Diphosgene → 3-(1-Acetyl-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-5,5-dimethyl-1-pyridin-4-ylmethyl-imidazolidine-2,4-dione

HRID 2356957Notes

Reaction equation

HRID 2356957 reaction equation
O=C(Cl)[O:3][C:4](Cl)(Cl)Cl.[NH2:9][C:10]1[CH:18]=[C:17]2[C:13]([C:14]([CH3:23])([CH3:22])[CH2:15][N:16]2[C:19](=[O:21])[CH3:20])=[CH:12][CH:11]=1.[CH3:24][C:25]([NH:31][CH2:32][C:33]1[CH:38]=[CH:37][N:36]=[CH:35][CH:34]=1)([CH3:30])[C:26](OC)=[O:27]>ClCCCl.C1COCC1>[C:19]([N:16]1[C:17]2[C:13](=[CH:12][CH:11]=[C:10]([N:9]3[C:26](=[O:27])[C:25]([CH3:30])([CH3:24])[N:31]([CH2:32][C:33]4[CH:34]=[CH:35][N:36]=[CH:37][CH:38]=4)[C:4]3=[O:3])[CH:18]=2)[C:14]([CH3:23])([CH3:22])[CH2:15]1)(=[O:21])[CH3:20]

Participants

6

Reactant 3

HCID 10426DiphosgeneHCID 218651761-(6-Amino-3,3-dimethylindolin-1-yl)ethanoneHCID 43725938HCID 43725938, compound

Product 1

HCID 669158063-(1-Acetyl-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-5,5-dimethyl-1-pyridin-4-ylmethyl-imidazolidine-2,4-dione

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

7.26 g (36.7 mmol) of diphosgene were initially charged at −20° C. in 80 ml of 1,2-dichloroethane, and 3.0 g (14.5 mmol) of 1-(6-amino-3,3-dimethyl-2,3-dihydroindol-1-yl)ethanone, dissolved in 80 ml of 1,2-dichloroethane, were added dropwise. After stirring at RT for 2 h and reflux for 1 h, the mixture was concentrated fully. The remaining residue was dissolved in 80 ml of THF, added to a solution of 3.06 g (14.7 mmol) of methyl 2-methyl-2-[(pyridin-4-ylmethyl)amino]propionate in 80 ml of THF, and heated under reflux for 8 h. The residue remaining after evaporation was purified by means of preparative HPLC (RP18, acetonitrile/water, 0.1% TFA). Yield: 4.69 g.

Workup

  1. additionwere added dropwise
  2. temperaturereflux for 1 h
  3. concentrationthe mixture was concentrated fully
  4. dissolutionThe remaining residue was dissolved in 80 ml of THF
  5. temperatureheated
  6. temperatureunder reflux for 8 h
  7. customafter evaporation
  8. customwas purified by means of preparative HPLC (RP18, acetonitrile/water, 0.1% TFA)

Sources & evidence

ORD record
ord-8618c24646224636a7e831ecbd9196dc
Source dataset
uspto-grants-2010_07
Patent number
US07759379B2

Reaction notes

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