合成路线1

1) The cyclization of 2-acetylglutaric acid diethyl ester (I) with acetamidine (II) by means of sodium ethoxide in refluxing ethyl ether gives the pyrimidinone derivative (III), which by treatment with refluxing phosphorus oxychloride is converted into the chloropyrimidine (IV). The cyclization of (IV) with 4-bromobenzylamine (V) by means of NaHCO3 in refluxing butanol affords 8-(4-bromobenzyl)-2,4-dimethyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-7-one (VI), which is condensed with 2-(2-tert-butyltetrazol-5-yl)phenylboronic acid (VII) by means of tetrakis(triphenylphosphine)palladium in refluxing toluene/ethanol to give 8-[2'-(2-tert-butyltetrazol-5-yl)biphenyl-4-ylmethyl]-2,4-dimethyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-7-one (VIII). Finally, this compound is deprotected with methanesulfonic acid in refluxing toluene. (1,2) 2) The boronic acid (VII) has been obtained as follows: The cyclization of 2-bromobenzonitrile (IX) with sodium azide in hot DMF, followed by protection with tert-butanol in trifluoroacetic acid/H2SO4 gives 5-(2-bromophenyl)-2-tertbutyltetrazole (X), which is finally condensed with triisopropyl borate by means of butyllithium in THF and hydrolyzed with HCl. (1,2)