[Synthesis]
Step 6) A mixture of 2,4-dimethyl-5,6,8-trihydro-8-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-7H-pyrido[2,3-d]pyrimidin-7-one and 2,4-dimethyl-5,6,8-trihydro-8-[[2'-(1-tert-butyl-1H-tetrazol-5-yl)[1,1'-biphenyl]-4 -yl]methyl]-7H-pyrido[2,3-d]pyrimidin-7-one mixture (200 mg, 0.428 mmol) was dissolved in toluene (4 mL), methanesulfonic acid (280 mL, 4.28 mmol) was added, and heated to reflux for 18 hours. Upon completion of the reaction, the mixture was concentrated and adjusted to pH 8 by the addition of water (2 mL) and 1N KOH solution (4.5 mL).The mixture was extracted with ethyl acetate (EtOAc) to remove unreacted feedstock, followed by acidification of the aqueous phase to pH 5 with 1N HCl to give a gelatinous precipitate. The precipitate was dissolved in ethyl acetate and the solution was dried over anhydrous magnesium sulfate (MgSO4) and concentrated to give a colorless oil. Grinding with a solvent mixture of acetone/ether gave 70 mg (40% yield) of the target product as a white solid with a melting point of 197°C-198°C.1H NMR (DMSO-d6) δ: 2.35 (s, 3H), 2.42 (s, 3H), 2.72 (t, J = 7.2 Hz, 2H), 2.87 (t, J = 7.2 Hz, 2H), 2.17 (s, 2H), 2.17 (s, 2H). 5.17 (s, 2H), 6.99 (d, J = 8.2 Hz, 2H), 7.18 (d, J = 8.2 Hz, 2H), 7.54 (m, 2H), 7.65 (m, 2H). ir (KBr, cm-1): 1710 (C=O). |