合成路线1

Nitration of vanillin acetate (I) by means of HNO3 yields the 2-nitrobenzaldehyde derivative (II), which by hydrolysis of the acetate ester with K2CO3 in MeOH provides 2-nitrovanillin (III). Protection of phenol (III) by means of benzyl bromide and K2CO3 in DMF gives the corresponding benzyl ether (IV), which by reaction of the aldehyde moiety with iodine and excess NH3 in H2O/THF results in nitrile (V). Reduction of the nitro group in compound (V) using Fe and AcOH, followed by cyclization of the resulting aminonitrile (VI) with ethylenediamine (VII) in the presence of sulfur affords imidazoline (VIII). Subsequent ring closure of the aminoimidazoline derivative (VIII) with cyanogen bromide (IX) by means of Et3N in CH2Cl2 yields the imidazo[1,2-c] quinazoline derivative (X), which is then debenzylated by means of TFA to give the corresponding phenol (XI). Alkylation of phenol (XI) with 4-(3-chloropropyl)morpholine (XII) in the presence of Cs2CO3 in DMF affords the morpholinopropyl ether (XIII) (1), which is finally condensed with 2-aminopyrimidine-5-carboxylic acid (XIV) using PyBOP and DIEA in DMF .
2-Aminopyrimidine-5-carboxylic acid (XIV) is prepared by cyclization of sodium 2-(dimethoxymethyl)-3-methoxy-3-oxoprop-1(Z)-en-1-olate (XV) with guanidine hydrochloride (XVI) to provide methyl 2-aminopyrimidine-5-carboxylate (XVII), which is then hydrolyzed with LiOH in MeOH .