Diisopropylethylamine → 4-{2-[5-Bromo-4-(4-cyclopropylcarbamoylbenzo[b]thiophen-2-yl)-pyrimidin-2-ylamino]-ethyl}-4-methylpiperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A stirred mixture of 2-(5-bromo-2-chloropyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid cyclopropylamide (400 mg, 0.979 mmol), 4-(2-aminoethyl)-4-methyl-piperidine-1-carboxylic acid tert-butyl ester (474 mg, 1.96 mmol) and diisopropylethylamine (253 mg, 1.96 mmol) in 1,4-dioxane (10 mL) is heated at 90° C. under nitrogen for 18 hours. At room temperature the mixture is concentrated and the crude product is chromatographed on silica gel, eluting with 3% 2 M NH3/MeOH in dichloromethane, to give 602 mg of 4-{2-[5-bromo-4-(4-cyclopropylcarbamoylbenzo[b]thiophen-2-yl)-pyrimidin-2-ylamino]-ethyl}-4-methylpiperidine-1-carboxylic acid tert-butyl ester. It is then subject to deprotection by dissolving the material (132 mg, 0.220 mmol) in MeOH (10 mL) and dichloromethane (5 mL) and bubbling anhydrous HCl gas for 5 minutes. The hot, yellow solution is allowed to sit at room temperature for 1.5 hours, then concentrated to give the title compound as a yellow solid (126 mg, 100% yield). ES+(m/z) 514 (79Br) and 516 (81Br) [M(free base)+H].

Provenance & Evidence