合成路线1

The condensation of protected L-proline (I) with RINK RESIN (II) by means of TBTU, HOBT and DIEA in DMF gives the protected, rein bounded proline (III), which is deprotected by means of piperidine in DMF to yield the resin bounded proline (IV). The condensation of (IV) with 2-bromoacetic acid (V) by means of DIC in the same solvent affords the acyl proline (VI), which is treated with ethylene-1,2-diamine (VII) to provide the aminoacetyl proline (VIII). The condensation of (VIII) with 2-acetyldimedone (IX) gives the regioselectively monoprotected diaminoproline compound (X), which is treated with Boc2O and DIEA in dioxane to protect the secondary amino group of (X) and yield (XI). The selective elimination of the dimedone protecting group with hydrazine in DMF affords compound (XII) selectively monoprotected at the secondary amino group, which is condensed with 6-chloropyridine-3-carbonitrile (XIII) by means of DIEA in NMP to provide the resin adduct (XIV). The cleavage of the resin group of (XIV) by means of TFA and TFAA in dichloromethane takes place with simultaneous dehydration of the carboxamide group and removal of the Boc protecting group affording the trifluoroacetamido derivative (XV). Finally, the trifluoroacetyl group is removed by means of NH3 in aqueous methanol to give rise to the target pyridine carbonitrile derivative.