3-Cyanobenzoic acid → (5s)-2-(3-Cyanophenyl)-4-(4-fluorophenyl)-4-(6-fluoro-3-pyridyl)-5-methyl-2-imidazoline

HRID 1455311Notes

Reaction equation

HRID 1455311 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6](O)=O)#[N:2].[Cl-].ClC1N(C)CC[NH+]1C.ClCCl.[F:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([C:36]2[CH:37]=[N:38][C:39]([F:42])=[CH:40][CH:41]=2)([NH2:35])[C@@H:32]([NH2:34])[CH3:33])=[CH:27][CH:26]=1.C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.C(N(CC)CC)C>[C:1]([C:3]1[CH:4]=[C:5]([C:6]2[NH:34][C@@H:32]([CH3:33])[C:31]([C:28]3[CH:29]=[CH:30][C:25]([F:24])=[CH:26][CH:27]=3)([C:36]3[CH:37]=[N:38][C:39]([F:42])=[CH:40][CH:41]=3)[N:35]=2)[CH:9]=[CH:10][CH:11]=1)#[N:2]

Participants

7

Reactant 4

HCID 158753-Cyanobenzoic acidHCID 516892Sodium BicarbonateHCID 58649654(2S)-1-(4-fluorophenyl)-1-(6-fluoro-3-pyridyl)-1,2-propanediamineHCID 690530322-Chloro-1,3-dimethylimidazolinium chloride dichloromethane

Product 1

HCID 178461604(5s)-2-(3-Cyanophenyl)-4-(4-fluorophenyl)-4-(6-fluoro-3-pyridyl)-5-methyl-2-imidazolineYield 98.5%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8471TriethylamineSolvent

Procedure

3-Cyanobenzoic acid (84 mg), triethylamine (159 μL) and. 2-chloro-1,3-dimethylimidazolinium chloride—dichloromethane 25% solution (212 μL) were added to a solution of (2S)-1-(4-fluorophenyl)-1-(6-fluoro-3-pyridyl)-1,2-propanediamine (100 mg) described in Reference Example 5-1 in chloroform (3 mL) in this order at 0° C. Then temperature of the mixture was raised to room temperature, and the mixture was stirred for 15 minutes. Saturated sodium hydrogen carbonate aqueous solution was added to the reaction mixture, and then the mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and dried over anhydrous sodium sulfate. Sodium sulfate was removed by filtration, and the organic solvent was evaporated in vacuo. The obtained crude product was stirred at 130° C. for 15 hours. The obtained oil was purified by silica gel column chromatography (C-300; hexane: ethyl acetate=1:1) to give the objective compound (140 mg).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated sodium chloride aqueous solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. customSodium sulfate was removed by filtration
  5. customthe organic solvent was evaporated in vacuo
  6. customThe obtained crude product
  7. stirringwas stirred at 130° C. for 15 hours
  8. customThe obtained oil was purified by silica gel column chromatography (C-300; hexane: ethyl acetate=1:1)

Sources & evidence

ORD record
ord-46601d0f6a5d4399a009658567818575
Source dataset
uspto-grants-2009_01
Patent number
US07482358B2

Reaction notes

Loading…