Sodium Iodide → HCID 10186210, compound

HRID 1795909Notes

Reaction equation

HRID 1795909 reaction equation
[CH3:1][C@H:2]1[CH2:7][NH:6][C@H:5]([CH3:8])[CH2:4][N:3]1[C@H:9]([C:18]1[CH:19]=[C:20]([CH:28]=[CH:29][CH:30]=1)[C:21]([N:23]([CH2:26][CH3:27])[CH2:24][CH3:25])=[O:22])[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[CH:11]=1.[I-].[Na+].C(=O)([O-])[O-].[Na+].[Na+].[F:39][C:40]1[CH:41]=[C:42]([CH:45]=[CH:46][CH:47]=1)[CH2:43]Br>C(#N)C>[CH2:24]([N:23]([CH2:26][CH3:27])[C:21](=[O:22])[C:20]1[CH:28]=[CH:29][CH:30]=[C:18]([C@@H:9]([N:3]2[CH2:4][C@@H:5]([CH3:8])[N:6]([CH2:43][C:42]3[CH:45]=[CH:46][CH:47]=[C:40]([F:39])[CH:41]=3)[CH2:7][C@@H:2]2[CH3:1])[C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[CH:11]=2)[CH:19]=1)[CH3:25]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 680073-Fluorobenzyl bromideHCID 69104037HCID 69104037, compound

Product 1

HCID 10186210HCID 10186210, compoundYield 59.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 3-((αR)-α-((2S,5R)-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide (0.49 g, 1.20 mmol) in acetonitrile (10 mL) was added to sodium iodide (100 mg), sodium carbonate (0.70 g, 6.64 mmol) and stirred under nitrogen at room temperature during the addition of 3-fluorobenzyl bromide (0.16 mL, 1.32 mmol). The reaction was complete in 3 hours. The solvent was removed by evaporation and the residue was partitioned between methylene chloride and water. The aqueous layer was extracted with methylene chloride twice more, and the combined organic extracts were dried (Na2SO4/MgSO4) and concentrated under reduced pressure. The residual brown oil was purified by chromatography on silica gel (EtOAc/CH2Cl2) to give 0.37 g (0.71 mmol) of the desired product as a light brown amorphous solid. The salt was made by dissolving the amine in ethanol and titrating to pH 3.92 with 0.2 M HCl in ethanol. The salt was redissolved in water and lyophilized to obtain a light brown powdery solid. 1H NMR (300 MHz, CDCl3): δ 1.04–1.22 (m, 12H); 1.93–2.08 (m, 2H); 2.51–2.76 (m, 5H); 3.10–3.60 (m, 4H); 3.78 (s, 3H); 3.84–3.89 (d, J=13.3 Hz, 1H); 5.11 (s, 1H); 6.76–7.46 (m, 12H).

Workup

  1. customThe solvent was removed by evaporation
  2. customthe residue was partitioned between methylene chloride and water
  3. extractionThe aqueous layer was extracted with methylene chloride twice more
  4. dry with materialthe combined organic extracts were dried (Na2SO4/MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe residual brown oil was purified by chromatography on silica gel (EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-41107665b53e4b93b3bf904885157e5e
Source dataset
uspto-grants-2006_04
Patent number
US07030124B2

Reaction notes

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