Synthetic processes and synthetic intermediates

Inventors

Ghone, Sanjeevani • Kang, Fu-An • Jain, Nareshkumar • Parhi, Ajit K. • Ponnaiah, Ravi • Soni, Anil Kumar • Athunuri, Siva Rami Reddy • Korrakuti, Thrisulapani • Seelam, Pullarao

Assignees

TAXIS PHARMACEUTICALS Inc

Abstract

The invention provides synthetic intermediates and synthetic processes that are useful for preparing the antibacterial agent TXA709:

Core Innovation

The disclosed invention provides synthetic intermediates and synthetic processes to prepare the antibacterial agent TXA709. The material is presented with emphasis on preparing TXA709 on a commercial scale and improving yield, and the routes connect defined intermediates through intermediate-to-intermediate transformations.

The description focuses on converting a compound of formula 7 to a compound of formula 8, and reacting a compound of formula 3 with a compound of formula 8 to provide a compound of formula 9. The disclosed pathway links formation of upstream formula-defined compounds to the subsequent conversion and coupling steps that lead to compound of formula 9 and then TXA709.

The routes also include preparation routes for earlier intermediates through reactions and reductions involving a nitro precursor, including preparing a compound of formula 2 from a nitro compound of formula 1. Reaction-condition ranges and named reagents/catalysts are provided for embodiments along the sequence, including hydrogenation and coupling agents such as EDC·HCl/DMAP.

Claims Coverage

The independent claims cover three process stages in the synthetic sequence: preparing TXA709 from an amide of formula 9 on a commercial scale, preparing a compound of formula 9 by reacting compounds of formulas 3 and 8 on a commercial scale, and preparing a compound of formula 8 by converting a compound of formula 7. Across these, the claims identify multiple inventive features including specific intermediate-to-intermediate transformations and reaction-type constraints for reduction, hydrogenation, carboxylating, and benzylating.

Overall, the claims define a sequential process where a compound of formula 7 is converted to compound of formula 8, compounds of formulas 3 and 8 are reacted to provide an amide of formula 9, and the amide of formula 9 is converted to TXA709 on a commercial scale. The dependent claim features further define reduction, hydrogenation, carboxylating, and benzylating steps, together with method constraints for the formula 3-to-formula 9 step and the formula 7-to-formula 8 step.

Stated Advantages

Documented Applications