Indole → HCID 16108205, compound

HRID 2042905Notes

Reaction equation

HRID 2042905 reaction equation
S1C=CN=C1.N1C2C(=CC=CC=2)C=C1.[NH:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:17]([CH2:24][C:25]([OH:27])=[O:26])=[CH:16]1.N1C2C(=CC=CC=2)CC1.C(O)(C(F)(F)F)=O.[O:44]=[CH:45][C@@H:46]([C@H:48]([C@@H:50]([C@@H:52]([CH2:54][OH:55])[OH:53])[OH:51])[OH:49])O.C(OC(=O)C)(=O)C>CO.N1C=CC=CC=1>[C@@H:54]1([N:15]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17]([CH2:24][C:25]([OH:27])=[O:26])=[CH:16]2)[O:55][C@H:46]([CH2:45][OH:44])[C@@H:48]([OH:49])[C@H:50]([OH:51])[C@H:52]1[OH:53]

Participants

10

Reactant 7

HCID 798IndoleHCID 802Indole-3-Acetic AcidHCID 6422Trifluoroacetic acidHCID 7918Acetic AnhydrideHCID 9256ThiazoleHCID 10328Indoline2×HCID 107526(2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal

Product 1

HCID 16108205HCID 16108205, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1049PyridineSolvent

Procedure

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.

Workup

  1. customAfter hydrolysis, peracetylation of the tetrahydroxy groups

Sources & evidence

ORD record
ord-6de16745f95c48c29f1548098cd8731f
Source dataset
uspto-grants-2013_11
Patent number
US08586550B2

Reaction notes

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