Lithium → 3-Fluoro-4-[(1,2,4-thiadiazol-5-ylamino)sulfonyl]benzoic acid

Temperatur

-78 °C

N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine (Preparation 26, 500 mg, 2.1 mmol, 1.0 eq) was dissolved in THF (10 ml) and cooled to −78° C. 1,1,1,3,3,3-Hexanemethyldisilazane lithium salt (LiHMDS, 1M in THF, 4.2 ml, 4.19 mmol, 2.0 eq) was added dropwise and the reaction mixture stirred for a further 10 minutes. A solution of 4-(chlorosulfonyl)-3-fluorobenzoic acid (Preparation 9, 500 mg, 2.1 mmol, 1 eq) in THF (3 ml) was added dropwise and the reaction mixture stirred at −78° C. for 1 hour then at room temperature for 18 hours. The reaction mixture was diluted with brine, extracted into ethyl acetate, dried over sodium sulphate, filtered and evaporated in vacuo. The crude material was passed through a SCX cartridge to remove remaining amine. The material was redissolved in 4M HCl in dioxane and stirred at room temperature for 2 hours. The resulting precipitate was collected by filtration and washed with diethylether to yield the title compound (100 mg, 0.33 mmol, 16%).

1. stirringthe reaction mixture stirred at −78° C. for 1 hour
2. waitat room temperature for 18 hours
3. extractionextracted into ethyl acetate
4. dry with materialdried over sodium sulphate
5. filtrationfiltered
6. customevaporated in vacuo
7. customto remove
8. dissolutionThe material was redissolved in 4M HCl in dioxane
9. stirringstirred at room temperature for 2 hours
10. filtrationThe resulting precipitate was collected by filtration
11. washwashed with diethylether

ORD-Eintrag

ord-5d150023172042c38609c17a69f9decb

Quelldatensatz

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08357711B2