Cesium carbonate → 3-(4-Tert-butylphenyl)-5,5-dimethyl-1-[(2-{[6-(pyrrolidin-1-yl-methyl)pyridin-3-yl]amino}pyridin-4-yl)methyl]imidazolidine-2,4-dione

HRID 546640Notes

Reaction equation

HRID 546640 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.Br[C:29]1[CH:30]=[CH:31][C:32]([CH2:35][N:36]2[CH2:40][CH2:39][CH2:38][CH2:37]2)=[N:33][CH:34]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[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:29]4[CH:34]=[N:33][C:32]([CH2:35][N:36]5[CH2:37][CH2:38][CH2:39][CH2:40]5)=[CH:31][CH:30]=4)[CH:7]=3)[C:10]2=[O:27])=[CH:22][CH:21]=1)([CH3:26])([CH3:25])[CH3:24]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 230909345-Bromo-2-(pyrrolidin-1-ylmethyl)pyridineHCID 576260021-[(2-Aminopyridin-4-yl)methyl]-3-(4-tert-butylphenyl)-5,5-dimethylimidazolidine-2,4-dione

Product 1

HCID 576260073-(4-Tert-butylphenyl)-5,5-dimethyl-1-[(2-{[6-(pyrrolidin-1-yl-methyl)pyridin-3-yl]amino}pyridin-4-yl)methyl]imidazolidine-2,4-dioneYield 8.9%

Reagents, catalysts & solvents 2

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

Procedure

To a solution of 0.5 g 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, 0.32 g of 5-bromo-2-(pyrrolidin-1-ylmethyl)pyridine obtained in stage a) below, 77 mg of 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (xantphos), 38 mg of palladium acetate and 1.75 g of caesium carbonate. The reaction mixture is refluxed for 7 hours and then filtered and concentrated under reduced pressure. The residue is purified by chromatography on a column of silica, eluting with a mixture of dichloromethane and methanol (87/13 by volume) to give 62 mg of 3-(4-tert-butylphenyl)-5,5-dimethyl-1-[(2-{[6-(pyrrolidin-1-yl-methyl)pyridin-3-yl]amino}pyridin-4-yl)methyl]imidazolidine-2,4-dione, the characteristics of which are as follows:

Workup

  1. temperatureThe reaction mixture is refluxed for 7 hours
  2. filtrationfiltered
  3. concentrationconcentrated under reduced pressure
  4. customThe residue is purified by chromatography on a column of silica
  5. washeluting with a mixture of dichloromethane and methanol (87/13 by volume)

Sources & evidence

ORD record
ord-ece5538c4bc54c98b9783594e2341428
Source dataset
uspto-grants-2011_05
Patent number
US07935819B2

Reaction notes

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