Potassium Phosphate, Tribasic → 1-(2-Chloropyridin-4-yl)-3-(4-cyclopropylpyridin-3-yl)imidazolidin-2-one

HRID 572372Notes

Reaction equation

HRID 572372 reaction equation
CN[C@@H]1CCCC[C@H]1NC.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH:19]1([C:22]2[CH:27]=[CH:26][N:25]=[CH:24][C:23]=2[N:28]2[CH2:32][CH2:31][NH:30][C:29]2=[O:33])[CH2:21][CH2:20]1.[Cl:34][C:35]1[CH:40]=[C:39](I)[CH:38]=[CH:37][N:36]=1>C(Cl)(Cl)Cl.[Cu](I)I.CO.O1CCOCC1>[Cl:34][C:35]1[CH:40]=[C:39]([N:30]2[CH2:31][CH2:32][N:28]([C:23]3[CH:24]=[N:25][CH:26]=[CH:27][C:22]=3[CH:19]3[CH2:21][CH2:20]3)[C:29]2=[O:33])[CH:38]=[CH:37][N:36]=1

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 15165112-Chloro-4-iodopyridineHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 709820071-(4-Cyclopropylpyridin-3-yl)imidazolidin-2-one

Product 1

HCID 665764121-(2-Chloropyridin-4-yl)-3-(4-cyclopropylpyridin-3-yl)imidazolidin-2-oneYield 41%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 887MethanolSolventHCID 6212ChloroformSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

Copper iodide (6.5 mg, 0.034 mmol), trans-N,N′-dimethylcyclohexane-1,2-diamine (4.8 mg, 0.034 mmol) and potassium phosphate (219.3 mg, 1.034 mmol) were added to a solution of 1,4-dioxane (5 mL) previously purged with nitrogen (10 minutes). The reaction mixture was purged with argon for 10 minutes, followed by the addition of 1-(4-cyclopropylpyridin-3-yl)imidazolidin-2-one (I-1d: 70 mg, 0.344 mmol) and 2-chloro-4-iodopyridine (99.09 mg, 0.413 mmol). The reaction mixture was heated to reflux at 120° C. overnight. The reaction was monitored by TLC (10% MeOH in chloroform). The reaction mixture was cooled and partitioned between ethyl acetate and water. The organic layer was concentrated to yield the crude product. Purification by column chromatography on silica gel (2% methanol in CHCl3) afforded 42 mg of the product (41% yield).

Workup

  1. custompreviously purged with nitrogen (10 minutes)
  2. customThe reaction mixture was purged with argon for 10 minutes
  3. temperatureThe reaction mixture was heated
  4. temperatureThe reaction mixture was cooled
  5. custompartitioned between ethyl acetate and water
  6. concentrationThe organic layer was concentrated
  7. customto yield the crude product
  8. customPurification by column chromatography on silica gel (2% methanol in CHCl3)

Sources & evidence

ORD record
ord-f2edbe1e8fee4591a4c5bb0b6de01b1d
Source dataset
uspto-grants-2015_05
Patent number
US09029399B2

Reaction notes

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