Triethylamine → 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-(4,5-dihydro-3,5-dimethyl-1H-pyrazol-1-yl]ethanone

A mixture of 4,5-dihydro-3,5-dimethyl-1H-pyrazole-1-acetic acid (i.e. the product of Step B) (0.10 g, 0.64 mmol), 4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]piperidine (i.e. the product of Example 1, Step D) (175 mg, 0.5 mmol), N3-(ethylcarbodimidoyl)-N1,N1-dimethyl-1,3-propanediamine hydrochloride (191 mg, 1.0 mmol), 1-hydroxybenzotriazole (5 mg, 0.037 mmol) and triethylamine (0.14 mL, 1.0 mmol) in dichloromethane (4 mL) was stirred at room temperature. After 6 h, more N3-(ethylcarbodimidoyl)-N1,N1-dimethyl-1,3-propanediamine hydrochloride (191 mg, 1.0 mmol) and triethylamine (0.14 mL, 1.0 mmol) were added to the reaction mixture. After 3 days, the reaction mixture was diluted with dichloromethane, washed with saturated aqueous ammonium chloride solution and concentrated under reduced pressure. The resulting residue was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes, and then 20% methanol in ethyl acetate as eluant) to provide the title compound, a compound of the present invention, as a tan solid (124 mg).

1. waitAfter 3 days
2. washwashed with saturated aqueous ammonium chloride solution
3. concentrationconcentrated under reduced pressure
4. customThe resulting residue was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes

ORDレコード

ord-5efce5baf7f1430ca253fe4b055124b6

出典データセット

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08618137B2