Lithium hexamethyldisilazane → N-(2,4-dimethoxybenzyl)-5-iodo-N-(thiazol-2-yl)pyridine-2-sulfonamide

(2,4-Dimethoxy-benzyl)-thiazol-2-yl-amine (0.453 g, 1.81 mmol) was dissolved in Tetrahydrofuran (5 mL, 70 mmol) and cooled in an ice bath. 1.0 M of Lithium hexamethyldisilazide in Tetrahydrofuran (2.0 mL) was added dropwise to the reaction. After addition was complete, the reaction mixture was warmed to ambient temperature. After 30 min, the reaction was cooled to at 0° C. and a solution of 5-Iodo-pyridine-2-sulfonyl chloride (0.50 g, 1.6 mmol) in Tetrahydrofuran (4 mL, 50 mmol) was added dropwise. The reaction mixture was stirred 4 h then quenched with saturated aqueous ammonium chloride. The reaction mixture was concentrated in vacuo. The residue was taken up in ethyl acetate and additional saturated aqueous ammonium chloride was added. The layers were separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered through celite, and concentrated in vacuo. The residue was purified on the ISCO twice (hexanes to ethyl acetate) to afford the product as a yellow solid.

1. temperaturecooled in an ice bath
2. additionAfter addition
3. temperaturethe reaction was cooled to at 0° C.
4. customthen quenched with saturated aqueous ammonium chloride
5. concentrationThe reaction mixture was concentrated in vacuo
6. additionadditional saturated aqueous ammonium chloride was added
7. customThe layers were separated
8. extractionthe aqueous layer was extracted with ethyl acetate
9. washThe combined organic layers were washed with brine
10. dry with materialdried over sodium sulfate
11. filtrationfiltered through celite
12. concentrationconcentrated in vacuo
13. customThe residue was purified on the ISCO twice (hexanes to ethyl acetate)

ORD record

ord-a6469b1d0b7941f0965c1f296f8df01f

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08124610B2