2,6-Lutidine → HCID 136146825, compound

HRID 1719078Notes

Reaction equation

HRID 1719078 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-9fbeade576064a9598cc484d7d3044e8
Source dataset
uspto-grants-2010_09
Patent number
US07803940B2

Reaction notes

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