Hydrochloric Acid → HCID 178423538, compound

Temperature

150 °C

To a solution of 0.17 g (0.34 mmol) 4-{2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclopentyl-ethoxy}-3,5-dimethyl-benzonitrile in 4 ml o-xylene, were added 0.231 g (1.68 mmol) triethylamine hydrochloride and 0.109 g (1.68 mmol) sodium azide and the solution was heated at 150° C. (oil bath temperature) for 19.5 h. Another 0.231 g (1.68 mmol) triethylamine hydrochloride and 0.109 g (1.68 mmol) sodium azide were added and the reaction mixture was heated for an additional 4 h, then stirred for 3 days at room temperature. The reaction mixture was poured onto aqueous 1M hydrochloric acid solution, the phases were separated and the aqueous phase extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. The residue was suspended in acetonitrile, filtered and washed with acetonitrile. The obtained crude material was purified on a preparative HPLC (Zorbax column) eluting with a gradient of acetonitrile and water containing 0.5% formic acid. White solid (18%). MS (Turbo Spray): m/z=549.199 [M+H].

1. temperaturethe reaction mixture was heated for an additional 4 h
2. customthe phases were separated
3. extractionthe aqueous phase extracted three times with ethyl acetate
4. washThe combined organic layers were washed with brine
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. customevaporated
8. filtrationfiltered
9. washwashed with acetonitrile
10. customThe obtained crude material
11. customwas purified on a preparative HPLC (Zorbax column)
12. washeluting with a gradient of acetonitrile and water containing 0.5% formic acid

ORD record

ord-0bd1f5ecaf994c7d86f26b393b4af2b7

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08088930B2