An improved synthesis of anticancer benzothiopyranoindazoles. An efficient large-scale β-aminoethylation procedure†

Improved processes for the synthesis of bulk quantities of the benzothiopyranoindazole clinical agent CI-958 and A-ring congeners is reported. The process chosen for scale-up operations achieves β-aminoethylation of an anilino precursor via a three-step sequence (acylation, reduction, deprotection) starting from N-(trityl)glycine. Detailed analytical data are reported for the target compounds and most intermediates, and detailed spectroscopy is given for CI-958.