Benzyl Bromide → HCID 131719463, compound

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Reaction Steps

When the bridging group is carbonyl, the Grignard reagent of 8-bromo-1,4-dioxaspiro[4.5]decane is first prepared. The precursor 8-bromo-1,4-dioxaspiro[4.5]decane is prepared by the method of E. I. Snyder (JOC, 36, 403 (1971)). The Grignard reagent is in turn reacted with an appropriately substituted or unsubstituted benzaldehyde, for example, 3-trifluoromethylbenzaldehyde and then treated with aqueous ammonium chloride, yielding [(1,4-dioxaspiro[4.5]decan-8-yl)(phenyl)]methanol. The so-prepared alcohol is treated with sodium hydride in toluene, and then is reacted with phenylmethyl bromide, yielding phenylmethyl [(1,4-dioxaspiro[4.5]decan-8-yl)(phenyl)]methyl ether. The 1,4-dioxaspiro functional group is then cleaved from the so-prepared molecule with acetic acid and water, as previously described, affording the corresponding phenylmethyl [(cyclohexanon-4-yl)(phenyl)]methyl ether. The ether is then reacted with cyanoguanidine, as previously described, yielding the appropriate 2,4-diamino-6-[(phenylmethoxy)(phenyl)methyl]-5,6,7,8-tetrahydroquinazoline. The tetrahydroquinazoline is then cleaved with hydrogen gas in the presence of 5% palladium on charcoal, yielding the corresponding [(2,4-diamino-5,6,7,8-tetrahydroquinazolin-6-yl)(phenyl)]methanol. Using the method of D. Swern (Tetrahedron, 34, 1651-1660 (1978)), the methanol is oxidized with oxalyl chloride and dimethyl sulfoxide in methylene chloride, yielding the targeted 2,4-diamino-6-phenylcarbonyl-5,6,7,8-tetrahydroquinazoline. Example 9 provides a detailed description of how this reaction is conducted.

Provenance & Evidence