Process for preparation of amidine derivatives

本发明公开了一种由以下反应方案表示的用于制备脒衍生物的方法，其特征在于步骤1和3的反应在乙腈中进行，而步骤2的反应在丙酮中进行： Preparation of an amidine compound (II) comprises: (i) halogenating an aminoketone compound (V) in acetonitrile and hydrolyzing to give a halogenated aminopyridine compound (IV); (ii) reacting (IV) with a ketone (VI) in acetone in the presence of an organic base to give an amide (III); and (iii) reacting (III) with a halogenating agent in acetonitrile in the presence of an organic base and aminating the product. Preparation of an amidine compound of formula (II) comprises: (i) halogenating an aminoketone compound of formula (V) in acetonitrile in the presence of dimethylformamide and hydrolyzing to give a halogenated aminopyridine compound of formula (IV); (ii) reacting (IV) with a ketone of formula RCOR11 (VI) in acetone in the presence of an organic base and optionally a halogenating agent to give an amide of formula (III), and (iii) reacting (III) with a halogenating agent in acetonitrile in the presence of an organic base and then aminating the product. [Image] A : 5-9 membered aliphatic ring containing at least one O, S, SO, SO2 and/or NR1 and optionally substituted by alkyl; R1H, alkyl optionally esterified carboxy, carbamoyl or acyl; R : aryl or heteroaryl (both optionally substituted); R10aryl, heteroaryl, alkyl or cycloalkyl (all optionally substituted), and R11OH or halo. Independent claims are also included for steps (i), (ii) and (iii) per se.