Sodium Hydroxide → 6-((4-((((trans)-2-Phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)nicotinic acid

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To a solution 2,2,2-trifluoro-N-(trans-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide (130 mg, 0.398 mmol) in 1,2-dichloroethane (DCE) (2 mL) were added methyl 6-formylnicotinate (86 mg, 0.518 mmol) and sodium triacetoxyborohydride (127 mg, 0.598 mmol), and the reaction mixture was stirred at room temperature for 18 h. The mixture was quenched with water (2 mL) and extracted with DCM (3×). The extract was dried (Na2SO4) and concentrated to give a crude product. The product was dissolved in methanol (2.000 mL) and sodium hydroxide (3M, 0.664 mL, 1.992 mmol) was added. The mixture was stirred at room temperature for 3 h and concentrated. The residue was treated with methanol and filtered. The filtrate was purified using reverse-phase HPLC under the acidic conditions to give 110 mg of product as pale yellow solid (HCl salt). MS: (M+H)+=366.4. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.24 (m, 1H),1.54-1.73 (m, 3H), 1.98-2.12 (m, 3H), 2.59-2.72 (m, 1H), 2.94 (m, 4H), 3.45 (br. s., 2H), 4.54 (br. s., 2H), 7.16-7.25 (m, 3H), 7.27-7.35 (m, 2H), 7.81 (d, J=8.08 Hz, 1H), 8.38 (dd, J=8.08, 2.27 Hz, 1H), 9.12 (d, J=1.52 Hz, 1H), 9.78 (br. s., 2H), 10.72 (br. s., 1H).

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