Water → HCID 67278809, compound

HRID 1696251Notes

Reaction equation

HRID 1696251 reaction equation
[H-].[Na+].C([O:5][C:6](=[O:16])[CH2:7]P(OCC)(OCC)=O)C.[O:17]=[C:18]1[N:29]([C@H:30]2[CH2:35][CH2:34][CH2:33][C@H:32]([CH:36]=O)[CH2:31]2)[C:21]2=[C:22]3[CH:28]=[CH:27][NH:26][C:23]3=[N:24][CH:25]=[C:20]2[NH:19]1.O>O1CCCC1>[O:17]=[C:18]1[N:29]([C@H:30]2[CH2:35][CH2:34][CH2:33][C@H:32](/[CH:36]=[CH:7]/[C:6]([OH:5])=[O:16])[CH2:31]2)[C:21]2=[C:22]3[CH:28]=[CH:27][NH:26][C:23]3=[N:24][CH:25]=[C:20]2[NH:19]1

Participants

6

Reactant 4

HCID 962WaterHCID 13345Triethyl phosphonoacetateHCID 24758Sodium hydrideHCID 86635096HCID 86635096, compound

Product 1

HCID 67278809HCID 67278809, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of sodium hydride (60% in oil) (7 mg) in tetrahydrofuran (1 ml) was added dropwise ethyl(diethoxyphosphoryl)acetate (53 μl). After stirring at ambient temperature for 5 minutes, trans-3-(2-oxo-3,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-1(2H)-yl)cyclohexanecarbaldehyde (50 mg) was added and stirred at ambient temperature for overnight. The reaction mixture was poured into water, and extracted with EtOAc and tetrahydrofuran. The organic layer was washed with brine, dried over MgSO4 and evaporated in vacuo. The residue was purified by preparative thin layer chromatography eluting with dichloromethane:methanol=10:1. The fractions containing desired compound were combined and evaporated. The residue was dissolved in dioxane (250 μl), and 1M NaOH solution (176 μl) was added, then stirred at 110° C. for 2 hours. After cooling to the ambient temperature, 1M HCl (176 μl) and pH 4 buffer (5 ml) was added to the reaction mixture. Resulting precipitates were collected by filtration and washed with water to give (2E)-3-[trans-3-(2-oxo-3,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-1(2H)-yl)cyclohexyl]acrylic acid (11.0 mg) as a brown powder.

Workup

  1. stirringstirred at ambient temperature for overnight
  2. extractionextracted with EtOAc and tetrahydrofuran
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated in vacuo
  6. customThe residue was purified by preparative thin layer chromatography
  7. washeluting with dichloromethane
  8. additionThe fractions containing desired compound
  9. customevaporated
  10. dissolutionThe residue was dissolved in dioxane (250 μl)
  11. addition1M NaOH solution (176 μl) was added
  12. stirringstirred at 110° C. for 2 hours
  13. temperatureAfter cooling to the ambient temperature, 1M HCl (176 μl) and pH 4 buffer (5 ml)
  14. additionwas added to the reaction mixture
  15. customResulting
  16. customprecipitates
  17. filtrationwere collected by filtration
  18. washwashed with water

Sources & evidence

ORD record
ord-21e6886d78ff4c119375c60818466772
Source dataset
uspto-grants-2012_04
Patent number
US08163767B2

Reaction notes

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