Acetone → HCID 131723144, compound

HRID 277708Notes

Reaction equation

HRID 277708 reaction equation
ClC1C(OC)=C(OC)C=CC=1[C:12]([N:14]([CH2:20][C:21]1[N:25]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[O:33][CH2:34][CH2:35][CH2:36]Cl)[C:24]2[CH:38]=[CH:39][CH:40]=[CH:41][C:23]=2[N:22]=1)[CH2:15][CH2:16][CH:17]([CH3:19])[CH3:18])=[O:13].[Na+].[I-].C[C:45]([CH3:47])=O>>[CH3:19][CH:17]([CH3:18])[CH2:16][CH2:15][N:14]([CH2:20][C:21]1[N:25]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[O:33][CH2:34][CH2:35][CH2:36][N:22]2[CH2:47][CH2:45][N:14]([CH3:12])[CH2:20][CH2:21]2)[C:24]2[CH:38]=[CH:39][CH:40]=[CH:41][C:23]=2[N:22]=1)[CH:12]=[O:13]

Participants

4

Reactant 3

HCID 180AcetoneHCID 5238Sodium Iodide2×HCID 11786713HCID 11786713, compound

Product 1

HCID 131723144HCID 131723144, compound

Procedure

A solution of 395 mg (0.66 mmole) of (2-chloro-3,4-dimethoxyphenyl)-N-[(1-{[2-(3-chloropropoxy)phenyl]-methyl}benzimidazol-2-yl)methyl]-N-(3-methylbutyl) carboxamide in 6 mL of acetone is treated with 99 mg (3.30 mmole) of NaI at reflux for 16 hrs, at which time another 3.30 mmole of NaI is added and heated for an additional 24 hrs. The solution is evaporated under reduced pressure, the residue is diluted with 30 mL of ethyl acetate, washed with 2×10 mL water and 1×10 mL brine, dried over anhydrous Na2SO4 and the solvent is removed in vacuo. The residue is dissolved in anhydrous 1-methyl-2-pyrrolidinone at 100 mg/ mL and 1 mL of the solution is treated with an excess of N-methyl piperazine at 50° C. for 16 hr. The resulting solution is cooled to room temperature, washed with 3×1 mL water and 1×1 mL brine, dried over anhydrous Na2SO4 and the solvent is removed in vacuo. The residue is prep-plate chromatographed (5% MeOH/CH2Cl2/0.5% NH4OH) to afford 65 mg (70%) of 2-chloro-3,4-dimethoxyphenyl)-N-(3-methylbutyl)-N-{[1-({2-[3-(4-methylpiperazinyl)propoxy]phenyl}methyl)benzimidazol-2-yl]methyl}carboxamide. Mass Spec M+ 663.

Workup

  1. additionis added
  2. temperatureheated for an additional 24 hrs
  3. customThe solution is evaporated under reduced pressure
  4. additionthe residue is diluted with 30 mL of ethyl acetate
  5. washwashed with 2×10 mL water and 1×10 mL brine
  6. dry with materialdried over anhydrous Na2SO4
  7. customthe solvent is removed in vacuo
  8. dissolutionThe residue is dissolved in anhydrous 1-methyl-2-pyrrolidinone at 100 mg/ mL and 1 mL of the solution
  9. additionis treated with an excess of N-methyl piperazine at 50° C. for 16 hr
  10. washwashed with 3×1 mL water and 1×1 mL brine
  11. dry with materialdried over anhydrous Na2SO4
  12. customthe solvent is removed in vacuo
  13. customThe residue is prep-plate chromatographed (5% MeOH/CH2Cl2/0.5% NH4OH)

Sources & evidence

ORD record
ord-d8940bd818ce4ed8803fad1cb9d61e67
Source dataset
uspto-grants-2002_03
Patent number
US06358949B1

Reaction notes

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