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

Temperature

60 °C

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.

1. customExample 587 from above can be prepared
2. custompurged with nitrogen (×3)
3. additionTo this was added fresh
4. customdegassed 1,4-dioxane (4 ml)
5. customfresh degassed water (1 ml)
6. customThe solvent was removed in vacuo
7. dissolutionthe residue was dissolved in methanol (2 ml) before loading on to a ISOLUTE™ SCX-2 cartridge (2 g)
8. washThe cartridge was washed with methanol (50 ml)
9. concentrationThe basic washes were concentrated in vacuo
10. dissolutionthe residue was dissolved in dichloromethane (10 ml)
11. additionTo this solution was added trifluoroacetic acid (1 ml)
12. stirringthe solution stirred at room temperature for 18 hours
13. concentrationbefore concentrating in vacuo
14. dissolutionThe residue was dissolved in methanol (2 ml)
15. washThe cartridge was washed with methanol (3 column volumes)
16. concentrationThe acidic washes were concentrated in vacuo
17. customto afford a sticky yellow solid which
18. customwas triturated in dichloromethane

ORD record

ord-f05621203d2741f09942d9220c1c5eea

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08907101B2