Pyridine → 3-Benzyl-6-(methoxycarbonyl)-2-thioxo-1,2,3,4-tetrahydroquinazolin-4-one

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Reaction Steps

This process is illustrated in Scheme 2 below: Methyl 4-aminoisophthalate (2a) is treated with benzyl isothiocyanate, in a solvent such as pyridine or acetic acid, to give 3-benzyl-6-(methoxycarbonyl)-2-thioxo-1,2,3,4-tetrahydroquinazolin-4-one (2b). This compound is heated, in a refluxing alcohol, in the presence of hydrazine hydrate to give the corresponding hydrazine which is in turn cyclized by reaction with a carboxylic acid derivative R1COOH (such as an acid chloride or an orthoester). The 4-benzyl-7-(methoxycarbonyl)-4,5-dihydrotriazolo[4,3-a]quinazolin-5-one (2d) obtained is N4-debenzylated using aluminium chloride in benzene, and the intermediate secondary lactam is then substituted with a halide, in the presence of a base such as cesium carbonate, in a solvent such as dimethylformamide. The N-substituted analogue obtained (2f) is then hydrolysed, preferably in acidic medium, to give the corresponding acid (2g) which may be subsequently subjected to a coupling reaction of peptide type.

Provenance & Evidence