Phosphorus pentachloride → HCID 59799756, compound

HRID 2074464Notes

Reaction equation

HRID 2074464 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]([NH:13][C:14]2[CH:19]=[C:18]([N+:20]([O-:22])=[O:21])[CH:17]=[CH:16][C:15]=2[NH:23][CH:24]2[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]2)=O)=[CH:6][CH:5]=1)[CH3:2].P(Cl)(Cl)(Cl)(Cl)Cl>C(Cl)(Cl)Cl>[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]2[N:23]([CH:24]3[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]3)[C:15]3[CH:16]=[CH:17][C:18]([N+:20]([O-:22])=[O:21])=[CH:19][C:14]=3[N:13]=2)=[CH:6][CH:5]=1)[CH3:2]

Participants

4

Reactant 2

HCID 24819Phosphorus pentachlorideHCID 59799751HCID 59799751, compound

Product 1

HCID 59799756HCID 59799756, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

2-(4-Ethoxy-phenyl)-N-[2-(1-methyl-piperidin-4-ylamino)-5-nitro-phenyl]-acetamide 53 (190 mg, 0.461 mmol), Phosphorous pentachloride (100.7 mg, 0.483 mmol) were dissolved in anhydrous chloroform (10 mL) in a small, argon purged flask fitted with an condenser and magnetic stirbar. The solution was heated to reflux in an oil bath for 4 hours and cooled to room temperature overnight. The solid that had precipitated from the reaction mixture was collected on a sintered glass funnel and washed with a small amount of chloroform. The sticky solid was washed off the funnel in methanol and concentrated to residue. The residue was taken up in H2O and chloroform and 2M ammonium hydroxide solution added to adjust pH to 9-10. The mixture was transferred to a separatory funnel and the organic layer collected. The aqueous layer was further extracted with chloroform and the combined organic layers were washed with brine, dried over magnesium sulphate, filtered and concentrated to afford crude. The product was purified using silica gel column chromatography eluting with a solvent system of 5% 2M NH3 in methanol/95% dichloromethane to afford a pale yellow oil 54 2-(4-Ethoxy-benzyl)-1-(1-methyl-piperidin-4-yl)-5-nitro-1H-benzimidazole Yield: 127 mg (70.0%). 1H NMR (DMSO) δ: 1.29 (t, 3H, J=7.0), 1.39 (br d, 2H, J=9.8), 1.89-1.97 (m, 2H), 2.19 (s, 3H), 2.20-2.31 (m, 2H), 2.82 (br d, 2H, J=11.2), 3.96 (q, 2H, J=7.0), 4.29-4.37 (m, 1H), 4.37 (s, 2H), 6.87 (d, 2H, J=8.7), 7.17 (d, 2H, J=8.4), 7.82 (d, 1H, J=9.0), 8.07 (dd, 1H, J=9.0, 2.4), 8.48 (d, 1H, J=2.3); MS (ESI): 395 (MH+, 100%).

Workup

  1. customfitted with an condenser
  2. temperatureThe solution was heated
  3. temperatureto reflux in an oil bath for 4 hours
  4. customThe solid that had precipitated from the reaction mixture
  5. customwas collected on a sintered glass funnel
  6. washwashed with a small amount of chloroform
  7. washThe sticky solid was washed off the funnel in methanol
  8. concentrationconcentrated to residue
  9. additionchloroform and 2M ammonium hydroxide solution added
  10. customThe mixture was transferred to a separatory funnel
  11. customthe organic layer collected
  12. extractionThe aqueous layer was further extracted with chloroform
  13. washthe combined organic layers were washed with brine
  14. dry with materialdried over magnesium sulphate
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customto afford crude
  18. customThe product was purified
  19. washeluting with a solvent system of 5% 2M NH3 in methanol/95% dichloromethane

Sources & evidence

ORD record
ord-ce90ba76c0aa4dad9b5ce75394b901e5
Source dataset
uspto-grants-2011_04
Patent number
US07919510B2

Reaction notes

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