Triethylamine → 2-[5-Bromo-3-(trifluoromethyl)-1h-pyrazol-1-yl]-1-[4-[4-(4,5-dihydro-5-phenyl-3-isoxazolyl)-2-thiazolyl]-1-piperidinyl]ethanone

To a solution of 5-bromo-3-(trifluoromethyl)-1H-pyrazole-1-acetic acid (i.e. the product of Example 11, Step D) (0.12 g, 0.61 mmol) in dichloromethane (5 mL) was added N,N-dimethylformamide (1 drop) followed by oxalyl chloride (0.25 mL, 2.86 mmol). The reaction mixture was stirred at room temperature for 1 h and then concentrated under reduced pressure. The residue containing crude acid chloride was taken up in dichloromethane (5 mL), and the solution was added dropwise to a mixture of 4-[4-(4,5-dihydro-5-phenyl-3-isoxazolyl)-2-thiazolyl]-1-piperidine hydrochloride (i.e. the intermediate of Example 10, Step F) (0.15 g, 0.43 mmol) and triethylamine (0.25 mL, 1.8 mmol) in dichloromethane (5 mL) at 0° C. The reaction mixture was allowed to warm to room temperature and then stirred overnight at room temperature. The mixture was then partitioned between 1.0 N aqueous hydrochloric acid solution and dichloromethane. The organic layer was washed with water, dried (MgSO4), concentrated under reduced pressure, and purified by medium-pressure liquid chromatography using ethyl acetate in hexanes as eluant to give 90 mg of the title product as an amorphous solid.

1. concentrationconcentrated under reduced pressure
2. additionThe residue containing crude acid chloride
3. temperatureto warm to room temperature
4. stirringstirred overnight at room temperature
5. customThe mixture was then partitioned between 1.0 N aqueous hydrochloric acid solution and dichloromethane
6. washThe organic layer was washed with water
7. dry with materialdried (MgSO4)
8. concentrationconcentrated under reduced pressure
9. custompurified by medium-pressure liquid chromatography

ORD record

ord-3144d2aa8a1b4235a9f9aae51e5d79df

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08449898B2