反应详情

4-(4-chloro-2-{1-[1-(diphenylmethyl)azetidin-3-yl]-1H-pyrazol-5-yl}phenoxy)-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide (Preparation 688, 270 mg, 0.321 mmol) was dissolved in dichloromethane (15 ml) and N,N,N′,N′-tetramethylnaphthalene-1,8-diamine (85 mg, 0.40 mmol) was added followed by 1-chloroethyl chloroformate (0.07 ml, 0.65 mmol) and the solution was stirred at room temperature for 4 hours. The solution was concentrated in vacuo and the residue was partitioned between ethyl acetate (40 ml) and 1M aqueous citric acid solution (20 ml), the ethyl acetate was washed with water, dried over anhydrous sodium sulphate, evaporated and the solvents removed in vacuo to give an oil. The oil was dissolved in methanol (15 ml) and refluxed for 5 hours. Some of the methanol was removed in vacuo to leave about 5 ml, the precipitated solid was removed by filtration and the filtrate was adsorbed onto silica gel (5 g) and dried prior to purification by column chromatography on silica gel using 10-25% v/v methanol (containing 10% v/v 0.880 aqueous ammonia) in dichloromethane. This afforded the title compound as a pinkish solid, 80 mg.

1. concentrationThe solution was concentrated in vacuo
2. customthe residue was partitioned between ethyl acetate (40 ml) and 1M aqueous citric acid solution (20 ml)
3. washthe ethyl acetate was washed with water
4. dry with materialdried over anhydrous sodium sulphate
5. customevaporated
6. customthe solvents removed in vacuo
7. customto give an oil
8. temperaturerefluxed for 5 hours
9. customSome of the methanol was removed in vacuo
10. customto leave about 5 ml
11. customthe precipitated solid was removed by filtration
12. customdried
13. customto purification by column chromatography on silica gel using 10-25% v/v methanol (
14. additioncontaining 10% v/v 0.880 aqueous ammonia) in dichloromethane