Potassium Carbonate → 4'-carboxymethoxy-N-(3-methoxy-5-methylpyrazin-2-yl)-2-biphenylsulphonamide

4'-Hydroxy- N-(isobutoxycarbonyl)- N-(3-methoxy-5-methylpyrazin-2-yl)-2-biphenylsulphonamide (0.5 g) was added to a solution of methyl bromoacetate (0.12 ml) in acetone (20 ml) containing potassium carbonate (0.166 g). The mixture was stirred for 18 hours and then heated under reflux for 1 hour and cooled. The solvent was removed by evaporation and water (20 ml) was added to the residue. The mixture was then extracted with ethyl acetate (2×20 ml). The combined organic extracts were washed successively with 2M sodium hydroxide solution (15 ml), water (20 ml) and brine (10 ml) and then dried (MgSO4). The solvent was removed by evaporation and the residue was dissolved in dimethoxyethane (5 ml) and methanol (5 ml). 2M Sodium hydroxide solution (1 ml) was added and the mixture was stirred for 18 hours and evaporated to dryness. Water (20 ml) was added to the residue and the mixture was washed with ethyl acetate (2×15 ml). The aqueous phase was acidified to pH2 with 2M hydrochloric acid and extracted with ethyl acetate (3×15 ml). The combined organic phases were extracted with saturated aqueous sodium bicarbonate solution (2×15 ml) and the combined aqueous phase was acidified with 6M hydrochloric acid and extracted with ethyl acetate (3×15 ml). The combined organic extracts were washed with water (15 ml) and brine (15 ml) and dried (MgSO4). The solvent was removed by evaporation and the residue crystallised from ether to give 4'-carboxymethoxy-N-(3-methoxy-5-methylpyrazin-2-yl)-2-biphenylsulphonamide (0.123 g) as a solid, m.p. 165°-166° C.; microanalysis found: C, 55.9; H, 4.5; N, 9.9%; C20H19N3O6S requires: C, 55.9; H, 4.46; N, 9.78%; 1H NMR (d6 -DMSO): 2.24 (s, 3H), 3.84 (s, 3H), 4.67 (s, 2H), 6.78-6.95 (m, 2H), 7.16 (d, 2H), 7.27 (d, 1H); 7.49-7.66 (m, 3H), 8.06 (d, 1H), 9.50 (br s, 1H); mass spectrum (-ve ESP): 428 (M-H)-.

1. temperatureheated
2. temperatureunder reflux for 1 hour
3. temperaturecooled
4. customThe solvent was removed by evaporation and water (20 ml)
5. additionwas added to the residue
6. extractionThe mixture was then extracted with ethyl acetate (2×20 ml)
7. washThe combined organic extracts were washed successively with 2M sodium hydroxide solution (15 ml), water (20 ml) and brine (10 ml)
8. dry with materialdried (MgSO4)
9. customThe solvent was removed by evaporation
10. dissolutionthe residue was dissolved in dimethoxyethane (5 ml)
11. addition2M Sodium hydroxide solution (1 ml) was added
12. stirringthe mixture was stirred for 18 hours
13. customevaporated to dryness
14. additionWater (20 ml) was added to the residue
15. washthe mixture was washed with ethyl acetate (2×15 ml)
16. extractionextracted with ethyl acetate (3×15 ml)
17. extractionThe combined organic phases were extracted with saturated aqueous sodium bicarbonate solution (2×15 ml)
18. extractionextracted with ethyl acetate (3×15 ml)
19. washThe combined organic extracts were washed with water (15 ml) and brine (15 ml)
20. dry with materialdried (MgSO4)
21. customThe solvent was removed by evaporation
22. customthe residue crystallised from ether

ORD record

ord-49da6b3ae47345fdaa70396cb3af19ff

Source dataset

uspto-grants-1997_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05668137