Hydrochloric Acid → HCID 57626032, compound

HRID 546612Notes

Reaction equation

HRID 546612 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]([CH3:41])([CH3:40])[CH2:22][N:23]4[C:26](=[O:39])[CH2:27][N:28]([CH:36]([CH3:38])[CH3:37])C(=O)OC(C)(C)C)=[CH:19][CH:18]=3)C2=O)[CH:5]=[CH:4][N:3]=1.[CH3:43][N:44]([CH3:48])[C:45]([NH2:47])=[O:46].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:91](=[O:94])([O-])[O-].[Cs+].[Cs+].Cl>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:36]([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:47][C:45](=[O:46])[N:44]([CH3:48])[CH3:43])[CH:7]=4)[C:91]3=[O:94])[CH:25]=2)[C:21]([CH3:40])([CH3:41])[CH2:22]1)=[O:39])([CH3:38])[CH3:37]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 11737N,N-DimethylureaHCID 57626012HCID 57626012, compoundHCID 86628973(9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine)

Product 1

HCID 57626032HCID 57626032, compoundYield 54.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of 400 mg of tert-butyl [2-(6-{3-[(2-chloropyridin-4-yl)methyl]-4,4-dimethyl-2,5-dioxoimidazolidin-1-yl}-3,3-dimethyl-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]isopropylcarbamate obtained in stage a) below in 15 mL of dioxane are successively added, under argon, 88 mg of N,N-dimethylurea, 39 mg of (9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine) (Xantphos), 30 mg of palladium acetate and 872 mg of caesium carbonate. The reaction mixture is refluxed for 4 hours and filtered, and the filtrate is concentrated under reduced pressure. The residue is taken up in 30 mL of ethyl acetate, washed with three times 15 mL of 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 (90/10 by volume) to give 280 mg of a yellow lacquer, which is taken up in 10 mL of a 4N solution of hydrogen chloride in dioxane and stirred for 17 hours at room temperature. The reaction mixture is then concentrated under reduced pressure and is triturated in 20 mL of ethyl ether and the solid formed is filtered off and dried to give 200 mg of 3-[4-({3-[1-(N-isopropylglycyl)-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl]-5,5-dimethyl-2,4-dioxoimidazolidin-1-yl}methyl)pyridin-2-yl]-1,1-dimethylurea in hydrochloride form, 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. washwashed with three times 15 mL of water
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is purified by chromatography on a column of silica
  9. washeluting with a mixture of dichloromethane and methanol (90/10 by volume)
  10. customto give 280 mg of a yellow lacquer, which
  11. concentrationThe reaction mixture is then concentrated under reduced pressure
  12. customis triturated in 20 mL of ethyl ether
  13. customthe solid formed
  14. filtrationis filtered off
  15. customdried

Sources & evidence

ORD record
ord-ec1b27ba55434c4db443da4af7ee666a
Source dataset
uspto-grants-2011_05
Patent number
US07935819B2

Reaction notes

Loading…