Triphenylphosphine → HCID 59570930, compound

HRID 2192939Notes

Reaction equation

HRID 2192939 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[CH:28]1([C:31]2[CH:32]=[C:33](/[C:43](=[CH:47]\[C@H:48]3[CH2:68][CH2:67][C:50]4(O[C@H](C5C=CC=CC=5)[C@@H](C5C=CC=CC=5)[O:51]4)[CH2:49]3)/[C:44](O)=[O:45])[CH:34]=[CH:35][C:36]=2[S:37]([CH:40]2[CH2:42][CH2:41]2)(=[O:39])=[O:38])[CH2:30][CH2:29]1.[NH2:69][C:70]1[S:71][C:72]2[C:77]([N:78]=1)=[CH:76][CH:75]=[C:74]([O:79][CH2:80][C:81]([O:83]CC)=O)[N:73]=2.C(=O)(O)[O-].[Na+]>ClCCl.N1C=CC=CC=1>[CH:28]1([C:31]2[CH:32]=[C:33](/[C:43](=[CH:47]\[C@H:48]3[CH2:68][CH2:67][C:50](=[O:51])[CH2:49]3)/[C:44]([NH:69][C:70]3[S:71][C:72]4[C:77]([N:78]=3)=[CH:76][CH:75]=[C:74]([O:79][CH2:80][CH2:81][OH:83])[N:73]=4)=[O:45])[CH:34]=[CH:35][C:36]=2[S:37]([CH:40]2[CH2:42][CH2:41]2)(=[O:39])=[O:38])[CH2:29][CH2:30]1

Participants

8

Reactant 5

HCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 516892Sodium BicarbonateHCID 57630515HCID 57630515, compoundHCID 59571019HCID 59571019, compound

Product 1

HCID 59570930HCID 59570930, compoundYield 14.9%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent4×

Conditions

Temperature
5 °C

Procedure

To a solution of triphenylphosphine (600 mg) in dichloromethane (10 mL) was added N-bromosuccinimide (400 mg) under ice-cooling (at an internal temperature of 5° C. or lower), followed by stirring for 15 minutes, and then a solution of (2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(2R,3R,7S)-2,3-diphenyl-1,4-dioxaspiro[4.4]non-7-yl]acrylic acid (600 mg) in dichloromethane (10 mL) was added thereto under ice-cooling, followed by stirring at room temperature for 20 minutes. To the reaction mixture were added a mixture of ethyl 2-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]acetate (270 mg) in dichloromethane (10 mL) and pyridine (0.17 mL), followed by stirring at room temperature overnight. A saturated sodium bicarbonate solution and dichloromethane were added thereto, and the organic layer was sequentially washed with 1 M hydrochloric acid and saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue thus obtained was purified by silica gel column chromatography (hexane/ethyl acetate). To the obtained colorless amorphous in THF (3 mL)-methanol (3 mL) mixed solution was added 1 M aqueous sodium hydroxide solution (0.6 mL), followed by stirring at room temperature for 30 minutes. The solvent was evaporated under reduced pressure, followed by addition of 1 M hydrochloric acid and ethyl acetate, and the organic layer was sequentially washed with saturated aqueous sodium bicarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue thus obtained was purified by silica gel column chromatography (hexane/ethyl acetate). To a solution of the obtained colorless amorphous in dioxane (5 mL) was added 4 M hydrochloric acid (2 mL), followed by stirring at 50° C. for 3 hours and leaving it to be cooled at room temperature. The solvent was evaporated under reduced pressure, followed by addition of water and ethyl acetate and the organic layer was sequentially washed with saturated aqueous sodium bicarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue thus obtained was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain (2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-[5-(2-hydroxyethoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]-3-[(1S)-3-oxocyclopentyl]acrylamide (89 mg) as a colorless amorphous substance.

Workup

  1. temperatureunder ice-cooling
  2. stirringby stirring at room temperature for 20 minutes
  3. additionTo the reaction mixture were added
  4. stirringby stirring at room temperature overnight
  5. washthe organic layer was sequentially washed with 1 M hydrochloric acid and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customthe residue thus obtained
  9. customwas purified by silica gel column chromatography (hexane/ethyl acetate)
  10. additionTo the obtained colorless amorphous in THF (3 mL)-methanol (3 mL) mixed solution
  11. additionwas added 1 M aqueous sodium hydroxide solution (0.6 mL)
  12. stirringby stirring at room temperature for 30 minutes
  13. customThe solvent was evaporated under reduced pressure
  14. additionfollowed by addition of 1 M hydrochloric acid and ethyl acetate
  15. washthe organic layer was sequentially washed with saturated aqueous sodium bicarbonate and saturated brine
  16. dry with materialdried over anhydrous magnesium sulfate
  17. customThe solvent was evaporated under reduced pressure
  18. customthe residue thus obtained
  19. customwas purified by silica gel column chromatography (hexane/ethyl acetate)
  20. additionTo a solution of the obtained colorless amorphous in dioxane (5 mL) was added 4 M hydrochloric acid (2 mL)
  21. stirringby stirring at 50° C. for 3 hours
  22. customleaving it
  23. temperatureto be cooled at room temperature
  24. customThe solvent was evaporated under reduced pressure
  25. additionfollowed by addition of water and ethyl acetate
  26. washthe organic layer was sequentially washed with saturated aqueous sodium bicarbonate and saturated brine
  27. dry with materialdried over anhydrous magnesium sulfate
  28. customThe solvent was evaporated under reduced pressure
  29. customthe residue thus obtained
  30. customwas purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-13293b44202041848312b6de4a41b244
Source dataset
uspto-grants-2012_12
Patent number
US08329707B2

Reaction notes

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