By reaction of 4-(p-fluorobenzoyl)piperidine (I) with 3-(2-chloroethyl)-2,4-(1H,3H)-quinazolinedione (II) by means of Na2CO3 in refluxing 4-methyl-2-pentanone. The starting compounds are prepared as follows: 1) The Grignard reaction of N-benzyl-4-cyanopiperidine (III) with p-fluorophenylmagnesium bromide (IV) ethyl ether gives N-benzyl-4-p-fluorobenzoyl)piperidine (V), which by reaction with Na2CO3 and ethyl chloroformate (A) is converted into N-ethoxycarbonyl-4-(p-fluorobenzoyl)piperidine (VI). Finally, this compound is hydrolyzed with 48% HBr to give (I). 2) The reaction of ethyl anthranilate (VII) with ethyl chloroformate (A) in refluxing xylene gives ethyl 2-(ethoxycarbonylamino)benzoate (VIII), which is cyclized with 2-aminoethanol (B) at 170 C to afford 3-(2-hydroxyethyl)-2,4-(1H,3H)-quinazolinedione (IX). Finally, this compound is treated with SOCl2 in refluxing chloroform to afford (II).
By condensation of 2,3-dihydro-5H-oxazole[2,3-b]quinazolin-5-one (I) with 4-(4-fluorobenzoyl)piperidine (II) in refuxing toluene.
The condensation of N-(2-bromoethyl)-2-nitrobenzamide (I) with 4-(4-fluorobenzoyl)piperidine (II) by means of Na2CO3 in refluxing methyl isobutyl ketone gives N-[2-[4-(4-fluorobenzoyl)-2-piperidinyl]ethyl]-2-nitrobenzamide (III), which is reduced with H2 over Pt/C in methanol yielding the corresponding amino derivative (IV). Finally, this compound is cyclized with urea (V) in refluxing xylene.