Radhe K. Vaid

Synthesis, Crystallization, and Biological Evaluation of an Orally Active Prodrug of Gemcitabine

The design, synthesis, and biological characterization of an orally active prodrug (3) of gemcitabine are described. Additionally, the identification of a novel co-crystal solid form of the compound is presented. Valproate amide 3 is orally bioavailable and releases gemcitabine into the systemic circulation after passing through the intestinal mucosa. The compound has entered clinical trials and is being evaluated as a potential new anticancer agent.

Propane Phosphonic Acid Anhydride: A Mild Reagent for β-Lactam Synthesis

Abstract The use of propane phosphonic acid anhydride (T3P) as an acid activating reagent was demonstrated in the syntheses of cis β-lactams from the reactions of a glycine Dane salt and various imines.

Use of an iodonium ylide in the synthesis of p-nitrobenzyl (6R, 7S) 3-hydroxy-8-oxo-7-phenoxyacetamino-1-azabicyclo[4.2.0]octa-2-ene-2-carboxylate

Abstract p-Nitrobenzyl (6R,7S)-3-hydroxy-8-oxo-7-phenoxyacetamido-1-azabicyclo [4.2.0]octa-2-ene-2-carboxyate ( 6 ) was synthesized utilizing rhodium(II)- or acid-catalyzed cyclization of iodonium ylide ( 5 ). The iodonium ylide ( 5 ) was easily prepared from the corresponding β-keto ester ( 4 ) and [(diacetoxy)iodo]benzene in good yield.

Mechanistic investigation of a Ru-catalyzed direct asymmetric reductive amination reaction for a batch or continuous process scale-up: an industrial perspective

A comprehensive assessment of a Ru-catalyzed direct asymmetric reductive amination (DARA) reaction for producing an intermediate for an active pharmaceutical ingredient (API) was carried out. Experiments were conducted to investigate the impact of process parameters (such as reaction temperature, time, concentration, pressure, Ru-catalyst concentration, acid catalyst, and reagent stoichiometry) on chemo- and stereo-selectivity, and yield. An analysis of experimental data led to the development of a mechanistic mathematical model that was mathematically consistent with data from laboratory development and manufacturing campaigns. A combinatory approach outlined herein could be used to provide the optimum conditions for the DARA process. Furthermore, the feasible operating region was mapped out, which highlighted the complexity of the investigated chemistry and aided in developing the control strategy and regulatory submission package pertinent to this reaction. The efforts allowed the process to be successfully validated and scaled using a plug flow reactor (PFR) to manufacture 3200 kg of (S)-7,9-dimethyl-N-(2-methyl-2H-tetrazol-5-yl)-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-amine under current Good Manufacturing Practice (cGMP).