反応 #74528

反応方程式

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

N,N,N′,N′-tetramethylnaphthalene-1,8-diamine

1-chloroethyl chloroformate

→

title compound

4-[2-(1-azetidin-3-yl-1H-pyrazol-5-yl)-4-chlorophenoxy]-2,5-difluoro-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide

溶媒

dichloromethane

methanol

反応条件

後処理

1. 1
   濃縮The solution was concentrated in vacuo
2. 2
   その他the residue was partitioned between ethyl acetate (40 ml) and 1M aqueous citric acid solution (20 ml)
3. 3
   洗浄the ethyl acetate was washed with water
4. 4
   乾燥dried over anhydrous sodium sulphate
5. 5
   その他evaporated
6. 6
   その他the solvents removed in vacuo
7. 7
   その他to give an oil
8. 8
   温度refluxed for 5 hours
9. 9
   その他Some of the methanol was removed in vacuo
10. 10
    その他to leave about 5 ml
11. 11
    その他the precipitated solid was removed by filtration
12. 12
    その他dried
13. 13
    その他to purification by column chromatography on silica gel using 10-25% v/v methanol (
14. 14
    workup.ADDITIONcontaining 10% v/v 0.880 aqueous ammonia) in dichloromethane

実験手順

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.

出典