合成路线1

Treatment of 2-fluorobenzyl bromide (I) with hydrazine hydrate in refluxing EtOH gives 2-fluorobenzyl hydrazine (II) (1), which by cyclocondensation with the sodium salt of ethyl cyanopyruvate (III) — prepared by reaction of diethyl oxalate (IV) with acetonitrile mediated by NaOEt (2) — by means of TFA in refluxing dioxane yields the 5-aminopyrazole derivative (V). Condensation of intermediate (V) with 3-dimethylaminoacrolein (VI) in the presence of TFA in refluxing dioxane provides the pyrazolo[3,4-b]pyridine derivative (VII), which is amidated with methanolic ammonia, affording amide (VIII). Treatment of amide (VIII) with pyridine and trifluoroacetic anhydride in THF followed by methanolysis of the resulting nitrile (IX) by means of NaOMe in MeOH generates the methyl imidoate (X), which, without isolation, undergoes amination with NH4Cl in the presence of glacial acetic acid in refluxing MeOH to give the carboxamidine (XI). Coupling of amidine (XI) with phenylazomalononitrile (XII) by means of NaOMe in DMF at 110 °C affords diamine (XIII), which upon reduction with H2 over Raney-Ni in H2O/DMF at 62 °C provides triamine (XIV). Acylation of amine (XIV) with methyl chloroformate (XV) in pyridine affords carbamate (XVI), which is finally N-methylated by means of MeI and NaH in DMF (3) or LiHMDS in THF (4). Scheme 1.