Process for the synthesis of 4,5,6,7-tetrachloro-3′,6′-dihydroxy-2′,4′,5′,7′-tetraiodo-3H-spiro[isobenzofuran-1,9′-xanthen]-3-one(Rose Bengal) and related xanthenes

摘要

A new process for the manufacture of iodinated xanthenes in high purity includes a cyclization step followed by an iodination step. No extraction, chromatographic or solvent concentration steps are required, and the intermediate as well as final compounds are isolated via filtration or similar means. The process requires a single organic solvent, and the steps are completed at temperatures below 100° C. The exclusion of chloride ions, of chloride free-radicals, hypochlorite ions, or hypochlorous acid as reagents or from reagents that may generate these species in situ in the presence of oxidants, prevents undesirable impurity formation. Several new compounds have been conceived and isolated using these methods. These new compounds are also formed into new medicaments.

主权项

1. A compound of Formula 4 wherein R1 is independently F, Cl, Br, I, H or C1-C4 alkyl; R2, R3, R4, and R5 are independently Cl, H or I wherein three variables among the groups of R2, R3, R4, and R5 represent I and the other represents Cl or H; R6 is independently H or C1-C4 alkyl; R11 and R12 are independently H or a counter-ion capable of forming a pharmaceutically acceptable salt; and all tautomers thereof; atropisomers thereof; closed lactones thereof; enantiomers thereof;pharmaceutically acceptable salts thereof; and mixtures thereof for the chemotherapeutic treatment of human and animal tissue