反应详情

A solution of N-(2,4-dimethoxybenzyl)thiazol-2-amine (0.546 g, 2.182 mmol) in THF (7 mL) was cooled in a dry ice-acetone bath for 5 minutes. Lithium bis(trimethylsilyl)amide (1M in THF) (2.381 ml, 2.381 mmol) was added dropwise, then the flask was removed from the cooling bath for 5 min. The flask was again cooled into a dry ice-acetone bath for 20 min, resulting in the formation of a thick slurry. A suspension of 1-chloroisoquinoline-6-sulfonyl chloride (0.520 g, 1.984 mmol) in THF (5 mL) was added dropwise, then the cooling bath was removed. The reaction was stirred for one hour. The reaction was quenched with saturated ammonium chloride solution, diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The filtrate was purified by silica gel chromatography on a 40 g silica column with 0 to 30% EtOAc/Heptane. The product containing fractions were combined and concentrated to afford a white solid. The solid was triturated with methanol and stirred for five minutes. The solution was filtered and the solids were washed with methanol. The solids were dried under a vacuum to afford 1-chloro-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as a white solid. m/z (ESI) 498.1 (M+H)+.

1. customthe flask was removed from the cooling bath for 5 min
2. temperatureThe flask was again cooled into a dry ice-acetone bath for 20 min
3. customresulting in the formation of a thick slurry
4. additionwas added dropwise
5. customthe cooling bath was removed
6. customThe reaction was quenched with saturated ammonium chloride solution
7. additiondiluted with ethyl acetate
8. washwashed with water
9. extractionThe aqueous layer was extracted with ethyl acetate
10. dry with materialthe combined organic layers were dried with sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated
13. customThe filtrate was purified by silica gel chromatography on a 40 g silica column with 0 to 30% EtOAc/Heptane
14. additionThe product containing fractions
15. concentrationconcentrated
16. customto afford a white solid
17. customThe solid was triturated with methanol
18. stirringstirred for five minutes
19. filtrationThe solution was filtered
20. washthe solids were washed with methanol
21. customThe solids were dried under a vacuum