Triphenylphosphine → HCID 76609486, compound

HRID 599423Notes

Reaction equation

HRID 599423 reaction equation
[CH:1](=[N:3][O:4][CH2:5][C:6]1[N:7]([CH2:20][CH2:21][CH2:22][CH2:23][NH:24][C:25](=[O:32])[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:8]2[C:13]([CH3:14])=[C:12]([CH3:15])[N:11]3N=N[N:18]=[C:10]3[C:9]=2[N:19]=1)[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClC1C=CC=CC=1Cl>[NH2:18][C:10]1[C:9]2[N:19]=[C:6]([CH2:5][O:4][N:3]=[CH:1][CH3:2])[N:7]([CH2:20][CH2:21][CH2:22][CH2:23][NH:24][C:25](=[O:32])[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:8]=2[C:13]([CH3:14])=[C:12]([CH3:15])[N:11]=1

Participants

4

Reactant 2

HCID 11776TriphenylphosphineHCID 86627657HCID 86627657, compound

Product 1

HCID 76609486HCID 76609486, compoundYield 1.7%

Reagents, catalysts & solvents 1

HCID 72391,2-DichlorobenzeneSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of N-{4-[8-({[ethylideneamino]oxy}methyl)-5,6-dimethyl-7H-imidazo[4,5-c]tetraazolo[1,5-a]pyridin-7-yl]butyl}benzamide (2.0 g, 4.6 mmol), triphenylphosphine (2.4 g, 9.2 mmol), and 1,2-dichlorobenzene (50 mL) was heated at 125° C. for 2 days. The reaction mixture was allowed to cool to room temperature and was concentrated under reduced pressure. The residue was dissolved in methanol (40 mL) and 1 M aqueous hydrochloric acid (20 mL) was added. The mixture was heated at 50° C. for 6 hours. The mixture was allowed to stand at room temperature overnight and a white precipitate formed that was removed by filtration. The methanol was removed under reduced pressure and chloroform (20 mL) was added. The aqueous phase was adjusted to pH 12 with 1 M aqueous sodium hydroxide. The aqueous phase was extracted with chloroform (3×10 mL). The organic phases were combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The material was purified by chromatography using a HORIZON HPFC system (silica gel, gradient elution with 10-35% CMA in chloroform). The appropriate fractions were combined and concentrated under reduced pressure to provide a solid that was triturated with acetonitrile, crystallized from acetonitrile, and purified again by chromatography as described above using 5-40% CMA in chloroform as the eluent to provide 32 mg of N-{4-[4-amino-2-({[ethylideneamino]oxy}methyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl]butyl}benzamide as a white powder and as a mixture (approximately 1:1 mixture) of oxime isomers, mp 192.0-194.0° C.

Workup

  1. temperatureto cool to room temperature
  2. concentrationwas concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in methanol (40 mL)
  4. addition1 M aqueous hydrochloric acid (20 mL) was added
  5. temperatureThe mixture was heated at 50° C. for 6 hours
  6. customa white precipitate formed
  7. customthat was removed by filtration
  8. customThe methanol was removed under reduced pressure and chloroform (20 mL)
  9. additionwas added
  10. extractionThe aqueous phase was extracted with chloroform (3×10 mL)
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customThe material was purified by chromatography
  15. washa HORIZON HPFC system (silica gel, gradient elution with 10-35% CMA in chloroform)
  16. concentrationconcentrated under reduced pressure
  17. customto provide a solid
  18. customthat was triturated with acetonitrile
  19. customcrystallized from acetonitrile
  20. custompurified again by chromatography

Sources & evidence

ORD record
ord-b5929b2910c4409a8d435fab26a1b248
Source dataset
uspto-grants-2011_03
Patent number
US07897767B2

Reaction notes

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