2,4-Pyridinedicarbonitrile → (5S)-2-(4-cyano-2-pyridyl)-4-(4-fluorophenyl)-4-(6-fluoro-3-pyridyl)-5-methyl-2-imidazoline

HRID 1455313Notes

Reaction equation

HRID 1455313 reaction equation
[C:1]([C:3]1[CH:8]=[C:7]([C:9]#[N:10])[CH:6]=[CH:5][N:4]=1)#[N:2].FC(F)(F)S([O-])(=O)=O.[Yb+3].FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O.[F:36][C:37]1[CH:42]=[CH:41][C:40]([C:43]([C:48]2[CH:49]=[N:50][C:51]([F:54])=[CH:52][CH:53]=2)(N)[C@@H:44]([NH2:46])[CH3:45])=[CH:39][CH:38]=1>C1(C)C=CC=CC=1.C(OCC)(=O)C>[C:9]([C:7]1[CH:6]=[CH:5][N:4]=[C:3]([C:1]2[NH:46][C@@H:44]([CH3:45])[C:43]([C:40]3[CH:41]=[CH:42][C:37]([F:36])=[CH:38][CH:39]=3)([C:48]3[CH:49]=[N:50][C:51]([F:54])=[CH:52][CH:53]=3)[N:2]=2)[CH:8]=1)#[N:10]

Participants

6

Reactant 3

HCID 1201442,4-PyridinedicarbonitrileHCID 2733225Ytterbium triflateHCID 58649654(2S)-1-(4-fluorophenyl)-1-(6-fluoro-3-pyridyl)-1,2-propanediamine

Product 1

HCID 178461606(5S)-2-(4-cyano-2-pyridyl)-4-(4-fluorophenyl)-4-(6-fluoro-3-pyridyl)-5-methyl-2-imidazolineYield 78.4%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

2,4-Dicyanopyridine (46.5 mg) and ytterbium trifluoromethanesulfonate (24 mg) were added to a solution of the optical active (2S)-1-(4-fluorophenyl)-1-(6-fluoro-3-pyridyl)-1,2-propanediamine (100 mg) described in Reference Example 5-1 in toluene (0.25 mL), and the mixture was stirred at 100° C. for 5 hours. The reaction mixture was diluted with ethyl acetate, washed with saturated sodium hydrogen carbonate aqueous solution, water and saturated sodium chloride aqueous solution in this order, and dried over anhydrous sodium sulfate. Sodium sulfate was removed by filtration, and the organic solvent was evaporated in vacuo. The obtained residue was purified by silica gel column chromatography (C-300; hexane: ethyl acetate=2:3) to give the objective compound (106 mg) as a white solid.

Workup

  1. washwashed with saturated sodium hydrogen carbonate aqueous solution, water and saturated sodium chloride aqueous solution in this order
  2. dry with materialdried over anhydrous sodium sulfate
  3. customSodium sulfate was removed by filtration
  4. customthe organic solvent was evaporated in vacuo
  5. customThe obtained residue was purified by silica gel column chromatography (C-300; hexane: ethyl acetate=2:3)

Sources & evidence

ORD record
ord-f3f7177c30c1402aa87329096b13a18c
Source dataset
uspto-grants-2009_01
Patent number
US07482358B2

Reaction notes

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