Benzyl Bromide → HCID 131719463, compound

HRID 1735282Notes

Reaction equation

HRID 1735282 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[CH2:17][OH:18])[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[H-].[Na+].[C:21]1([CH2:27]Br)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C1(C)C=CC=CC=1>[O:1]1[C:5]2([CH2:6][CH2:7][CH:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[CH2:17][O:18][CH2:27][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:9][CH2:10]2)[O:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 19705209HCID 19705209, compound

Product 1

HCID 131719463HCID 131719463, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

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.

Sources & evidence

ORD record
ord-d0b492a12d414ab2baad8b73fc37ac8a
Source dataset
uspto-grants-1996_07
Patent number
US05536725

Reaction notes

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