【药物名称】
化学结构式(Chemical Structure):
参考文献No.735366
标题:Novel dihydrofolate reductase inhibitors. Structure-based versus diversity-based library design and high-throughput synthesis and screening
作者:Wyss, P.C.; Gerber, P.; Hartman, P.G.; Hubschwerlen, C.; Locher, H.; Marty, H.-P.; Stahl, M.
来源:J Med Chem 2003,46(12),2304
合成路线图解说明:

Condensation of guanidine nitrate (I) with (ethoxymethylene)malononitrile (II) in the presence of NaOEt yields 2,4-diaminopyrimidine-5-carbonitrile (III). Reduction of nitrile (III) by means of Raney nickel in formic acid leads to aldehyde (IV), which is further reduced to alcohol (V) by means of NaBH4. Treatment of alcohol (V) with HBr in AcOH gives the bromide (VI), which is condensed with pyridine in DMF to form the crystalline pyridinium salt (VII). Finally, displacement of compound (VII) with the tetrahydroisoquinoline (VIII), followed by resolution by chiral HPLC, furnishes the title compound.

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