合成路线1

Condensation of 4-hydroxypiperidine (I) with methyl 3,4-difluorobenzoate (II) in DMSO yields derivative (III), which is first mesylated with methanesulfonyl chloride (MsCl) and Et3N in CH2Cl2 and then subjected to reaction with NaN3 in DMF to provide azido derivative (IV). Hydrogenation of (IV) over Pd/C in HOAc/H2O/dioxane affords amino derivative (V), which is then condensed with 2-bromopyrimidine (VI) in DMSO in the presence of DIEA, yielding derivative (VII). Methyl ester group of (VII) is then subjected to saponification by means of aqueous NaOH in THF/MeOH, and the resulting carboxylic acid is coupled to diaminopropionate derivative (VIII) in DMF by means of EDC, HOBt and N-methylmorpholine (NMM) to furnish amide (IX). Hydrolysis of the t-butyl ester group of (IX) by treatment with TFA in CH2Cl2 affords carboxylic acid (X), which is finally hydrogenated over Pd/C in dioxane/H2O to give the target compound.