Triethyl Phosphate → Allyl 4-[4-cyano-2-(phenylsulfonyl)phenyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate

HRID 2064401Notes

Reaction equation

HRID 2064401 reaction equation
P(OCC)(OCC)(OCC)=O.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[CH:26]([C:28]1[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][C:29]=1[S:36]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)(=[O:38])=[O:37])=O.[F:45][C:46]([F:58])([F:57])[C:47]1[CH:48]=[C:49]([NH:53][C:54]([NH2:56])=[O:55])[CH:50]=[CH:51][CH:52]=1.[C:59]([O:65][CH2:66][CH:67]=[CH2:68])(=[O:64])[CH2:60][C:61]([CH3:63])=O>CC(OC)(C)C>[C:32]([C:31]1[CH:34]=[CH:35][C:28]([CH:26]2[C:60]([C:59]([O:65][CH2:66][CH:67]=[CH2:68])=[O:64])=[C:61]([CH3:63])[N:53]([C:49]3[CH:50]=[CH:51][CH:52]=[C:47]([C:46]([F:57])([F:58])[F:45])[CH:48]=3)[C:54](=[O:55])[NH:56]2)=[C:29]([S:36]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)(=[O:38])=[O:37])[CH:30]=1)#[N:33]

Participants

7

Reactant 5

HCID 6535Triethyl PhosphateHCID 14812Phosphorus oxide (P4O10)HCID 25712(3-Trifluoromethylphenyl)ureaHCID 70701Allyl acetoacetateHCID 581337454-Formyl-3-(phenylsulfonyl)benzonitrile

Product 1

HCID 44132736Allyl 4-[4-cyano-2-(phenylsulfonyl)phenyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
90 °C

Procedure

The reaction was carried out under argon. Triethyl phosphate (172 mg, 0.947 mmol) and diphosphorus pentoxide (90 mg) were stirred at 40° C. overnight. The mixture was then diluted with MTBE (9.5 ml), and 4-formyl-3-(phenylsulfonyl)benzonitrile (214 mg, 0.789 mmol), 1-[3-(trifluoromethyl)phenyl]urea (0.161 g, 0.789 mmol) and allyl acetoacetate (0.168 g, 1.18 mmol; 1.5 eq.) were added. The mixture was stirred under reflux for 16 h. The reaction mixture was then concentrated by distillative removal of MTBE and subsequently heated at 90° C. for a further 2 h. For work-up, residual solvent was removed under reduced pressure and the residue was taken up in ethyl acetate (150 ml). The organic phase was washed with saturated sodium chloride solution (2×30 ml), dried over solid sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by preparative HPLC (column: Gromsil C-18; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10). The title compound was obtained as a solid (230 mg, 33% of theory).

Workup

  1. additionwere added
  2. temperatureunder reflux for 16 h
  3. concentrationThe reaction mixture was then concentrated by distillative removal of MTBE
  4. customFor work-up, residual solvent was removed under reduced pressure
  5. washThe organic phase was washed with saturated sodium chloride solution (2×30 ml)
  6. dry with materialdried over solid sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by preparative HPLC (column: Gromsil C-18; mobile phase: acetonitrile/water+0.1% TFA 10:90→90:10)

Sources & evidence

ORD record
ord-d48027dcbb8440638caa3140baf42868
Source dataset
uspto-grants-2012_10
Patent number
US08288402B2

Reaction notes

Loading…