Cesium carbonate → 4-[2-(6-aminopyridin-3-yl)-4-fluorophenoxy]-N-(5-chloro-1,3-thiazol-2-yl)-3-cyanobenzenesulfonamide

Participants

Reaction Conditions

Reaction Steps

Example 587 from above can be prepared as follows. N-(5-Chloro-1,3-thiazol-2-yl)-3-cyano-N-(2,4-dimethoxybenzyl)-4-(4-fluoro-2-iodophenoxy)benzenesulfonamide (Preparation 217, 100 mg, 0.146 mmol), 2-aminopyridine-5-boronic acid pinacol ester (35.4 mg, 0.161 mmol), palladium (0) tetrakis(triphenylphoshine) (17.3 mg, 0.015 mmol) and caesium carbonate (143 mg, 0.438 mmol) were charged to a 25 ml round-bottomed flask and purged with nitrogen (×3). To this was added fresh degassed 1,4-dioxane (4 ml) and fresh degassed water (1 ml) and the vessel was heated to 60° C. and stirred for 16 hours. The solvent was removed in vacuo and the residue was dissolved in methanol (2 ml) before loading on to a ISOLUTE™ SCX-2 cartridge (2 g). The cartridge was washed with methanol (50 ml) followed by ammonia (2 M in methanol, 50 ml). The basic washes were concentrated in vacuo and the residue was dissolved in dichloromethane (10 ml). To this solution was added trifluoroacetic acid (1 ml) and the solution stirred at room temperature for 18 hours before concentrating in vacuo. The residue was dissolved in methanol (2 ml) and loaded on to a ISOLUTE™ PE-AX cartridge (5 g). The cartridge was washed with methanol (3 column volumes) followed by formic acid (2% solution in methanol, 3 column volumes). The acidic washes were concentrated in vacuo to afford a sticky yellow solid which was triturated in dichloromethane to afford the title compound as a white solid.

Provenance & Evidence