Cesium carbonate → 3-(4-Tert-butylphenyl)-5,5-dimethyl-1-[2-(5-pyrrolidin-1-ylmethylpyridin-3-ylamino)pyridin-4-ylmethyl]imidazolidine-2,4-dione

HRID 546642Notes

Reaction equation

HRID 546642 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([CH2:8][N:9]2[C:13]([CH3:15])([CH3:14])[C:12](=[O:16])[N:11]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([CH3:26])([CH3:25])[CH3:24])=[CH:19][CH:18]=3)[C:10]2=[O:27])[CH:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:35]1[CH:36]=[N:37][CH:38]=[C:39]([CH2:41][N:42]2[CH2:46][CH2:45][CH2:44][CH2:43]2)[CH:40]=1>O1CCOCC1.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[C:23]([C:20]1[CH:19]=[CH:18][C:17]([N:11]2[C:12](=[O:16])[C:13]([CH3:15])([CH3:14])[N:9]([CH2:8][C:6]3[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:35]4[CH:36]=[N:37][CH:38]=[C:39]([CH2:41][N:42]5[CH2:43][CH2:44][CH2:45][CH2:46]5)[CH:40]=4)[CH:7]=3)[C:10]2=[O:27])=[CH:22][CH:21]=1)([CH3:26])([CH3:25])[CH3:24]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 212559453-Bromo-5-(pyrrolidin-1-ylmethyl)pyridineHCID 576260021-[(2-Aminopyridin-4-yl)methyl]-3-(4-tert-butylphenyl)-5,5-dimethylimidazolidine-2,4-dione

Product 1

HCID 671964313-(4-Tert-butylphenyl)-5,5-dimethyl-1-[2-(5-pyrrolidin-1-ylmethylpyridin-3-ylamino)pyridin-4-ylmethyl]imidazolidine-2,4-dioneYield 12.5%

Reagents, catalysts & solvents 2

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

Procedure

To a solution of 500 mg of 1-[(2-aminopyridin-4-yl)methyl]-3-(4-tert-butylphenyl)-5,5-dimethylimidazolidine-2,4-dione obtained in stage c) of Example 7 in 15 mL of dioxane are successively added, under argon, 46 mg of palladium diacetate, 95 mg of (9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine)(Xantphos), 1.8 g of caesium carbonate and 0.39 g of 3-Bromo-5-pyrrolidin-1-ylmethylpyridine obtained in stage a) below. The reaction mixture is refluxed for 4 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 dichloromethane and methanol (96/4 by volume) to give 90 mg of 3-(4-tert-butylphenyl)-5,5-dimethyl-1-[2-(5-pyrrolidin-1-ylmethylpyridin-3-ylamino)pyridin-4-ylmethyl]imidazolidine-2,4-dione, the characteristics of which are as follows:

Workup

  1. temperatureThe reaction mixture is refluxed for 4 hours
  2. filtrationfiltered
  3. concentrationthe filtrate is concentrated under reduced pressure
  4. customThe residue is purified by chromatography on a column of silica
  5. washeluting with a mixture of dichloromethane and methanol (96/4 by volume)

Sources & evidence

ORD record
ord-8090b0232ae64453be28884b982d93ef
Source dataset
uspto-grants-2011_05
Patent number
US07935819B2

Reaction notes

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