Reaction Steps
A mixture of 1,4-benzodioxan-6-amine (Sigma-Aldrich, 65.8 mg, 0.435 mmol) and (S)-1-(2-chloropyrimidin-4-yl)-N-(4-methylbenzylipiperidine-3-carboxamide (M5, 100 mg, 0.290 mmol) in DMSO (0.6 mL) was heated at 90° C. for 16 hours. The mixture was then cooled to room temperature, filtered and was purified with reversed-phase HPLC (Phenomenex Gemini-NX 10 μL 110 Å, AXIA packed column, 100×50 mm, 60 mL/min, 10-95% ACN/H2O, 0.1% TFA, 10 min gradient). After concentration of the fractions by vacuum distillation, the product was diluted with saturated aqueous NaHCO3 and extracted with DCM (3×). The combined organic layers were dried over Na2SO4, filtered and concentrated to provide the desired product in 18% yield. 1H NMR (300 MHz, CDCl3) δ ppm 1.66-1.79 (m, 2H), 1.85-2.00 (m, 1H), 2.04-2.19 (m, 1H), 2.30 (s, 3H), 2.45 (br. s., 1H), 3.24 (t, J=9.9 Hz, 1H), 3.69 (dd, J=13.7, 8.0 Hz, 1H), 3.83 (d, J=12.6 Hz, 1H), 4.12 (d, J=12.1 Hz, 1H), 4.19 (s, 4H), 4.34 (d, J=5.4 Hz, 2H), 6.00 (d, J=6.1 Hz, 1H), 6.39 (br. s., 1H), 6.76 (d, J=8.6 Hz, 1H), 6.85 (dd, J=10.7, 9.1 Hz, 1H), 6.79-6.92 (m, 1H), 7.07 (s, 4H), 7.17-7.22 (m, 1H), 7.89 (d, J=6.3 Hz, 1H); M+H 460.23367.
