Sodium Iodide → HCID 10255673, compound

HRID 445029Notes

Reaction equation

HRID 445029 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:24]1[CH:25]=[C:26]([CH:38]=[CH:39][CH:40]=1)[C:27]([N:29]([C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[CH:32]=1)[CH3:30])=[O:28])[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([O:16]S(C(F)(F)F)(=O)=O)[CH:11]=1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[Na+].Br[CH2:50][CH2:51][CH2:52][F:53]>C(#N)C>[CH3:1][C@H:2]1[CH2:7][N:6]([CH2:50][CH2:51][CH2:52][F:53])[C@H:5]([CH3:8])[CH2:4][N:3]1[C@H:9]([C:24]1[CH:25]=[C:26]([CH:38]=[CH:39][CH:40]=1)[C:27]([N:29]([C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[CH:32]=1)[CH3:30])=[O:28])[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([OH:16])[CH:11]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 67699Propane, 1-bromo-3-fluoro-HCID 87996855HCID 87996855, compound

Product 1

HCID 10255673HCID 10255673, compoundYield 64.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

3-((alpha-R)-alpha-((2S,5R)-2,5-Dimethyl-1-piperazinyl)-3-(trifluoromethylsulfonyloxy)-benzyl)-N-(3-fluorophenyl)-N-methylbenzamide (from Example 5, 0.70 g, 1.2 mmol) was combined with anhydrous sodium carbonate powder (0.65 g, 6.1 mmol), 10 mL anhydrous acetonitrile, sodium iodide (0.03 g, 0.2 mmol), and 1-bromo-3-fluoropropane (0.12 mL, 1.3 mmol). The reaction was stirred for three days at room temperature under nitrogen, and then concentrated under reduced pressure. The residue was suspended in 15 mL ethanol, 10 mL of 10% w/v aqueous NaOH solution was added, and the reaction was stirred 2 hours at room temperature. The ethanol was removed under vacuum and the residue was partitioned between water and dichloromethane. The solution was adjusted to pH 8.5 using 3 N HCl, separated and extracted again with dichloromethane (2×15 mL). The solution was dried (Na2SO4/MgSO4) and concentrated under reduced pressure. The residual oil was purified by chromatography on silica gel (EtOAc+2% NH4OH/CH2Cl2) to give 0.39 g (0.77 mmol) of the desired product as an off-white foam. 1H NMR (600 MHz, d6-DMSO): δ 9.28 (s, 1H), 7.17-7.24 (m, 5H), 7.04-7.07 (m, 2H), 6.97 (dt, J=2.2, 8.4 Hz, 1H), 6.88 (dd, J=1.2, 8.0 Hz, 1H), 6.61 (dd, J=1.8, 8.0 Hz, 1H), 6.55 (s, 1H), 6.41 (d, J=7.4 Hz, 1H), 4.74 (br s, 1H), 4.42 (dt, J=47.5, 6.0 Hz, 2H), 3.30 (s, 3H), 2.70 (dd, J=2.9, 11.0 Hz, 1H), 2.55-2.61 (m, 1H), 2.48-2.52 (m, 1H—partially obscured by DMSO peak), 2.38-2.42 (m, 1H), 2.26 (br d, J˜9.2 Hz, 1H), 2.19-2.24 (m, 1H), 2.00 (dd, J=7.3, 10.8 Hz, 1H), 1.70-1.75 (m, 1H), 1.64-1.70 (m, 2H), 0.95 (d, J=6.2 Hz, 3H), 0.86 (d, J=6.2, Hz, 3H). Calculated for C30H35F2N3O2: C, 70.98; H, 6.95; N, 8.28; F, 7.48%. Found: C, 70.78; H, 7.23; N, 8.19; F, 7.24%.

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionwas added
  3. stirringthe reaction was stirred 2 hours at room temperature
  4. customThe ethanol was removed under vacuum
  5. customthe residue was partitioned between water and dichloromethane
  6. customseparated
  7. extractionextracted again with dichloromethane (2×15 mL)
  8. dry with materialThe solution was dried (Na2SO4/MgSO4)
  9. concentrationconcentrated under reduced pressure
  10. customThe residual oil was purified by chromatography on silica gel (EtOAc+2% NH4OH/CH2Cl2)

Sources & evidence

ORD record
ord-5a9995c14f0c457688fdbf08b1f47620
Source dataset
uspto-grants-2013_07
Patent number
US08476280B2

Reaction notes

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