반응 #74528

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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

용매

dichloromethane

methanol

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후처리

1. 1
   농축The solution was concentrated in vacuo
2. 2
   기타the residue was partitioned between ethyl acetate (40 ml) and 1M aqueous citric acid solution (20 ml)
3. 3
   세척the ethyl acetate was washed with water
4. 4
   건조dried over anhydrous sodium sulphate
5. 5
   기타evaporated
6. 6
   기타the solvents removed in vacuo
7. 7
   기타to give an oil
8. 8
   온도refluxed for 5 hours
9. 9
   기타Some of the methanol was removed in vacuo
10. 10
    기타to leave about 5 ml
11. 11
    기타the precipitated solid was removed by filtration
12. 12
    기타dried
13. 13
    기타to 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

실험 절차

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.

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