Phosphorus pentachloride → HCID 59799749, compound

HRID 2074455Notes

Reaction equation

HRID 2074455 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][CH2:24][CH2:25][CH:26]2[CH2:30][CH2:29][CH2:28][N:27]2[CH3:31])=O)=[CH:6][CH:5]=1)[CH3:2].P(Cl)(Cl)(Cl)(Cl)Cl>C(Cl)(Cl)Cl.O.[OH-].[NH4+]>[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]2[N:23]([CH2:24][CH2:25][CH:26]3[CH2:30][CH2:29][CH2:28][N:27]3[CH3:31])[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

6

Reactant 2

HCID 24819Phosphorus pentachlorideHCID 59799758HCID 59799758, compound

Product 1

HCID 59799749HCID 59799749, compoundYield 38.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6212ChloroformSolvent2×HCID 14923Ammonium HydroxideSolvent

Procedure

2-(4-Ethoxy-phenyl)-N-{2-[2-(1-methyl-pyrrolidin-2-yl)-ethylamino]-5-nitro-phenyl}-acetamide 33 (60 mg, 0.141 mmol), Phosphorous pentachloride (33 mg, 0.158 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 4.5 hours and cooled to room temperature overnight. The mixture was diluted with 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 solid 34 2-(4-Ethoxy-benzyl)-1-[2-(1-methyl-pyrrolidin-2-yl)-ethyl]-5-nitro-1H-benzimidazole Yield: 22 mg (38.3%). 1H NMR (DMSO) δ; 1.29 (t, 3H, J=7.0), 1.38-1.51 (m, 2H), 1.51-1.70 (m, 3H), 1.75-1.87 (m, 1H), 1.96-2.05 (m, 2H), 2.07 (s, 3H), 2.85-2.95 (m, 1H), 3.97 (q, 2H, J=7.0), 4.21 (t, 2H, J=7.9), 4.32 (s, 2H), 6.87 (d, 2H, J=8.5), 7.19 (d, 2H, J=8.5), 7.70 (d, 1H, J=9.0), 8.14 (dd, 1H, J=8.9, 2.1), 8.47 (d, 1H, J=2.1); MS (ESI): 409 (MH+, 100%).

Workup

  1. customfitted with an condenser
  2. temperatureThe solution was heated
  3. temperatureto reflux in an oil bath for 4.5 hours
  4. additionadded
  5. customThe mixture was transferred to a separatory funnel
  6. customthe organic layer collected
  7. extractionThe aqueous layer was further extracted with chloroform
  8. washthe combined organic layers were washed with brine
  9. dry with materialdried over magnesium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto afford crude
  13. customThe product was purified
  14. washeluting with a solvent system of 5% 2M NH3 in methanol/95% dichloromethane

Sources & evidence

ORD record
ord-d52d181e50e54fd8b8b1e7262cc2d910
Source dataset
uspto-grants-2011_04
Patent number
US07919510B2

Reaction notes

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