Hydrochloric Acid → 1-Piperazinepropanoic acid, 4-(7-chloro-2-methyl-5H-pyrrolo[2,1-c][1,4]benzodiazepin-11-yl)-alpha,alpha-dimethyl-

HRID 1877808Notes

Reaction equation

HRID 1877808 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([N:12]3[CH2:17][CH2:16][N:15]([CH2:18][C:19]([CH3:25])([CH3:24])[C:20]([O:22]C)=[O:21])[CH2:14][CH2:13]3)[C:9]3=[CH:26][C:27]([CH3:29])=[CH:28][N:8]3[CH2:7][C:6]=2[CH:30]=1.[OH-].[Na+].Cl>C(O)(C)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([N:12]3[CH2:13][CH2:14][N:15]([CH2:18][C:19]([CH3:25])([CH3:24])[C:20]([OH:22])=[O:21])[CH2:16][CH2:17]3)[C:9]3=[CH:26][C:27]([CH3:29])=[CH:28][N:8]3[CH2:7][C:6]=2[CH:30]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 68155976HCID 68155976, compound

Product 1

HCID 601485641-Piperazinepropanoic acid, 4-(7-chloro-2-methyl-5H-pyrrolo[2,1-c][1,4]benzodiazepin-11-yl)-alpha,alpha-dimethyl-Yield 98%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
70 °C

Procedure

To a suspension of methyl 3-[4-(7-chloro-2-methyl-5H-pyrrolo[2,1-c][1,4]benzodiazepin-11-yl)piperazin-1-yl]-2,2-dimethylpropanoate (28.0 g, 65.27 mmoles) in a mixture of isopropyl alcohol (150 mL) and water (150 mL) add sodium hydroxide (3 equiv; 7.83 g, 195.82 mmoles) and heat at 70° C. for 4 h to give a clear solution. Heat at 70° C. for a further 1 h then cool slightly. Add 5M hydrochloric acid to give pH 8 and precipitate a white solid. Add further 5M hydrochloric acid to give a pH between 6.5 and 7. Reduce the volume of solvent by half and then chill the flask in a fridge for 0.5 h. Collect the resulting white solid by filtration and dry overnight in a vacuum oven at 40° C. over phosphorus pentoxide to give 3-[4-(7-chloro-2-methyl-5H-pyrrolo[2,1-c][1,4]benzodiazepin-11-yl)piperazin-1-yl]-2,2-dimethylpropanoic acid (26.5 g, 98% yield). MS (m/z): 415.3 (M+1). DSC melting point=246.5° C. (onset).

Workup

  1. customto give a clear solution
  2. temperatureHeat at 70° C. for a further 1 h
  3. temperaturethen cool slightly
  4. customto give pH 8
  5. customprecipitate a white solid
  6. additionAdd further 5M hydrochloric acid
  7. customto give a pH between 6.5 and 7
  8. temperaturechill the flask in a fridge for 0.5 h
  9. customCollect the resulting white solid
  10. filtrationby filtration
  11. dry with materialdry overnight in a vacuum oven at 40° C. over phosphorus pentoxide

Sources & evidence

ORD record
ord-72be7642541546589ef4b2648e085832
Source dataset
uspto-grants-2012_11
Patent number
US08314092B2

Reaction notes

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