Cesium carbonate → 3-(4-Tert-butylphenyl)-1-({2-[(2-chloropyridin-3-yl)amino]pyridin-4-yl}methyl)-5,5-dimethylimidazolidine-2,4-dione

HRID 546627Notes

Reaction equation

HRID 546627 reaction equation
Cl.[NH2:2][C:3]1[CH:8]=[C:7]([CH2:9][N:10]2[C:14]([CH3:16])([CH3:15])[C:13](=[O:17])[N:12]([C:18]3[CH:23]=[CH:22][C:21]([C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:20][CH:19]=3)[C:11]2=[O:28])[CH:6]=[CH:5][N:4]=1.[Cl:29][C:30]1[C:35](I)=[CH:34][CH:33]=[CH:32][N:31]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C=CC(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=2OC2C1=CC=C(P(C1C=CC=CC=1)C1C=CC=CC=1)C=2>O1CCOCC1.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[C:24]([C:21]1[CH:20]=[CH:19][C:18]([N:12]2[C:13](=[O:17])[C:14]([CH3:16])([CH3:15])[N:10]([CH2:9][C:7]3[CH:6]=[CH:5][N:4]=[C:3]([NH:2][C:35]4[C:30]([Cl:29])=[N:31][CH:32]=[CH:33][CH:34]=4)[CH:8]=3)[C:11]2=[O:28])=[CH:23][CH:22]=1)([CH3:27])([CH3:26])[CH3:25]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 27357432-Chloro-3-iodopyridineHCID 671984711-[(2-Aminopyridin-4-yl)methyl]-3-(4-tert-butylphenyl)-5,5-dimethylimidazolidine-2,4-dione hydrochlorideHCID 86628973(9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine)

Product 1

HCID 576260283-(4-Tert-butylphenyl)-1-({2-[(2-chloropyridin-3-yl)amino]pyridin-4-yl}methyl)-5,5-dimethylimidazolidine-2,4-dione

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 0.8 g of 1-[(2-aminopyridin-4-yl)methyl]-3-(4-tert-butylphenyl)-5,5-dimethylimidazolidine-2,4-dione hydrochloride obtained in stage c) of Example 7 in 50 mL of dioxane are successively added under argon 0.628 g of 2-chloro-3-iodopyridine, 2.8 g of caesium carbonate, 150 mg of (9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine) (xantphos) and 49 mg of palladium diacetate. The reaction mixture is heated at 90° C. for 3 hours and then filtered, and the filtrate is concentrated under reduced pressure. The residue is purified by chromatography on a column of silica, eluting with a mixture of cyclohexane and ethyl acetate (70/30 by volume) to give 0.51 g of 3-(4-tert-butylphenyl)-1-({2-[(2-chloropyridin-3-yl)amino]pyridin-4-yl}methyl)-5,5-dimethylimidazolidine-2,4-dione, the characteristics of which are as follows:

Workup

  1. filtrationfiltered
  2. concentrationthe filtrate is concentrated under reduced pressure
  3. customThe residue is purified by chromatography on a column of silica
  4. washeluting with a mixture of cyclohexane and ethyl acetate (70/30 by volume)

Sources & evidence

ORD record
ord-567cbbe127aa43648ce59f6e1dc44ca8
Source dataset
uspto-grants-2011_05
Patent number
US07935819B2

Reaction notes

Loading…