4-Piperidinemethanol → (3-(4-((4-(Hydroxymethyl)piperidin-1-yl)methyl)phenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone

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Reaction Steps

Piperidin-4-ylmethanol (0.04 g, 0.35 mmol) was dissolved in dichloromethane (2 mL) and TEA (0.052 ml, 0.38 mmol) was added. Intermediate 55A (0.11 g, 0.29 mmol) was added followed by addition of sodium triacetoxyhydroborate (0.123 g, 0.58 mmol). The mixture was stirred at RT overnight. Dichloromethane (10 mL) and NaHCO3 (sat. 2 mL) were added and the mixture was filtered through a phase separator and the solvent was removed by evaporation. The product was purified by preparative reverse-phase HPLC at pH 10 to give 81 mg (58%). 1H NMR (600 MHz, DMSO) δ 1.05-1.17 (m, 2H), 1.28-1.39 (m, 1H), 1.57-1.66 (m, 2H), 1.82-1.92 (m, 2H), 2.75-2.84 (m, 2H), 3.19-3.27 (m, 3H), 3.83-3.92 (m, 3H), 4.06-4.13 (m, 1H), 4.37-4.45 (m, 1H), 4.5-4.67 (m, 2H), 5.04-5.19 (m, 2H), 6.85 (d, 2H), 7.16-7.27 (m, 4H), 8-8.05 (m, 2H), MS (APCI+) m/z 479 [M+H]+, LC-purity: 99%.

Provenance & Evidence