Acetonitrile → HCID 68155976, compound

HRID 1877800Notes

Reaction equation

HRID 1877800 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10](Cl)[C:9]3=[CH:13][C:14]([CH3:16])=[CH:15][N:8]3[CH2:7][C:6]=2[CH:17]=1.Cl.Cl.[CH3:20][C:21]([CH3:33])([CH2:26][N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1)[C:22]([O:24][CH3:25])=[O:23].C(NC(C)C)(C)C.C(#N)C>O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([N:30]3[CH2:29][CH2:28][N:27]([CH2:26][C:21]([CH3:33])([CH3:20])[C:22]([O:24][CH3:25])=[O:23])[CH2:32][CH2:31]3)[C:9]3=[CH:13][C:14]([CH3:16])=[CH:15][N:8]3[CH2:7][C:6]=2[CH:17]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 7912DiisopropylamineHCID 68155933Methyl 2,2-dimethyl-3-(piperazin-1-yl)propanoate dihydrochlorideHCID 68156097HCID 68156097, compound

Product 1

HCID 68155976HCID 68155976, compoundYield 98.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

Heat a mixture of 7,11-dichloro-2-methyl-5H-pyrrolo[2,1-c][1,4]benzodiazepine (10.0 g, 37.7 mmol), methyl 2,2-dimethyl-3-(piperazin-1-yl)-propionate dihydrochloride (19.4 g, 71.0 mmol), diisopropylamine (22.9 g, 226 mmol), and acetonitrile (80 g) at 80° C. to 85° C. for 22 hr. to 26 hr. Cool to 30° C. to 40° C. and add ethyl acetate (80 g). Add water (80 g) dropwise. Stir 40 min. to 60 min. and separate the layers. Extract the aqueous layer with ethyl acetate (60 g to 80 g). Wash the combined organic layers with 25% aqueous sodium chloride (2×40 g). Concentrate the organic layer to a total of 1.5 volumes and 3.5 volumes while maintaining the temperature below 50° C. Add heptane (41 g to 55 g) at 40° C. to 50° C.)\ and stir for 2 hr. to 3 hr. Concentrate to a total of 1.5 volumes to 3.0 volumes while maintaining the temperature below 50° C. Cool to 0° C. to 10° C. and stir for 2 hr. to 3 hr. Filter, wash the filtercake with heptane (3.0 g to 10.0 g), and dry under vacuum, at below 60° C., to afford the title compound (16.0 g, 94.7% w/w % assay, 94% yield) as a light, yellow solid.

Workup

  1. temperatureHeat
  2. temperatureCool to 30° C. to 40° C.
  3. customseparate the layers
  4. extractionExtract the aqueous layer with ethyl acetate (60 g to 80 g)
  5. washWash the combined organic layers with 25% aqueous sodium chloride (2×40 g)
  6. concentrationConcentrate the organic layer to a total of 1.5 volumes and 3.5 volumes
  7. temperaturewhile maintaining the temperature below 50° C
  8. stirringAdd heptane (41 g to 55 g) at 40° C. to 50° C.)\ and stir for 2 hr
  9. waitto 3 hr
  10. concentrationConcentrate to a total of 1.5 volumes to 3.0 volumes
  11. temperaturewhile maintaining the temperature below 50° C
  12. temperatureCool to 0° C. to 10° C.
  13. stirringstir for 2 hr
  14. waitto 3 hr
  15. filtrationFilter
  16. washwash the filtercake with heptane (3.0 g to 10.0 g)
  17. customdry under vacuum, at below 60° C.

Sources & evidence

ORD record
ord-b1a1965826684e1a8419d5ca241fc9ad
Source dataset
uspto-grants-2012_11
Patent number
US08314092B2

Reaction notes

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