反应详情

A solution of 3,5-dichloro-1H-pyrazol-1-acetic acid (70 mg, 0.36 mmol) (i.e. the product of Example 12, Step F) in dichloromethane (1 mL) and a catalytic amount of N,N-dimethylformamide (1 drop) was treated with oxalyl chloride (0.1 mL, 1.1 mmol) and stirred at ambient temperature for 20 minutes. The reaction mixture was concentrated under reduced pressure and re-dissolved in dichloromethane (1 mL). The reaction mixture was added to a stirred suspension of N-methyl-2-(4-piperidinyl)-N-[(1R)-1,2,3,4-tetrahydro-1-naphthalenyl]-4-thiazolecarboxamide monohydrochloride (i.e. the product of Example 6, Step C) (100 mg, 0.26 mmol), triethylamine (0.1 mL, 0.72 mmol), and potassium carbonate (150 mg, 1 mmol) in dichloromethane (2 mL). The reaction mixture was then heated to reflux for 2 h, and then cooled to ambient temperature. The resulting suspension was diluted with dichloromethane (10 mL), filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography using 50-100% ethyl acetate in hexanes as eluant to give 80 mg of the title product, a compound of the present invention as an oil.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. dissolutionre-dissolved in dichloromethane (1 mL)
3. temperatureThe reaction mixture was then heated
4. temperatureto reflux for 2 h
5. temperaturecooled to ambient temperature
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe crude product was purified by silica gel chromatography