Cesium carbonate → 3-(4-Tert-butylphenyl)-5,5-dimethyl-1-{[2-(pyrimidin-5-ylamino)pyridin-4-yl]methyl}imidazolidine-2,4-dione

HRID 546580Notes

Reaction equation

HRID 546580 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.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:36]1[CH:37]=[N:38][CH:39]=[N:40][CH:41]=1>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:36]4[CH:37]=[N:38][CH:39]=[N:40][CH:41]=4)[CH:8]=3)[C:11]2=[O:28])=[CH:23][CH:22]=1)([CH3:27])([CH3:26])[CH3:25]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 783445-BromopyrimidineHCID 671984711-[(2-Aminopyridin-4-yl)methyl]-3-(4-tert-butylphenyl)-5,5-dimethylimidazolidine-2,4-dione hydrochloride

Product 1

HCID 236303313-(4-Tert-butylphenyl)-5,5-dimethyl-1-{[2-(pyrimidin-5-ylamino)pyridin-4-yl]methyl}imidazolidine-2,4-dioneYield 61.2%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

To a solution of 200 mg of 1-[(2-aminopyridin-4-yl)methyl]-3-(4-tert-butylphenyl)-5,5-dimethylimidazolidine-2,4-dione hydrochloride obtained in stage c) below in 5 mL of dioxane are successively added under argon 11.1 mg of palladium diacetate, 29 mg of (9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine)(Xantphos), 777 mg of caesium carbonate and 86.8 mg of 5-bromopyrimidine. The reaction mixture is heated at 100° C. for 5 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, methanol and concentrated aqueous ammonia (95/4/1 by volume) to give 135 mg of 3-(4-tert-butylphenyl)-5,5-dimethyl-1-{[2-(pyrimidin-5-ylamino)pyridin-4-yl]methyl}imidazolidine-2,4-dione in the form of an off-white solid, 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 dichloromethane, methanol and concentrated aqueous ammonia (95/4/1 by volume)

Sources & evidence

ORD record
ord-a66c6b53b601491bb6495fdb3634ced0
Source dataset
uspto-grants-2011_05
Patent number
US07935819B2

Reaction notes

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