Diisopropylethylamine → 1-(4-(2-(3-aminopyridin-4-yl)ethoxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea

Participants

Reaction Steps

A solution of 3-tert-butyl-5-isocyanato-1-p-tolyl-1H-pyrazole (19) (530 mg, 2.076 mmol) in THF (2.0 mL) was added to a solution of 4-(2-(4-aminonaphthalen-1-yloxy)ethyl)pyridin-3-amine (18) (580 mg, 2.076 mmol) and DIPEA (1085 μl, 6.23 mmol) in THF (10 mL) and MeCN (1.0 mL) the reaction mixture stirred at RT overnight. The mixture was poured into brine (25 mL) and extracted with EtOAc (2×25 mL), dried, filtered and the solvent removed in vacuo. The product was pre-adsorbed onto hyflo (10 g), and purified by reverse phase column chromatography (40 g, C18 (from Silicycle), acetonitrile/water, 0 to 100%) and the product fractions concentrated in vacuo to give 1-(4-(2-(3-aminopyridin-4-yl)ethoxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl) urea (Intermediate E) as an off white solid (410 mg, 36%). m/z 535 (M+H)+ (ES+).

Provenance & Evidence