N,N-Dimethylaniline → HCID 68156097, compound

HRID 1877796Notes

Reaction equation

HRID 1877796 reaction equation
P(Cl)(Cl)([Cl:3])=O.[Cl:6][C:7]1[CH:8]=[CH:9][C:10]2[NH:16][C:15](=O)[C:14]3=[CH:18][C:19]([CH3:21])=[CH:20][N:13]3[CH2:12][C:11]=2[CH:22]=1.CN(C)C1C=CC=CC=1>C1(OC)C=CC=CC=1>[Cl:6][C:7]1[CH:8]=[CH:9][C:10]2[N:16]=[C:15]([Cl:3])[C:14]3=[CH:18][C:19]([CH3:21])=[CH:20][N:13]3[CH2:12][C:11]=2[CH:22]=1

Participants

5

Reactant 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 68155891HCID 68155891, compound

Product 1

HCID 68156097HCID 68156097, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 7519AnisoleSolvent

Conditions

Temperature
82.5 °C

Procedure

Under a N2 atmosphere add phosphoryl chloride (124 g, 819 mmol) to a mixture of 7-chloro-2-methyl-5,10-dihydro-11H-pyrrolo[2,1-c][1,4]benzodiazepin-11-one (100 g, 405 mmol), N,N-dimethylaniline (138 g, 1.14 mol) and anisole (550 mL). Heat to 80-85° C. and stir for 4 hr. to 6 hr. Concentrate to a total of 1.5 volumes to 2.5 volumes while maintaining the temperature below 75° C. Cool to 15-25° C. Add dichloromethane (600 mL) dropwise and stir for 1 hr. Add the resulting mixture to water (600 mL) while maintaining the temperature between 10° C. and 35° C. Stir for 1 hr. and then separate the layers. Extract the aqueous layer with dichloromethane (600 mL). Wash the combined organic layers with 1.0 N HCl (600 g) followed by 7% NaHCO3 (600 g). Filter the organic layer through diatomite (20 g to 30 g) and silica gel (60 g to 100 g). Concentrate the resulting filtrate to a total of 1.5 volumes to 2.5 volumes while maintaining the temperature below 45° C. Add heptane (270 g to 410 g) and concentrate the resulting filtrate to a total of 1.5 volumes to 2.5 volumes while maintaining the temperature below 45° C. Add heptane (150 g to 210 g), cool to 5° C. to 10° C., and stir for 2 hr. to 3 hr. Filter, rinse the filter the cake with heptane, and dry under vacuum, at below 45° C., to obtain the title compound as a pale yellow solid (90% to 95% yield)

Workup

  1. waitto 6 hr
  2. concentrationConcentrate to a total of 1.5 volumes to 2.5 volumes
  3. temperaturewhile maintaining the temperature below 75° C
  4. temperatureCool to 15-25° C
  5. stirringAdd dichloromethane (600 mL) dropwise and stir for 1 hr
  6. additionAdd the resulting mixture to water (600 mL)
  7. temperaturewhile maintaining the temperature between 10° C. and 35° C
  8. stirringStir for 1 hr
  9. customand then separate the layers
  10. extractionExtract the aqueous layer with dichloromethane (600 mL)
  11. washWash the combined organic layers with 1.0 N HCl (600 g)
  12. filtrationFilter the organic layer through diatomite (20 g to 30 g) and silica gel (60 g to 100 g)
  13. concentrationConcentrate the resulting filtrate to a total of 1.5 volumes to 2.5 volumes
  14. temperaturewhile maintaining the temperature below 45° C
  15. concentrationAdd heptane (270 g to 410 g) and concentrate the resulting filtrate to a total of 1.5 volumes to 2.5 volumes
  16. temperaturewhile maintaining the temperature below 45° C
  17. temperatureAdd heptane (150 g to 210 g), cool to 5° C. to 10° C.
  18. stirringstir for 2 hr
  19. waitto 3 hr
  20. filtrationFilter
  21. washrinse the
  22. filtrationfilter the cake with heptane
  23. customdry under vacuum, at below 45° C.

Sources & evidence

ORD record
ord-c9fe511288b3499cb81e28fd8198f487
Source dataset
uspto-grants-2012_11
Patent number
US08314092B2

Reaction notes

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