HCID 19705242, compound → HCID 53898675, compound

HRID 1735280Notes

Reaction equation

HRID 1735280 reaction equation
[C:1]1([C:7]#[C:8][CH:9]2[CH2:14][CH2:13][C:12](=O)[CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:16]([NH:18][C:19]([NH2:21])=[NH:20])#[N:17]>>[NH2:21][C:19]1[N:18]=[C:16]([NH2:17])[C:13]2[CH2:14][CH:9]([C:8]#[C:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:10][CH2:11][C:12]=2[N:20]=1

Participants

3

Reactant 2

HCID 19705242HCID 19705242, compoundHCID 178418324HCID 178418324, compound

Product 1

HCID 53898675HCID 53898675, compound

Procedure

When n is the bridging group --C(Cl)=CH--, 1,4-cyclohexanedione mono-ethylene ketal is reduced with sodium borohydride in ethanol, yielding the corresponding 1,4-dioxaspiro[4.5]decan-8-ol. The so-prepared alcohol is then treated with methanesulfonyl chloride under basic conditions in methylene chloride, affording 8-methylsulfonyloxy-1,4-dioxaspiro[4.5]decane, which is in turn treated with sodium hydride in tetrahydrofuran, and then is reacted with trimethylsilylacetylene, yielding 8-(trimethylsilylethynyl)-1,4-dioxaspiro[4.5]decane. This compound is then treated with sodium carbonate in methanol to unprotect the ethynyl moiety, affording 8-ethynyl-1,4-dioxaspiro[4.5]decane. The so-prepared ethynyl compound is reacted with an appropriately substituted or unsubstituted phenyl iodide, for example, 3,5-di(trifluoromethyl)phenyl iodide, under basic conditions in the presence of bis(triphenylphosphine)palladium(II) chloride and copper(I) iodide in acetonitrile, and then is treated with 1N hydrochloric acid, yielding the corresponding 4-(phenylethynyl)cyclohexanone. The cyclohexanone is then reacted with cyanoguanidine, as previously described, affording the 2,4-diamino-6-phenylethynyl-5,6,7,8-tetrahydroquinazoline. Chlorination of the 6-phenylethynyl-5,6,7,8-tetrahydroquinazoline, using the methods of J. Cousseau (JCS Faraday II, 1973, 1821, and JCS Perkin I, 1977, 1797), affords the targeted 2,4-diamino-6-[1-chloro-2-phenylethenyl]-5,6,7,8-tetrahydroquinazoline. Example 8 provides a detailed description of how this reaction is conducted.

Sources & evidence

ORD record
ord-74b26662fc1444b7a5a4b3f4566d2ebc
Source dataset
uspto-grants-1996_07
Patent number
US05536725

Reaction notes

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