Triphenylphosphine → HCID 57576721, compound

HRID 1907948Notes

Reaction equation

HRID 1907948 reaction equation
[CH3:1][C:2]1[N:7]2N=N[N:10]=[C:6]2[C:5]2[N:11]=[C:12]([CH2:27][O:28][N:29]=[C:30]([CH3:32])[CH3:31])[N:13]([CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19](=[O:26])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:4]=2[C:3]=1[CH3:33].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClC1C=CC=CC=1Cl>[NH2:10][C:6]1[C:5]2[N:11]=[C:12]([CH2:27][O:28][N:29]=[C:30]([CH3:31])[CH3:32])[N:13]([CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19](=[O:26])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:4]=2[C:3]([CH3:33])=[C:2]([CH3:1])[N:7]=1

Participants

4

Reactant 2

HCID 11776TriphenylphosphineHCID 86627655HCID 86627655, compound

Product 1

HCID 57576721HCID 57576721, compoundYield 47.9%

Reagents, catalysts & solvents 1

HCID 72391,2-DichlorobenzeneSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of N-{4-[5,6-dimethyl-8-({[(1-methylethylidene)amino]oxy}methyl)-7H-imidazo[4,5-c]tetraazolo[1,5-a]pyridin-7-yl]butyl}benzamide (1.9 g, 4.2 mmol), triphenylphosphine (2.2 g, 8.4 mmol), and 1,2-dichlorobenzene (40 mL) was heated at 125° C. for 2 days. The reaction was allowed to cool to room temperature and was concentrated under reduced pressure. The residue was dissolved in methanol (20 mL) and 1 M aqueous hydrochloric acid (20 mL) and heated at 40° C. for 6 hours. The reaction was allowed to stand at room temperature overnight and a white precipitate formed that was removed by filtration. The filtrate was concentrated under reduced pressure and the residue was partitioned between 1 M aqueous hydrochloric acid (20 mL) and chloroform (10 mL). The aqueous layer was extracted with chloroform (3×10 mL). The organic layers were combined, washed with saturated aqueous sodium carbonate, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The solid was purified by chromatography using a HORIZON HPFC system (an automated, modular high-performance flash purification product available from Biotage, Inc, Charlottesville, Va., USA) (silica gel, gradient elution with 10-35% CMA in chloroform, where CMA is 80:18:2 chloroform/methanol/concentrated ammonium hydroxide). The appropriate fractions were combined and concentrated under reduced pressure. The solid was triturated with ethyl acetate and was isolated by filtration, washed with ethyl acetate, and dried under vacuum at 50° C. overnight to provide 0.85 g of N-{4-[4-amino-6,7-dimethyl-2-({[(1-methylethylidene)amino]oxy}methyl)-1H-imidazo[4,5-c]pyridin-1-yl]butyl}benzamide as a white powder, mp 206.0-208.0° C. Anal. Calcd for C23H30N6O2.0.06 CHCl3: C, 64.46; H, 7.05; N, 19.56. Found: C, 64.31; H, 7.06; N, 19.55.

Workup

  1. temperatureto cool to room temperature
  2. concentrationwas concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in methanol (20 mL)
  4. temperature1 M aqueous hydrochloric acid (20 mL) and heated at 40° C. for 6 hours
  5. customa white precipitate formed
  6. customthat was removed by filtration
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe residue was partitioned between 1 M aqueous hydrochloric acid (20 mL) and chloroform (10 mL)
  9. extractionThe aqueous layer was extracted with chloroform (3×10 mL)
  10. washwashed with saturated aqueous sodium carbonate
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customThe solid was purified by chromatography
  15. custommodular high-performance flash purification product available from Biotage, Inc, Charlottesville, Va
  16. wash, USA) (silica gel, gradient elution with 10-35% CMA in chloroform, where CMA is 80:18:2 chloroform/methanol/concentrated ammonium hydroxide)
  17. concentrationconcentrated under reduced pressure
  18. customThe solid was triturated with ethyl acetate
  19. customwas isolated by filtration
  20. washwashed with ethyl acetate
  21. customdried under vacuum at 50° C. overnight

Sources & evidence

ORD record
ord-e8872af9b16747ccb54537ccec0a70dc
Source dataset
uspto-grants-2013_12
Patent number
US08598192B2

Reaction notes

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