Cyclopentylamine → 1-[(2-chloropyridin-4-yl)methyl]-3-[1-(N-cyclopentylglycyl)-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl]-5,5-dimethylimidazolidine-2,4-dione

HRID 546559Notes

Reaction equation

HRID 546559 reaction equation
Cl[CH2:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([N:14]3[C:18](=[O:19])[C:17]([CH3:21])([CH3:20])[N:16]([CH2:22][C:23]4[CH:28]=[CH:27][N:26]=[C:25]([Cl:29])[CH:24]=4)[C:15]3=[O:30])[CH:12]=2)[C:7]([CH3:32])([CH3:31])[CH2:6]1)=[O:4].[CH:33]1([NH2:38])[CH2:37][CH2:36][CH2:35][CH2:34]1>>[Cl:29][C:25]1[CH:24]=[C:23]([CH2:22][N:16]2[C:17]([CH3:20])([CH3:21])[C:18](=[O:19])[N:14]([C:11]3[CH:12]=[C:13]4[C:8]([C:7]([CH3:32])([CH3:31])[CH2:6][N:5]4[C:3](=[O:4])[CH2:2][NH:38][CH:33]4[CH2:37][CH2:36][CH2:35][CH2:34]4)=[CH:9][CH:10]=3)[C:15]2=[O:30])[CH:28]=[CH:27][N:26]=1

Participants

3

Reactant 2

HCID 2906CyclopentylamineHCID 576259893-[1-(chloroacetyl)-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl]-1-[(2-chloropyridin-4-yl)methyl]-5,5-dimethylimidazolidine-2,4-dione

Product 1

HCID 576260251-[(2-chloropyridin-4-yl)methyl]-3-[1-(N-cyclopentylglycyl)-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl]-5,5-dimethylimidazolidine-2,4-dione

Procedure

A solution of 3.423 g of 3-[1-(chloroacetyl)-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl]-1-[(2-chloropyridin-4-yl)methyl]-5,5-dimethylimidazolidine-2,4-dione obtained in stage j) below in 42 mL of cyclopentylamine is heated at 70° C. for 4 hours. The reaction mixture is then concentrated under reduced pressure and the residue is taken up in 100 mL of water and extracted with three times 60 mL of ethyl acetate. The combined organic phases are then washed with water, dried over magnesium sulphate, 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 (95/5 by volume) to give 3.5 g of 1-[(2-chloropyridin-4-yl)methyl]-3-[1-(N-cyclopentylglycyl)-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl]-5,5-dimethylimidazolidine-2,4-dione, the characteristics of which are as follows:

Workup

  1. concentrationThe reaction mixture is then concentrated under reduced pressure
  2. extractionextracted with three times 60 mL of ethyl acetate
  3. washThe combined organic phases are then washed with water
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is purified by chromatography on a column of silica
  8. washeluting with a mixture of dichloromethane and methanol (95/5 by volume)

Sources & evidence

ORD record
ord-dc5bc83b896345a5aca91a01ad58f054
Source dataset
uspto-grants-2011_05
Patent number
US07935819B2

Reaction notes

Loading…