Pyridine → 2-(2,6-dimethylphenyl)-6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-4-methoxy-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-(2-(2,6-dimethylphenyl)-4-methoxy-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methylpentane-1,3-dione (5.92 g, 15.52 mmol) in THF (80 mL) was added pyridine (5 mL). the resulting solution was evenly divided into four microwave 20 mL vials. To each microwave via was added, methyl hydrazine (0.312 mL, 5.81 mmol) and 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide (Lawesson's reagent) (1.88 g, 4.66 mmol). The vials were immediately capped and heated to 125° C. for 10 min via microwave irradiation. The reaction vials were cooled to r.t. and the reaction mixtures were combined and diluted with brine. The mixture was extracted with DCM three times. The combined organic layers were dried over Na2SO4. After filtration and concentration, the resulting residue was purified via silica gel FCC ((1% MeOH in EtOAc):n-heptane=0 to 100%) to provide 2-(2,6-dimethylphenyl)-6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-4-methoxy-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine. 1H NMR (400 MHz, CD2Cl2) δ ppm 7.15-7.24 (m, 1 H), 7.05-7.12 (m, 2 H), 5.77 (s, 1 H), 4.00-4.04 (m, 2 H), 3.98 (s, 3 H), 3.70 (s, 3 H), 3.28 (t, J=5.8 Hz, 2 H), 3.05 (t, J=5.8 Hz, 2 H), 2.87 (dt, J=13.9, 6.9 Hz, 1 H), 2.12 (s, 6 H), 1.23 (d, J=7.1 Hz, 6 H). MS (ESI+) m/z 392.4 (M+H)+.

Provenance & Evidence