Potassium Iodide → A-349821 free base

HRID 429239Notes

Reaction equation

HRID 429239 reaction equation
Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[O:19])=[CH:14][CH:13]=2)=[CH:8][CH:7]=1.Cl.[CH3:27][C@@H:28]1[CH2:32][CH2:31][C@@H:30]([CH3:33])[NH:29]1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CC(=O)CC>[CH3:27][C@@H:28]1[CH2:32][CH2:31][C@@H:30]([CH3:33])[N:29]1[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[O:19])=[CH:14][CH:13]=2)=[CH:8][CH:7]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 12268509(2R,5R)-2,5-dimethylpyrrolidine hydrochlorideHCID 155418504-{[4'-(3-Chloropropoxy)[1,1'-biphenyl]-4-yl]carbonyl}morpholine

Product 1

HCID 9954017A-349821 free baseYield 70%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Procedure

The product from Example 10E (30 mg, 0.084 mmol), (2R,5R)-2,5-dimethylpyrrolidine hydrochloride (50 mg, 0.5 mmol) (purchased from Toronto Research Chemicals, TRC), 75 mg of potassium carbonate and 75 mg of potassium iodide in 5 mL of 2-butanone were heated at 80° C. for 72 hours. The mixture was allowed to cool to ambient temperature, filtered and the filtrate was evaporated under reduced pressure. The residue was purified by HPLC chromatography (C18 reverse phase Water's 25 mm module prep column, 10 to 95% acetonitrile/0.1% TFA in water, 10 minute linear gradient, flow rate 40 mL/minute) to provide the title compound (70% yield).

Workup

  1. filtrationfiltered
  2. customthe filtrate was evaporated under reduced pressure
  3. customThe residue was purified by HPLC chromatography (C18 reverse phase Water's 25 mm module prep column, 10 to 95% acetonitrile/0.1% TFA in water, 10 minute linear gradient, flow rate 40 mL/minute)

Sources & evidence

ORD record
ord-a88369258da74ae2954a32ed59707b7f
Source dataset
uspto-grants-2001_11
Patent number
US06316475B1

Reaction notes

Loading…