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

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Reaction Conditions

Reaction Steps

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).

Provenance & Evidence