Tetrazolyl-phenyl actamide glucokinase activators

Patent Tetrazolyl-Phenyl Actamide Glucokinase Activators 

Sidduri, US Patent 6,441,180 (August 27, 2002) Assignee Hoffmann-La Roche Inc. 

V- Ethyl alcohol, sodium hydroxide vi- Triphenylphosphine, CH2CI2, N-bromosuccinimide, 2-aminothiazole 

A solution of 2-fluoro-4-iodoaniline (20 mmol) in 20 ml THE was cooled to 0°C, treated with acetic anhydride (80 mmol), and stirred at 0°C for 10 min and then for 2 hours at ambient temperature. The mixture was concentrated, the residue precipitated using 50 ml apiece diethyl ether and hexanes, and the product isolated in 92% yield, mp = 152-154 °C. Elemental analysis and MS data supplied. 

The product from Step 1 (18.24 mmol) was dissolved in 100 ml acetonitrile, cooled to 0 °C, and NaN3 (54.7 mmol) and trifluoromethanesulfonic anhydride (48 mmol) added. The mixture was warmed to 25 °C, stirred overnight, concentrated, and treated with 100 ml apiece EtOAc and water. The organic extracts were washed with brine, dried, and concentrated. The product was purified by flash chromatography on silica gel using hexanes/EtOAc, and the product isolated in 62% yield, mp = 122-124 °C. Elemental analysis and MS data supplied. 

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Patent Tetrazolyl-Phenyl Actamide Glucokinase Activators... 

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