tert-Butanol → 4-[4-(2-Fluoro-pyridin-4-ylmethoxy)-[1,2,5]thiadiazol-3-yl]-piperazine-1-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)-amide

To a solution of 4-(4-chloro-[1,2,5]thiadiazol-3-yl)-piperazine-1-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)-amide (117.7 mg, 0.265 mmol, prepared in Example 10b) and 1M solution of potassium tert-butoxide in tert-butanol (0.75 mL, 0.75 mmol) was added 2-Fluoro-4-pyridinemethanol (65.6 mg, 0.516 mmol, prepared in Example 15a). The resulting suspension was stirred at room temperature for 2 h. The crude reaction mixture was diluted with methanol and purified by preparative HPLC (50 mM NH4OAc(aq), Acetonitrile system). The pure fractions were combined and the acetonitrile was removed in vacuo. The remaining aqueous solution was made basic with NaHCO3 and the free based product was extracted into EtOAc. The organic phase was concentrated in vacuo, and the solids were re-dissolved in acetonitrile/water and lyophilized to obtain pure product 4-[4-(2-Fluoro-pyridin-4-ylmethoxy)-[1,2,5]thiadiazol-3-yl]-piperazine-1-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)-amide. (19.0 mg, 13.5% yield). 1H NMR (CDCl3) 8.26 (d, 1H), 7.88 (s, 2H), 7.53 (s, 1H), 7.22 (d, 1H), 6.98 (s, 1H), 6.88 (s, 1H), 5.53 (s, 2H), 3.73-3.50 (m, 8H) ppm.

1. customThe crude reaction mixture
2. custompurified by preparative HPLC (50 mM NH4OAc(aq), Acetonitrile system)
3. customthe acetonitrile was removed in vacuo
4. extractionwas extracted into EtOAc
5. concentrationThe organic phase was concentrated in vacuo
6. dissolutionthe solids were re-dissolved in acetonitrile/water

ORD 기록

ord-7f78d7f2ade84880a72f658488bd7056

출처 데이터셋

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08013156B2