Pyridine → 3-(2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl)-2-methyl-5-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-6-propylpyrimidin-4(3H)-one

HRID 1718496Notes

Reaction equation

HRID 1718496 reaction equation
[CH3:1][C:2]1[NH:3][C:4](=[O:26])[C:5]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19]([C:24]#[N:25])=[CH:20][CH:21]=[CH:22][CH:23]=3)=[CH:14][CH:13]=2)=[C:6]([CH2:8][CH2:9][CH3:10])[N:7]=1.[CH3:27][C:28]1([CH3:41])[CH2:37][CH2:36][C:35]2[C:30](=[CH:31][CH:32]=[C:33](B(O)O)[CH:34]=2)[O:29]1.[N:42]1C=CC=CC=1.C(N(CC)CC)C.[C:55]([O:58]CC)(=[O:57])C>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.ClCCl>[CH3:27][C:28]1([CH3:41])[CH2:37][CH2:36][C:35]2[C:30](=[CH:31][CH:32]=[C:33]([N:3]3[C:4](=[O:26])[C:5]([CH2:11][C:12]4[CH:17]=[CH:16][C:15]([C:18]5[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=5[C:24]5[NH:42][C:55](=[O:57])[O:58][N:25]=5)=[CH:14][CH:13]=4)=[C:6]([CH2:8][CH2:9][CH3:10])[N:7]=[C:2]3[CH3:1])[CH:34]=2)[O:29]1

Participants

8

Reactant 5

HCID 1049PyridineHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 23005346B-(3,4-Dihydro-2,2-dimethyl-2H-1-benzopyran-6-yl)boronic acidHCID 1354272734'-[(2-Methyl-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile

Product 1

HCID 1359558813-(2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl)-2-methyl-5-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-6-propylpyrimidin-4(3H)-oneYield 80%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 4′-[(2-methyl-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile (0.50 g), (2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl)boronic acid (0.30 g), copper(II) acetate (0.27 g), pyridine (0.59 mL), triethylamine (1.0 mL), molecular sieves 4 A (1.0 g) and dichloromethane (5 mL) was stirred for 3 days. The reaction mixture was diluted with ethyl acetate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography. The resulting crudely purified product was added to a mixture of hydroxylammonium chloride (0.97 g), sodium hydrogen carbonate (1.4 g) and dimethyl sulfoxide (7 mL), and the mixture was stirred at 90° C. for 16 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (7 mL), N,N′-carbonyldiimidazole (0.34 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.31 mL) were added, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous potassium hydrogen sulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound (0.66 g, 80%) as a colorless solid.

Workup

  1. filtrationthe insoluble material was filtered off
  2. concentrationThe filtrate was concentrated under reduced pressure
  3. customthe residue was purified by silica gel column chromatography
  4. additionThe resulting crudely purified product was added to a mixture of hydroxylammonium chloride (0.97 g), sodium hydrogen carbonate (1.4 g) and dimethyl sulfoxide (7 mL)
  5. stirringthe mixture was stirred at 90° C. for 16 hr
  6. additionThe reaction mixture was diluted with ethyl acetate
  7. washwashed with water
  8. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. dissolutionThe residue was dissolved in tetrahydrofuran (7 mL)
  11. additionN,N′-carbonyldiimidazole (0.34 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.31 mL) were added
  12. stirringthe mixture was stirred at room temperature for 1 hr
  13. additionThe reaction mixture was diluted with ethyl acetate
  14. washwashed with saturated aqueous potassium hydrogen sulfate solution
  15. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  16. customThe solvent was evaporated under reduced pressure
  17. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-fd501bd1ee784295a34c4804ef876793
Source dataset
uspto-grants-2010_09
Patent number
US07803940B2

Reaction notes

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