3-Aminopyridine → 3-[1-(N-isopropylglycyl)-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl]-5,5-dimethyl-1-{[2-(pyridin-3-ylamino)pyridin-4-yl]methyl}imidazolidine-2,4-dione

HRID 546610

Reaction equation

HRID 546610 reaction equation
Cl[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:25]=[C:24]4[C:20]([C:21]([CH3:34])([CH3:33])[CH2:22][N:23]4[C:26](=[O:32])[CH2:27][NH:28][CH:29]([CH3:31])[CH3:30])=[CH:19][CH:18]=3)[C:10]2=[O:35])[CH:5]=[CH:4][N:3]=1.[NH2:36][C:37]1[CH:38]=[N:39][CH:40]=[CH:41][CH:42]=1.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.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1CCCC1=O.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:29]([NH:28][CH2:27][C:26]([N:23]1[C:24]2[C:20](=[CH:19][CH:18]=[C:17]([N:11]3[C:12](=[O:16])[C:13]([CH3:15])([CH3:14])[N:9]([CH2:8][C:6]4[CH:5]=[CH:4][N:3]=[C:2]([NH:36][C:37]5[CH:38]=[N:39][CH:40]=[CH:41][CH:42]=5)[CH:7]=4)[C:10]3=[O:35])[CH:25]=2)[C:21]([CH3:34])([CH3:33])[CH2:22]1)=[O:32])([CH3:31])[CH3:30]

Participants

8

Reactant 4

HCID 100093-AminopyridineHCID 10796Cesium carbonateHCID 576259921-[(2-chloropyridin-4-yl)methyl]-3-[1-(N-isopropylglycyl)-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl]-5,5-dimethylimidazolidine-2,4-dioneHCID 86628973(9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine)

Product 1

HCID 576260313-[1-(N-isopropylglycyl)-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl]-5,5-dimethyl-1-{[2-(pyridin-3-ylamino)pyridin-4-yl]methyl}imidazolidine-2,4-dioneYield 12.6%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 249 mg of 1-[(2-chloropyridin-4-yl)methyl]-3-[1-(N-isopropylglycyl)-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl]-5,5-dimethylimidazolidine-2,4-dione obtained in stage a) below in 3 mL of N-methylpyrrolidinone are successively added, under argon, 94 mg of 3-aminopyridine, 29 mg of (9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine) (Xantphos), 22 mg of palladium acetate and 652 mg of caesium carbonate. The reaction mixture is heated at 140° C. for 1 hour by microwave, cooled to room temperature, diluted with 20 mL of dichloromethane and filtered, and the filtrate is concentrated under reduced pressure. The residue is triturated in 40 mL of water and the precipitate formed is filtered off and purified by chromatography on a column of silica, eluting with a mixture of dichloromethane and methanol (93/7 by volume) to give 35 mg of 3-[1-(N-isopropylglycyl)-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl]-5,5-dimethyl-1-{[2-(pyridin-3-ylamino)pyridin-4-yl]methyl}imidazolidine-2,4-dione, the characteristics of which are as follows:

Workup

  1. temperaturecooled to room temperature
  2. filtrationfiltered
  3. concentrationthe filtrate is concentrated under reduced pressure
  4. customThe residue is triturated in 40 mL of water
  5. customthe precipitate formed
  6. filtrationis filtered off
  7. custompurified by chromatography on a column of silica
  8. washeluting with a mixture of dichloromethane and methanol (93/7 by volume)

Sources & evidence

ORD record
ord-3b40de847d8e458c9c38022bf8a6f693
Source dataset
uspto-grants-2011_05
Patent number
US07935819B2

Linked notes

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