To a solution of 2-(2,6-dimethylphenyl)-6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-ol (2.38 g, 6.3 mmol) in DCM (50 mL) at 0° C., was added (1-chloro-ethylidene)-dimethylammonium chloride (Vilsmeier reagent) (2.421 g, 18.91 mmol). The reaction was stirred at 0° C. for 5 min, then at r.t. for 30 min. Saturated aqueous NaHCO3 was added to quench the reaction. The mixture was extracted with DCM three times. The combined organic layers was dried over Na2SO4. After filtration and concentration, the resulting residue was purified via silica gel FCC (0-100% EtOAc/heptane) to give 4-chloro-2-(2,6-dimethylphenyl)-6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine. 1H NMR (400 MHz, CD2Cl2) δ ppm 7.19-7.27 (m, 1 H), 7.11 (d, J=7.6 Hz, 2 H), 5.80 (s, 1 H), 4.16 (s, 2 H), 3.72 (s, 3 H), 3.32 (t, J=5.9 Hz, 2 H), 3.16 (t, J=5.8 Hz, 2 H), 2.88 (dt, J=13.9, 6.9 Hz, 1 H), 2.11 (s, 6 H), 1.23 (d, J=6.8 Hz, 6 H). MS (ESI+) m/z 396.3 (M+H)+.
