合成路线1

The reaction of 3-formylbenzonitrile (I) with methyl 2-bromoacetate (II) by means of activated Zn in hot THF gives 3-(3-cyanophenyl)-3-hydroxypropionic acid methyl ester (III), which is oxidized with activated MnO2 in hot dichloromethane yielding the oxoester (IV). The bromination of (IV) with NBS in CCl4 affords the alpha bromo derivative (V), which is cyclized with thioacetamide (VI) in hot THF affording 4-(3-cyanophenyl)-2-methylthiazole-5-carboxylic acid methyl ester (VII). The condensation of (VII) with 4'-amino-N-tert-butylbiphenyl-2-sulfonamide (VIII) by means of trimethylaluminum in toluene/dichloromethane gives the corresponding amide (IX), which is treated with hot TFA to eliminate the ter-butyl protecting group yielding intermediate (X). Finally, the cyano group of (X) is treated first with anhydrous HCl in methanol, and finally with ammonium carbonate in the same solvent to obtain the target amidine.