Lithium Hydroxide → Racemic 2-[5-Methyl-2-(3-piperidin-3-ylpropylamino)-pyrimidin-4-yl]-benzo[b]thiophene-4-carboxylic acid cyclopropylamide

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Reaction Conditions

Reaction Steps

A stirred mixture of 2-(2-chloro-5-methylpyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid cyclopropylamide (0.50 g, 1.5 mmol), racemic 3-(3-aminopropyl)-piperidine-1-carboxylic acid tert-butyl ester (0.88 g, 3.6 mmol) and diisopropylethylamine (0.47 g, 3.6 mmol) in 1,4-dioxane (7 mL) is heated at 90° C. under a nitrogen atmosphere for 48 hours. After concentration and subsequent chromatography on silica gel, eluting with 2 M NH3/MeOH in dichloromethane 1-10%, the intermediate is obtained as a solid. The solid is suspended in dichloromethane (3 mL), followed by the successive addition of triethylsilane (0.50 mL) and TFA (3 mL), the resultant yellow solution is stirred for 16 hours. After concentration a wet solid is obtained. It is treated with 2 N LiOH, with sonication, until pH reaches 12. The mixture is filtered and the solid is dried before it is subjected to chromatography on silica gel, eluting with 2 M NH3/MeOH in dichloromethane 10-20%, to give the title compound as a yellow solid (160 mg, 25% yield). ES+(m/z) 450 [M+H].

Provenance & Evidence