N,N'-Dimethylethylenediamine → ethyl (10R,15S)-3-oxo-1,4,12-triazatetracyclo[7.6.1.05,16.010,15]hexadeca-5,7,9(16)-triene-12-carboxylate

HRID 1624924Notes

Reaction equation

HRID 1624924 reaction equation
[NH2:1][C:2](=[O:23])[CH2:3][N:4]1[C:12]2[C:11](Br)=[CH:10][CH:9]=[CH:8][C:7]=2[C@@H:6]2[CH2:14][N:15]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:16][CH2:17][C@H:5]12.C(=O)([O-])[O-].[K+].[K+].CNCCNC>O1CCOCC1>[O:23]=[C:2]1[CH2:3][N:4]2[C@H:5]3[CH2:17][CH2:16][N:15]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:14][C@H:6]3[C:7]3[C:12]2=[C:11]([CH:10]=[CH:9][CH:8]=3)[NH:1]1

Participants

5

Reactant 3

HCID 8070N,N'-Dimethylethylenediamine2×HCID 11430Potassium CarbonateHCID 59317961Ethyl (4aS,9bR)-5-(2-amino-2-oxoethyl)-6-bromo-1,3,4,4a,5,9b-hexahydro-2H-pyrido[4,3-b]indole-2-carboxylate

Product 1

HCID 20578971ethyl (10R,15S)-3-oxo-1,4,12-triazatetracyclo[7.6.1.05,16.010,15]hexadeca-5,7,9(16)-triene-12-carboxylate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A suspension of [4aS,9bR]-ethyl 5-(2-amino-2-oxoethyl)-6-bromo-3,4,4a,5-tetrahydro-1H-pyrido[4,3-b]indole-2(9bH)-carboxylate (254 mg, 1.34 mmol), cuprous iodide (254 mg, 1.34 mol), potassium carbonate (3.96 g, 28.7 mmol) and N,N′-dimethylethylenediamine (0.31 mL, 2.87 mmol) in dioxane (20 mL) is heated at reflux for 4.5 hours. Another portion of cuprous iodide (250 mg, 1.32 mmol) and N,N′-dimethylethylenediamine (0.33 mL, 3.05 mmol) is added. The resulting mixture is heated to a reflux for another 3 hours and then at 73° C. for about 66 hours. The reaction mixture is concentrated and passed through a short alumina column using 100:3:3 dichloromethan:triethylamine:methanol. The resulting solvent from the column is evaporated to a solid and redissolved in dichloromethane. The dichloromethane solution is washed with brine, dried with sodium phosphate and concentrated to a solid (3.7 g, 95%, 83% pure by HPLC).

Workup

  1. temperatureis heated
  2. temperatureat reflux for 4.5 hours
  3. temperatureThe resulting mixture is heated to
  4. temperaturea reflux for another 3 hours
  5. concentrationThe reaction mixture is concentrated
  6. customThe resulting solvent from the column is evaporated to a solid
  7. dissolutionredissolved in dichloromethane
  8. washThe dichloromethane solution is washed with brine
  9. dry with materialdried with sodium phosphate
  10. concentrationconcentrated to a solid (3.7 g, 95%, 83% pure by HPLC)

Sources & evidence

ORD record
ord-7239fdac06174c4b8576acd8a87b7aae
Source dataset
uspto-grants-2014_07
Patent number
US08779139B2

Reaction notes

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