Diisopropylethylamine → {3-[5-Chloro-4-(4-cyclopropylcarbamoyl-benzo[b]thiophen-2-yl)-pyrimidin-2-ylamino]-propyl}-carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A stirred suspension of 2-(2,5-dichloropyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid cyclopropylamide (5.59 g, 15.3 mmol) in 1.4-dioxane (60 mL), (3-amino-propyl)-carbamic acid tert-butyl ester (2.70 mL, 2.69 mg, 15.5 mmol) in N,N-diisopropylethylamine (5.20 mL, 3.86 g, 29.9 mmol) is heated at 97° C. for 120 hours. The mixture is then cooled to room temperature, diluted with dichloromethane (120 mL), filtered, washed with dichloromethane (2×25 mL), and dried to provide {3-[5-chloro-4-(4-cyclopropylcarbamoyl-benzo[b]thiophen-2-yl)-pyrimidin-2-ylamino]-propyl}-carbamic acid tert-butyl ester (5.00 g, 65%). This intermediate (4.99 g, 9.94 mmol) is suspended in methanol (120 mL) and treated with 10% aqueous HCl (10 mL) and the mixture is heated at 100° C. for 24 hours. The mixture is then cooled to room temperature, quenched with 2 N NaOH (20 mL), filtered, washed with H2O (60 mL), dichloromethane (60 mL), and diethyl ether (60 mL), and dried to provide the title compound (3.99 g, 99%).

Provenance & Evidence