Indole → HCID 16108205, compound

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Reaction Steps

In order to accommodate need for SAR optimization of the thiazole derivatives, indoles at A ring may be synthesized and evaluated. One isomer of indole may be prepared by adopting the reported procedure [Kai, K. et al. Phytochemistry, 2007, 68, 2512-2522]. First, commercially available indole-3-acetic acid 73 is esterified under acidic conditions. Next, the indole ring of 74 is partially reduced to indoline 75 using triethylsilane and TFA in 77% yield. Condensation of 75 with D-glucose is accomplished in refluxed aqueous methanol in 88% yield. The product 76 is then acylated and oxidized to regenerate the indole ring in 40% over two steps (product 77). After hydrolysis, peracetylation of the tetrahydroxy groups using acetic anhydride and pyridine yields N-β-D-glucopyranosyl indole-3-acetic acid 78 in 40% yield for the two steps. As in Scheme 9, usual coupling between acid 78 and 2-amino-1-(furan-2-yl)ethanone in the presence of EDCI, HOBt, and NMM and then cyclization using Lawesson's reagent produce thiazole 79 in 59% yield for the two steps. Finally, treatment of the tetraacetate 79 with sodium methoxide generates the target compound 80 in 18% yield as shown in Scheme 17.

Provenance & Evidence