3,5-Dichlorophenol → 2,4-Di[(1,1-dimethylethyl)carbonylamino]-6-phenoxyimino-5,6,7,8-tetrahydroquinazoline

HRID 727151Notes

Reaction equation

HRID 727151 reaction equation
[C:1]1([O:7][NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ClC1C=C(O)C=C(Cl)C=1.[N+](C1C=C([N+]([O-])=O)C=CC=1ON)([O-])=O.ClC1C=C(ON)C=C(Cl)C=1.[CH3:42][C:43]([C:46]([NH:48][C:49]1[N:58]=[C:57]([NH:59][C:60]([C:62]([CH3:65])([CH3:64])[CH3:63])=[O:61])[C:56]2[CH2:55][C:54](=O)[CH2:53][CH2:52][C:51]=2[N:50]=1)=[O:47])([CH3:45])[CH3:44]>C(O)C>[CH3:45][C:43]([C:46]([NH:48][C:49]1[N:58]=[C:57]([NH:59][C:60]([C:62]([CH3:65])([CH3:64])[CH3:63])=[O:61])[C:56]2[CH2:55][C:54](=[N:8][O:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:53][CH2:52][C:51]=2[N:50]=1)=[O:47])([CH3:42])[CH3:44]

Participants

7

Reactant 5

HCID 115713,5-DichlorophenolHCID 87140O-(2,4-dinitrophenyl)hydroxylamineHCID 2794249O-Phenylhydroxylamine2×HCID 11736040O-(3,5-Dichlorophenyl)hydroxylamineHCID 197051902,4-Di[(1,1-dimethylethyl)carbonylamino]-5,6,7,8-tetrahydro-6-quinazolinone

Product 1

HCID 536662182,4-Di[(1,1-dimethylethyl)carbonylamino]-6-phenoxyimino-5,6,7,8-tetrahydroquinazoline

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

When the bridging group n is =NO--, 2,4-diamino-5,6,7,8-tetrahydroquinazoline 6-ethylene ketal is prepared from 1,4-cyclohexanedione mono-ethylene ketal and cyanoguanidine, as previously described. The 2,4-diamino moieties are then protected by the reaction of 2,4-diamino-5,6,7,8-tetrahydroquinazoline 6-ethylene ketal with pivalic anhydride in the presence of 4-dimethylaminopyridine, yielding 2,4-di[(1,1-dimethylethyl)carbonylamino]-5,6,7,8-tetrahydroquinazoline 6-ethylene ketal. The 6-ethylene ketal functional group is then cleaved from the so-prepared molecule with acetic acid and water, affording the corresponding 2,4-di[(1,1-dimethylethyl)carbonylamino]-5,6,7,8-tetrahydro-6-quinazolinone. A second intermediate, an O-(phenyl)hydroxylamine, is prepared by the reaction of an appropriately substituted or unsubstituted phenol, for example, 3,5-dichlorophenol, with O-(2,4-dinitrophenyl)hydroxylamine [prepared by the method of T. Sheradsky et al (Tetrahedron, 28, 3833 (1972)). The so-prepared O-(phenyl)hydroxylamine, for example, O-(3,5-dichlorophenyl)hydroxylamine, is then reacted with the 2,4-di[(1,1-dimethylethyl)carbonylamino]-5,6,7,8-tetrahydro-6-quinazolinone in ethanol, yielding the corresponding 2,4-di[(1,1-dimethylethyl)carbonylamino]-6-phenoxyimino-5,6,7,8-tetrahydroquinazoline. Treatment of the 2,4-di[(1,1-dimethylethyl)carbonylamino]-6-phenoxyimino-5,6,7,8-tetrahydroquinazoline with methanolic hydrochloric acid yields the targeted 2,4-diamino-6-phenoxyimino-5,6,7,8-tetrahydroquinazoline. Example 12 provides a detailed description of how this reaction is conducted.

Workup

  1. customprepared by the method of T

Sources & evidence

ORD record
ord-71cb1ebb8f254d4e86bbf46ebe28733c
Source dataset
uspto-grants-1998_01
Patent number
US05712281

Reaction notes

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