2-Bromoethyl isocyanate → (3aSR,10RS)-2-(2-Bromo-ethyl)-6-chloro-10-(3-hydroxy-phenyl)-3a-methyl-3a,4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta[b]fluorene-1,3-dione

HRID 41029Notes

Reaction equation

HRID 41029 reaction equation
CO[C:3]([C:5]1([CH3:26])[CH2:17][C:16]2[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([Cl:18])[CH:14]=3)[NH:9][C:8]=2[CH:7]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([OH:25])[CH:20]=2)[NH:6]1)=[O:4].[Br:27][CH2:28][CH2:29][N:30]=[C:31]=[O:32]>CC(=O)CC>[Br:27][CH2:28][CH2:29][N:30]1[C:31](=[O:32])[N:6]2[CH:7]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([OH:25])[CH:20]=3)[C:8]3[NH:9][C:10]4[C:15]([C:16]=3[CH2:17][C:5]2([CH3:26])[C:3]1=[O:4])=[CH:14][C:13]([Cl:18])=[CH:12][CH:11]=4

Participants

4

Reactant 2

HCID 42559572-Bromoethyl isocyanate2×HCID 68887684(1RS,3SR)-6-Chloro-1-(3-hydroxy-phenyl)-3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester

Product 1

HCID 68940637(3aSR,10RS)-2-(2-Bromo-ethyl)-6-chloro-10-(3-hydroxy-phenyl)-3a-methyl-3a,4,9,10-tetrahydro-2,9,10a-triaza-cyclopenta[b]fluorene-1,3-dioneYield 62%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of 1.66 g (5.39 mmol) (1RS,3SR)-6-Chloro-1-(3-hydroxy-phenyl)-3-methyl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester in 20 ml 2-butanon are added 490 μl 2-bromoethyl isocyanate. After heating the mixture to reflux for 4 h, additional 490 μl 2-bromoethyl isocyanate are added and the mixture is heated to reflux over night. The solvent is removed at reduced pressure and the residue is dissolved in 20 ml dimethyl formamide. The mixture is stirred at 80° C. for 15 h. The solvent is removed at reduced pressure and the residue is dissolved in ethyl acetate. Water is added and the organic layer is dried with magnesium sulfate. The solvent is removed at reduced pressure and the residue is suspended in a mixture of toluene and ethyl acetate (4:1). The suspension is filtered. 1.35 g (62%) of the title compound are obtained as the precipitate. m.p.: 262-264° C., MS: m/z (MH+)=488.0/490.0

Workup

  1. temperatureAfter heating the mixture
  2. temperatureto reflux for 4 h
  3. temperaturethe mixture is heated
  4. temperatureto reflux over night
  5. customThe solvent is removed at reduced pressure
  6. dissolutionthe residue is dissolved in 20 ml dimethyl formamide
  7. customThe solvent is removed at reduced pressure
  8. dissolutionthe residue is dissolved in ethyl acetate
  9. additionWater is added
  10. dry with materialthe organic layer is dried with magnesium sulfate
  11. customThe solvent is removed at reduced pressure
  12. additionthe residue is suspended in a mixture of toluene and ethyl acetate (4:1)
  13. filtrationThe suspension is filtered

Sources & evidence

ORD record
ord-cb7418d1062745db942610ce6cff63f6
Source dataset
uspto-grants-2013_09
Patent number
US08530493B2

Reaction notes

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