Potassium Iodide → 8-[3-((R)-2-Methyl-pyrrolidin-1-yl)-propoxy]-5,6-dihydro-2H-benzo[h]cinnolin-3-one

HRID 2042630Notes

Reaction equation

HRID 2042630 reaction equation
Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15](=[O:19])[NH:16][N:17]=3)[CH2:12][CH2:11][C:10]=2[CH:20]=1.[CH3:21][C@@H:22]1[CH2:26][CH2:25][CH2:24][NH2+:23]1.C1(S([O-])(=O)=O)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>C(#N)C>[CH3:21][C@@H:22]1[CH2:26][CH2:25][CH2:24][N:23]1[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15](=[O:19])[NH:16][N:17]=3)[CH2:12][CH2:11][C:10]=2[CH:20]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 596519418-(3-Chloro-propoxy)-5,6-dihydro-2H-benzo[h]cinnolin-3-oneHCID 86646919(R)-2-methylpyrrolidine benzene sulfonate

Product 1

HCID 596520248-[3-((R)-2-Methyl-pyrrolidin-1-yl)-propoxy]-5,6-dihydro-2H-benzo[h]cinnolin-3-one

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

In a 100 mL round bottom flask, 8-(3-chloro-propoxy)-5,6-dihydro-2H-benzo[h]cinnolin-3-one (600 mg, 2.1 mmol), benzenesulfonate (R)-2-methyl-pyrrolidinium (1.02 g, 4.2 mmol), potassium carbonate (1.14 g, 8.3 mmol), and potassium iodide (10 mg, 0.06 mmol) in acetonitrile (60 mL) was heated to reflux 14 h. The reaction was cooled and the solvent concentrated under vacuum. The slurry was partitioned between methylene chloride and water, and then washed with water three times. The organics were extracted three times with 3% citric acid solution. The combined aqueous layers were basified with sat. NaHCO3 sol. and extracted with methylene chloride, then dried over MgSO4. Ethereal HCl was added and the solvents reduced under vacuum. Crystallization from MeOH/Et2O produced 85 mg (11%). Mp 289-292° C. MS m/z 340 (M+H).

Workup

  1. temperatureto reflux 14 h
  2. temperatureThe reaction was cooled
  3. concentrationthe solvent concentrated under vacuum
  4. customThe slurry was partitioned between methylene chloride and water
  5. washwashed with water three times
  6. extractionThe organics were extracted three times with 3% citric acid solution
  7. extractionextracted with methylene chloride
  8. dry with materialdried over MgSO4
  9. additionEthereal HCl was added
  10. customCrystallization from MeOH/Et2O
  11. customproduced 85 mg (11%)

Sources & evidence

ORD record
ord-0b0984073f95483daf079c155cd4f8e3
Source dataset
uspto-grants-2013_11
Patent number
US08586588B2

Reaction notes

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