methanamine, 2,2-dimethyl- → rac-2-(4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)-N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)ethanamine

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-(4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)ethyl methanesulfonate (195 mg, 0.389 mmol) and rac-2,2-dimethyl-1,3-dioxolane-4-methanamine (51 mg, 0.389 mmol) in acetonitrile (6 mL) is stirred at 65° C. for 16 h. The mixture is separated by prep. HPLC to give rac-2-(4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)-N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)ethanamine (180 mg) as a white solid. This material is dissolved in 2 N aq. HCl (1 mL) and dioxane (5 mL) and stirred at 60° C. for 1 h. The solvent is evaporated and the crude product is purified by prep. TLC eluting with DCM containing 15% of methanol followed by prep. HPLC to give the title compound (16 mg) as a white solid; LC-MS: tR=0.91 min, [M+H]+=497.11; 1H NMR (CD3OD): δ 7.82 (s, 1H), 7.80 (s, 1H), 7.48 (s, 1H), 7.22 (s, 1H), 4.00 (t, J=5.0 Hz, 2H), 3.98 (s, 3H), 3.82-3.89 (m, 1H), 3.53-3.63 (m, 2H), 3.20-3.30 (m, 1H), 3.08 (t, J=5.0 Hz, 2H), 2.88 (dd, J1=12.1 Hz, J2=3.7 Hz, 1H), 2.70-2.81 (m, 3H), 2.38 (s, 3H), 2.05-2.15 (m, 2H), 1.84-1.95 (m, 4H), 1.69-1.81 (m, 2H), 1.30 (t, J=7.5 Hz, 3H).

Provenance & Evidence