反应详情

N-(5-(((3S)-3-methyl-4-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-1-piperazinyl)sulfonyl)-1,3,4-thiadiazol-2-yl)acetamide was synthesized following the procedure reported for Example 30, replacing 3-furansulfonyl chloride with 5-(acetylamino)-1,3,4-thiadiazole-2-sulfonyl chloride (Eur. J. Med. Chem., 2006, 41, 918). A solution of N-(5-((3S)-3-methyl-4-(4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl)piperazin-1-ylsulfonyl)-1,3,4-thiadiazol-2-yl)acetamide (85 mg, 0.172 mmol) in aqueous 5N HCl (5 mL, 5.00 mmol) was heated to 100° C. for 3 h. The mixture was diluted with water (20 mL) and extracted with EtOAc (3×100 mL). The organic layer was separated, dried (Na2SO4), filtered and concentrated. The crude material was purified by column chromatography (12 g of silica, 0 to 100% (10% [2M ammonia in methanol]/CH2Cl2) in CH2Cl2) to yield 2-(4-((2S)-4-((5-amino-1,3,4-thiadiazol-2-yl)sulfonyl)-2-methyl-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol (20 mg) as a mixture of 2 isomers.

1. extractionextracted with EtOAc (3×100 mL)
2. customThe organic layer was separated
3. dry with materialdried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated
6. customThe crude material was purified by column chromatography (12 g of silica, 0 to 100% (10% [2M ammonia in methanol]/CH2Cl2) in CH2Cl2)