The preparation of the intermediate 1,2,3,6-tetrahydropyridine-4-carboxamide (VI) is illustrated in Scheme 1. Demethylation of tetrahydropyridine (I) with ethyl chloroformate in refluxing benzene affords carbamate (II), which is further hydrolyzed to the aminoacid (III) upon heating with concentrated HBr. Subsequent protection of (III) by means of di-t-butyl dicarbonate leads to N-Boc tetrahydropyridine-4-carboxylic acid (IV). Coupling of acid (IV) with ammonia in the presence of EDC/HOBt provides amide (V). The N-Boc protecting group of (V) is then removed with trifluoroacetic acid in CHCl3, yielding tetrahydropyridine (VI)
Condensation of 2,6-dibromo-4-(trifluoromethyl)aniline (VII) with acetoin (VIII), followed by heating the intermediate imine (IX) with malononitrile at 180 C gives rise to the N-aryl pyrrole (X). Acylation of aminopyrrole (X) with Ac2O provides acetamide (XI), which undergoes ring closure to the pyrrolopyrimidine (XII) in hot phosphoric acid. Chlorination of (XII) employing POCl3 furnishes aryl chloride (XIII). This is finally condensed with tetrahydropyridine (VI) to produce the title compound