Triethyl Phosphate → 4-(2,5-Dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-3-(ethylsulfonyl)benzonitrile

HRID 517269Notes

Reaction equation

HRID 517269 reaction equation
P(OCC)(OCC)(OCC)=O.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[C:26]1(=[O:33])[CH2:31][CH2:30][CH2:29][C:28](=O)[CH2:27]1.[CH2:34]([S:36]([C:39]1[CH:40]=[C:41]([CH:44]=[CH:45][C:46]=1[CH:47]=O)[C:42]#[N:43])(=[O:38])=[O:37])[CH3:35].[F:49][C:50]([F:62])([F:61])[C:51]1[CH:52]=[C:53]([NH:57][C:58]([NH2:60])=[O:59])[CH:54]=[CH:55][CH:56]=1>COC(C)(C)C>[O:59]=[C:58]1[NH:60][CH:47]([C:46]2[CH:45]=[CH:44][C:41]([C:42]#[N:43])=[CH:40][C:39]=2[S:36]([CH2:34][CH3:35])(=[O:37])=[O:38])[C:27]2[C:26](=[O:33])[CH2:31][CH2:30][CH2:29][C:28]=2[N:57]1[C:53]1[CH:54]=[CH:55][CH:56]=[C:51]([C:50]([F:49])([F:61])[F:62])[CH:52]=1

Participants

7

Reactant 5

HCID 6535Triethyl PhosphateHCID 104341,3-CyclohexanedioneHCID 14812Phosphorus oxide (P4O10)HCID 25712(3-Trifluoromethylphenyl)ureaHCID 581338333-(Ethylsulfonyl)-4-formylbenzonitrile

Product 1

HCID 867323944-(2,5-Dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-3-(ethylsulfonyl)benzonitrile

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of triethyl phosphate (4.6 mL, 26.9 mmol) and phosphorous pentoxide (2.54 g, 17.9 mmol) is heated at 50° C. over night and dilutet with tert-butyl methyl ether (45 mL). Cyclohexane-1,3-dione (3.77 g, 33.6 mmol), 3-(ethylsulfonyl)-4-formylbenzonitrile (5.00 g, 22.4 mmol) and 1-(3-(trifluoromethyl)phenyl)urea (4.57 g, 22.4 mmol) are added, and the mixture is heated at reflux for 4 h. The mixture is cooled at room temperature and concentrated under reduced pressure. The residue is purified by reversed phase HPLC (Agilent ZORBAX™ SB-C18, gradient of acetonitrile in water, 0.15% formic acid). Yield: 930 mg; ESI mass spectrum [M+H]+=504; Retention time HPLC: 1.02 min (Z017_S04).

Workup

  1. temperaturethe mixture is heated
  2. temperatureat reflux for 4 h
  3. temperatureThe mixture is cooled at room temperature
  4. concentrationconcentrated under reduced pressure
  5. customThe residue is purified by reversed phase HPLC (Agilent ZORBAX™ SB-C18, gradient of acetonitrile in water, 0.15% formic acid)
  6. custom1.02 min (Z017_S04)

Sources & evidence

ORD record
ord-b748e31193424503b6b1460c49870459
Source dataset
uspto-grants-2015_08
Patent number
US09115093B2

Reaction notes

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