2,6-Lutidine → HCID 136146825, compound

HRID 1674409Notes

Reaction equation

HRID 1674409 reaction equation
[CH2:1]([C:3]1[N:4]=[C:5]([CH2:38][CH2:39][CH3:40])[N:6]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]3[C:31]([C:36]#[N:37])=[CH:32][CH:33]=[CH:34][CH:35]=3)=[CH:26][CH:25]=2)[C:7](=[O:22])[C:8]=1[C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[O:15][C:14]([CH3:20])([CH3:19])[CH2:13][CH:12]2[OH:21])[CH3:2].[N:41]1C(C)=CC=CC=1C.FC(F)(F)S(O[Si](C(C)C)(C(C)C)C(C)C)(=O)=O.[C:67]([O:70]CC)(=[O:69])C>ClCCl>[CH2:1]([C:3]1[N:4]=[C:5]([CH2:38][CH2:39][CH3:40])[N:6]([CH2:23][C:24]2[CH:25]=[CH:26][C:27]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[C:36]3[NH:41][C:67](=[O:69])[O:70][N:37]=3)=[CH:28][CH:29]=2)[C:7](=[O:22])[C:8]=1[C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[O:15][C:14]([CH3:20])([CH3:19])[CH2:13][CH:12]2[OH:21])[CH3:2]

Participants

6

Reactant 4

HCID 79372,6-LutidineHCID 8857Ethyl AcetateHCID 2724529Triisopropylsilyl trifluoromethanesulfonateHCID 594694034'-{[4-ethyl-5-(4-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl)-6-oxo-2-propylpyrimidin-1(6H)-yl]methyl}biphenyl-2-carbonitrile

Product 1

HCID 136146825HCID 136146825, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 4′-{[4-ethyl-5-(4-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl)-6-oxo-2-propylpyrimidin-1(6H)-yl]methyl}biphenyl-2-carbonitrile (1.5 g) and 2,6-lutidine (0.98 mL) in dichloromethane (10 mL) was added triisopropylsilyl trifluoromethanesulfonate (1.5 mL) at 0° C. After stirring for 2 hr, the reaction mixture was diluted with ethyl acetate, washed with water, dried over sodium sulfate and concentrated. The residue was dissolved in dimethyl sulfoxide (5 mL), and then hydroxylamine hydrochloride (1.7 g) and sodium hydrogen carbonate (2.5 g) were added. The mixture was stirred overnight at 90° C. After cooling, the reaction mixture was diluted with ethyl acetate, washed with water, dried over sodium sulfate and concentrated. The residue was dissolved in tetrahydrofuran (5 mL), and N,N′-carbonyldiimidazole (0.6 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.6 mL) were added. After stirring for 30 min, the reaction mixture was diluted with ethyl acetate, washed with 1 M hydrochloric acid, dried over sodium sulfate and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a colorless solid (1.3 g, 77%).

Workup

  1. washwashed with water
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in dimethyl sulfoxide (5 mL)
  5. additionhydroxylamine hydrochloride (1.7 g) and sodium hydrogen carbonate (2.5 g) were added
  6. stirringThe mixture was stirred overnight at 90° C
  7. temperatureAfter cooling
  8. additionthe reaction mixture was diluted with ethyl acetate
  9. washwashed with water
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated
  12. dissolutionThe residue was dissolved in tetrahydrofuran (5 mL)
  13. additionN,N′-carbonyldiimidazole (0.6 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.6 mL) were added
  14. stirringAfter stirring for 30 min
  15. additionthe reaction mixture was diluted with ethyl acetate
  16. washwashed with 1 M hydrochloric acid
  17. dry with materialdried over sodium sulfate
  18. concentrationconcentrated
  19. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-01265b1a141d4e568f961a2326d2e875
Source dataset
uspto-grants-2011_08
Patent number
US07998968B2

Reaction notes

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