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Dimethyl Sulfoxide → 3-{[5-(hydroxymethyl)pyridin-2-yl]methyl}-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 1718820
Notes
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Reaction equation

HRID 1718820 reaction equation
[Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[Si]([O:20][CH2:21][C:22]1[CH:23]=[CH:24][C:25]([CH2:28][N:29]2[C:34](=[O:35])[C:33]([CH2:36][C:37]3[CH:42]=[CH:41][C:40]([C:43]4[C:44]([C:49]#[N:50])=[CH:45][CH:46]=[CH:47][CH:48]=4)=[CH:39][CH:38]=3)=[C:32]([CH2:51][CH2:52][CH3:53])[N:31]=[C:30]2[CH3:54])=[N:26][CH:27]=1)(C(C)(C)C)(C)C>C(OCC)(=O)C>[OH:20][CH2:21][C:22]1[CH:23]=[CH:24][C:25]([CH2:28][N:29]2[C:34](=[O:35])[C:33]([CH2:36][C:37]3[CH:42]=[CH:41][C:40]([C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=4[C:49]4[NH:3][C:4](=[O:7])[O:5][N:50]=4)=[CH:39][CH:38]=3)=[C:32]([CH2:51][CH2:52][CH3:53])[N:31]=[C:30]2[CH3:54])=[N:26][CH:27]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 21645Hydroxylamine HClHCID 516892Sodium BicarbonateHCID 574607604'-[(1-{[5-({[Tert-butyl(dimethyl)silyl]oxy}methyl)pyridin-2-yl]methyl}-2-methyl-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile

Product 1

HCID 136146848
3-{[5-(hydroxymethyl)pyridin-2-yl]methyl}-2-methyl-5-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-6-propylpyrimidin-4(3H)-one
Yield 56%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of hydroxylammonium chloride (0.97 g), sodium hydrogen carbonate (1.56 g) and dimethyl sulfoxide (15 mL) was stirred at 40° C. for 30 min, 4′-[(1-{[5-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyridin-2-yl]methyl}-2-methyl-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile (0.54 g) was added, 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 and the residue was dissolved in tetrahydrofuran (20 mL). N,N′-carbonyldiimidazole (0.18 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.15 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was adjusted to pH 5 with water and 1 M hydrochloric acid, and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (20 mL), tetrabutylammonium fluoride (1.0 M tetrahydrofuran solution, 2.7 mL) was added, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was adjusted to pH 5 with water and 1 M hydrochloric acid, and extracted with ethyl acetate. The ethyl acetate layer was washed 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 colorless crystals (0.27 g, 56%).

Workup

  1. stirringthe mixture was stirred at 90° C. for 16 hr
  2. washwashed with water
  3. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. dissolutionthe residue was dissolved in tetrahydrofuran (20 mL)
  6. additionN,N′-carbonyldiimidazole (0.18 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.15 mL) were added
  7. stirringthe mixture was stirred at room temperature for 2 hr
  8. extractionextracted with ethyl acetate
  9. washThe ethyl acetate layer was washed with saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customThe solvent was evaporated under reduced pressure
  12. dissolutionThe residue was dissolved in tetrahydrofuran (20 mL)
  13. additiontetrabutylammonium fluoride (1.0 M tetrahydrofuran solution, 2.7 mL) was added
  14. stirringthe mixture was stirred at room temperature for 3 hr
  15. extractionextracted with ethyl acetate
  16. washThe ethyl acetate layer was washed with saturated brine
  17. dry with materialdried over anhydrous magnesium sulfate
  18. customThe solvent was evaporated under reduced pressure
  19. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-35f1353fc023478a912eb153b91253d4
Source dataset
uspto-grants-2010_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07803940B2

Reaction notes

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