反应详情

温度

97 °C

A stirred mixture of 2-(2-chloro-5-methylpyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid [bis-(4-methoxyphenyl)-methyl]-amide (1.14 g, 2.15 mmol), 4-(3-aminopropyl)-piperidine-1-carboxylic acid tert-butyl ester (1.04 g, 4.30 mmol) and diisopropylethylamine (1.12 mL, 6.45 mmol) in 1,4-dioxane (10 mL) is heated at 97° C. under a nitrogen atmosphere for 3 days. After concentration and subsequent chromatography on silica gel, eluting with MeOH in dichloromethane 0-2%, the desired product is obtained as a solid. The solid is suspended in dichloromethane (20 mL), followed by the successive addition of triethylsilane (1.5 mL) and TFA (5 mL). The resultant yellow solution is stirred for 2 hours. After concentration the solid is dissolved with stirring in MeOH (30 mL) and dichloromethane (30 mL) and the solution is treated in portions with 1.0 N LiOH (15 mL) to form a suspension. The suspension is concentrated at 45° C. under atmospheric pressure for 30 minutes, then methanol and dichloromethane are evaporated off in vacuo. The suspension is filtered and the yellow solid is dried under vacuum at 45° C. to provide the title compound (0.890 g, 100% yield). ES+(m/z) 410 [M+H].

1. concentrationAfter concentration and subsequent chromatography on silica gel
2. washeluting with MeOH in dichloromethane 0-2%