The nitration of 1,2,3-trichlorobenzene (I) with concentrated HNO3 gives 2,3,4-trichloronitrobenzene (II), which by reaction with cuprous cyanide in hot pyridine is converted to 2,3-dichloro-6-nitrobenzonitrile (III). The reduction of (III) with borane in THF yields 2,3-dichloro-6-nitrobenzylamine (IV), which by reaction with ethyl bromoacetate (V) by means of triethylamine in refluxing dioxane affords ethyl N-(2,3-dichloro-6-nitrobenzyl)glycinate (VI). The reduction of (VI) with SnCl2 in concentrated HCl gives ethyl N-(6-amino-2,3-dichlorobenzyl)glycinate (VII), which is cyclized with cyanogen bromide (VIII) in toluene affording ethyl 5,6-dichloro-3,4-dihydro-2-(1H)-iminoquinazoline-3-acetate (IX). Finally, this compound is submitted to a new cyclization by means of triethylamine in refluxing ethanol.
The reaction of 3-chloroaniline (X) with choral hydrate (XI) and hydroxylamine gives isonitroso-3-chloroacetanilide (XII), which is cyclized by means of H2SO4 to 4-chloroisatin (XIII). Chlorination of (XIII) with SO2Cl2 affords 4,5-dichloroisatin (XIV), which is oxidized with H2O2 yielding 5,6-dichloroanthranilic acid (XV). The reduction of (XV) with borane in THF gives 6-amino-2,3-dichlorobenzyl alcohol (XVI), which by reaction with SOCl2 in benzene is converted to 6-amino-2,3-dichlorobenzyl chloride (XVII). This compound is condensed with ethyl glycinate (XVIII) by means of triethylamine in refluxing methylene chloride to give ethyl N-(6-amino-2,3-dichlorobenzyl)glycinate (VII), which is cyclized with cyanogen bromide (VIII) in toluene affording ethyl 5,6-dichloro-3,4-dihydro-2-(1H)-iminoquinazoline-3-acetate (IX). Finally, this compound is submitted to a new cyclization by means of triethylamine in refluxing ethanol.
The nitration of 2,3-dichlorobenzaldehyde (I) with HNO3/H2SO4 gives 2,3-dichloro-6-nitrobenzaldehyde (II), which is reduced with NaBH4 in methanol, yielding 2,3-dichloro-6-nitrobenzyl alcohol (III). The reaction of (III) with SOCl2 and TEA affords the benzyl chloride (IV), which is condensed with glycine ethyl ester (V) by means of TEA to provide the adduct (VI). The reduction of the nitro group of (VI) with SnCl2 in aq. HCl or H2 over PtO2/C in ethanol gives the expected amino derivative (VII), which is cyclized with CN-Br in toluene to yield the iminoquinazoline (VIII). Finally, this compound is further cyclized by means of TEA in water to afford the target imidazoquinazolinone.
The condensation of 2-nitro-6-chlorobenzyl chloride (I) with ethyl glycinate (II) by means of triethylamine in refluxing ethanol gives ethyl N-(2-nitro-6-chlorobenzyl)glycinate (III), which is reduced with H2 over Pd/C in ethanol yielding ethyl N-(2-amino-6-chlorobenzyl)glycinate (IV). The cyclization of (IV) with cyanogen bromide (A) in refluxing ethanol affords 6-chloro-1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2-one (V), which is finally chlorinated with Cl2 and FeCl3 in hot nitromethane.