Triphenylphosphine → HCID 57576704, compound

HRID 1907951Notes

Reaction equation

HRID 1907951 reaction equation
[CH3:1][C:2]1[N:7]2N=N[N:10]=[C:6]2[C:5]2[N:11]=[C:12]([CH2:24][O:25][N:26]=[C:27]([CH3:29])[CH3:28])[N:13]([CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19](=[O:23])[CH:20]([CH3:22])[CH3:21])[C:4]=2[C:3]=1[CH3:30].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]([CH2:24][O:25][N:26]=[C:27]([CH3:29])[CH3:28])[N:13]([CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19](=[O:23])[CH:20]([CH3:22])[CH3:21])[C:4]=2[C:3]([CH3:30])=[C:2]([CH3:1])[N:7]=1

Participants

4

Reactant 2

HCID 11776TriphenylphosphineHCID 86627656HCID 86627656, compound

Product 1

HCID 57576704HCID 57576704, compound

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}-2-methylpropanamide (from Part C, approximately 9.71 mmol), triphenylphosphine (5.1 g, 19 mmol), and 1,2-dichlorobenzene (97 mL) was heated at 125° C. for 2 days, then stirred at room temperature for 3 days, then heated at 130° C. for 5 hours. The reaction was allowed to cool to room temperature and was concentrated under reduced pressure. The residue was dissolved in methanol (80 mL) and 1 M aqueous hydrochloric acid (40 mL) and heated at 40° C. for 6 hours. The reaction was allowed to stir 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 bicarbonate, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The solid was purified by chromatography using a HORIZON HPFC system (silica gel, gradient elution with 5-55% CMA in chloroform). The appropriate fractions were combined and concentrated under reduced pressure. The resulting solid was triturated with acetonitrile and then was recrystallized from acetonitrile to provide N-{4-[4-amino-6,7-dimethyl-2-({[(1-methylethylidene)amino]oxy}methyl)-1H-imidazo[4,5-c]pyridin-1-yl]butyl}-2-methylpropanamide as a white powder, mp 180.0-181.0° C. Anal. Calcd for C20H32N6O2: C, 61.83; H, 8.30; N, 21.63. Found: C, 61.65; H, 8.65; N, 21.70.

Workup

  1. temperatureheated at 130° C. for 5 hours
  2. temperatureto cool to room temperature
  3. concentrationwas concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in methanol (80 mL)
  5. temperature1 M aqueous hydrochloric acid (40 mL) and heated at 40° C. for 6 hours
  6. stirringto stir at room temperature overnight
  7. customa white precipitate formed
  8. customthat was removed by filtration
  9. concentrationThe filtrate was concentrated under reduced pressure
  10. customthe residue was partitioned between 1 M aqueous hydrochloric acid (20 mL) and chloroform (10 mL)
  11. extractionThe aqueous layer was extracted with chloroform (3×10 mL)
  12. washwashed with saturated aqueous sodium bicarbonate
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure
  16. customThe solid was purified by chromatography
  17. washa HORIZON HPFC system (silica gel, gradient elution with 5-55% CMA in chloroform)
  18. concentrationconcentrated under reduced pressure
  19. customThe resulting solid was triturated with acetonitrile
  20. customwas recrystallized from acetonitrile

Sources & evidence

ORD record
ord-db9d30f3749949008af774e1d1affc99
Source dataset
uspto-grants-2013_12
Patent number
US08598192B2

Reaction notes

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