To develop a strategy to control benzene, an ICH Q3C Class 1 impurity that may be present in spray solvents at ppm concentration, in amorphous polymer-stabilized spray-dried dispersion (SDD) products.

A practical synthesis of the SGLT-2 inhibitor β-C-aryl-d-glucoside (1) has been developed. The route employed 2,3,4,6-tetra-O-trimethlysilyl-d-glucano-1,5-lactone as the key chiral building block, prepared efficiently from the commercially available, inexpensive raw materials, d-gluconolactone and trimethylsilyl chloride. The salient step in the synthesis is the Lewis acid-mediated stereoselective reduction of a methyl C-aryl peracetylated glycoside using a silyl hydride to set the stereochemistry of the crucial anomeric chiral center. Several novel cocrystalline complexes of 1 with l-phenylalanine and l-proline were discovered. Single-crystal structures of these complexes and several synthetic intermediates have been determined. The l-phenylalanine complex was developed and used to purify and isolate the API. All steps were implemented at multikilogram scale.

The synthesis of a new conducting polymer via electrolysis of 2-vinylpyrrole is described. Characterization based on FTIR spectral analysis and electrical conductivity leads us to propose aromatic coupling of the pyrrole rings of adjacent poly(2-vinylpyrrole) chains to form cross-links. This polymer exhibits an electrical conductivity of approximately 10(-5) S/cm. Radical polymerization of the same monomer leads to a linear product which reacts with iodine to give an iodinated, slightly conducting polymer (8 x 10(-7) S/cm).