Acetic acid (2.9 mL, 48.58 mmol) and ethyl 2-(4-chloro-1H-pyrazol-1-yl)-2-methylpropanimidate (Intermediate 54) were added to a solution of (R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone in ethanol, prepared in the previous step. The reaction mixture was heated at reflux for 18 h. The mixture was concentrated and the residue was partitioned between ethyl acetate and water. The organic layer was dried over sodium sulfate, filtered and concentrated. The crude material was purified via column chromatography (100-200 mesh silica gel, 5% methanol in ethyl acetate) to afford the title compound (530 mg, 25% yield over 2 steps). 1H NMR (500 MHz, CDCl3) δ 1.53-1.65 (m, 1H) 1.74-2.00 (m, 7H) 2.10 (s, 6H) 2.58-2.70 (m, 1H) 2.88-2.93 (m, 1H) 3.01-3.09 (m, 1H) 3.40-3.50 (m, 3H) 3.55-3.63 (m, 1H) 4.22 (d, 1H) 4.43 (d, 1H) 6.63 (d, 1H) 7.57 (d, 2H) 7.79 (d, 1H) 10.08 (br s, 1H). MS (ES+APCI) (M+H) 442.2; LCMS retention time 2.216 min (Method N1).
