Pyridine → HCID 136146799, compound

HRID 1674000Notes

Reaction equation

HRID 1674000 reaction equation
[CH3:1][C:2]1[NH:3][C:4](=[O:28])[C:5]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[C:21]([C:26]#[N:27])=[CH:22][CH:23]=[CH:24][CH:25]=3)=[CH:16][CH:15]=2)=[C:6]([CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[N:7]=1.[C:29]1(B(O)O)[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C([N:40](CC)CC)C.N1C=CC=CC=1.[C:51]([O:54]CC)(=[O:53])C>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH3:1][C:2]1[N:3]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:4](=[O:28])[C:5]([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]3[NH:40][C:51](=[O:53])[O:54][N:27]=3)=[CH:18][CH:19]=2)=[C:6]([CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[N:7]=1

Participants

8

Reactant 5

HCID 1049PyridineHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 66827Phenylboronic AcidHCID 135430594HCID 135430594, compound

Product 1

HCID 136146799HCID 136146799, compoundYield 49%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 4′-[(2-methyl-6-oxo-4-pentyl-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile (1.0 g), phenylboronic acid (1.00 g), triethylamine (2.0 mL), pyridine (1.0 mL) and molecular sieves 4 A (2.0 g) in methylene chloride (15 mL) was added copper(II) acetate (1.0 g), and the mixture was stirred for 2 days. The reaction mixture was diluted with ethyl acetate. The insoluble material was filtered off through celite, and the filtrate was concentrated. The residue was added to a mixture of hydroxylammonium chloride (1.87 g), sodium hydrogen carbonate (2.71 g) and dimethyl sulfoxide (14 mL) previously stirred at 40° C. for 30 min, and the mixture was stirred at 90° C. for 18 hr. The reaction mixture was allowed to cool to room temperature, ethyl acetate and water were added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated. The residue was dissolved in tetrahydrofuran (15 mL), N,N′-carbonyldiimidazole (0.57 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.52 mL) were added, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was diluted with ethyl acetate, washed with 1 M hydrochloric acid 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 as a colorless solid (0.67 g, 49%).

Workup

  1. filtrationThe insoluble material was filtered off through celite
  2. concentrationthe filtrate was concentrated
  3. additionThe residue was added to a mixture of hydroxylammonium chloride (1.87 g), sodium hydrogen carbonate (2.71 g) and dimethyl sulfoxide (14 mL)
  4. stirringpreviously stirred at 40° C. for 30 min
  5. stirringthe mixture was stirred at 90° C. for 18 hr
  6. additionethyl acetate and water were added
  7. extractionthe mixture was extracted with ethyl acetate
  8. washThe organic layer was washed with saturated brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customthe solvent was evaporated
  11. dissolutionThe residue was dissolved in tetrahydrofuran (15 mL)
  12. additionN,N′-carbonyldiimidazole (0.57 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.52 mL) were added
  13. stirringthe mixture was stirred at room temperature for 3 hr
  14. additionThe reaction mixture was diluted with ethyl acetate
  15. washwashed with 1 M hydrochloric acid
  16. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  17. customThe solvent was evaporated under reduced pressure
  18. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-79d4015895fb43028ba98a615774d67b
Source dataset
uspto-grants-2011_08
Patent number
US07998968B2

Reaction notes

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