反应详情

4-(3-Aminopropyl)-piperidine-1-carboxylic acid tert-butyl ester (0.72 g, 3.0 mmol) is added to a stirred suspension of 2-(2,5-dichloropyrimidin-4-yl)-benzo[b]thiophene-6-carboxylic acid methylamide (0.40 g, 1.2 mmol) and diisopropylethylamine (0.38 g, 3.0 mmol) in anhydrous 1,4-dioxane (15 mL) at room temperature under nitrogen. The resultant mixture is heated in an oil bath at 90° C. for 12 hours. At room temperature, the mixture is concentrated and the resultant solid is washed with diethyl ether (20 mL) to give a yellow solid. The solid is suspended in dichloromethane (5 mL), followed by the successive addition of triethylsilane (0.7 mL) and TFA (4 mL). The resultant yellow solution is stirred for 2 hours. After concentration to dryness, the crude product is dissolved in MeOH (20 mL)/dichloromethane (10 mL) and the solution is treated in portions with 2N LiOH (4.2 mL) to form a suspension. After concentration and subsequent chromatography on silica gel, eluting with 2.0 M NH3/MeOH in dichloromethane 0-10%, the title compound is obtained as a yellow solid (0.26 g, yield 49%). ES+(m/z) 444 (35Cl) and 446 (37Cl) [M+H].

1. concentrationAt room temperature, the mixture is concentrated
2. washthe resultant solid is washed with diethyl ether (20 mL)
3. customto give a yellow solid
4. concentrationAfter concentration to dryness
5. dissolutionthe crude product is dissolved in MeOH (20 mL)/dichloromethane (10 mL)
6. additionthe solution is treated in portions with 2N LiOH (4.2 mL)
7. customto form a suspension
8. concentrationAfter concentration and subsequent chromatography on silica gel
9. washeluting with 2.0 M NH3/MeOH in dichloromethane 0-10%