To a suspension of (R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride (1.0 g, 2.76 mmol) and acetic acid (2.5 mL, 43.4 mmol) in ethanol (7 mL) was added triethylamine (1.5 mL, 10.8 mmol). A solution of ethyl 2-cyclopropylpyrimidine-4-carbimidate (530 mg, 2.77 mmol) in ethanol (3 mL) was added. The reaction mixture was heated at reflux for 30 min, then was cooled. The solvent was removed under reduced pressure and ethyl acetate (100 mL) was added to the residue followed by water (10 mL) and a saturated aqueous solution of ammonium chloride (50 mL). The layers were separated and the organics were washed with a saturated aqueous solution of sodium bicarbonate (75 mL) and brine (50 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure. To the resulting residue was added dichloromethane (4 mL) and methyl tert-butyl ether (35 mL). The mixture was stirred at 40° C. unit it was homogeneous. The solution was cooled to room temperature and stirred for 18 h. The resulting solids were filtered and rinsed with ether to afford the title compound. 1H NMR (400 MHz, CDCl3) δ 1.10-1.17 (m, 2H) 1.18-1.23 (m, 2H), 1.57-1.70 (m, 1H) 1.82-2.05 (m, 7H) 2.27-2.34 (m, 1H) 2.63-2.72 (m, 1H) 2.97-3.07 (m, 1H) 3.14-3.22 (m, 1H) 3.43-3.54 (m, 3H) 3.58-3.67 (m, 1H) 4.37 (d, 1H) 4.53 (d, 1H) 6.76 (d, 1H) 7.95 (m, 2H) 8.67 (d, 1H) 10.46 (br, 1H). MS (ES+) (M+H) 418.5; LCMS retention time 2.72 min (Method L).
