Diisopropylethylamine → 3-tert-butoxycarbonyl-7-chloro-6-{5-[2-(cyclopropylmethyl-amino)-thiazol-4-yl]-pyridin-2-ylthiomethyl}-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-tert-butoxycarbonyl-7-chloro-6-mercaptomethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.078 g, 0.239 mmol) in anhydrous dioxane (1.1 mL), add N-[4-(6-bromo-pyridin-3-yl)-thiazol-2-yl]-cyclopropylmethylamine (0.067 g, 0.218 mmol), tris(dibenzylideneacetone)dipalladium(0) (5 mg, 0.0055 mmol), Xantphos (6.3 mg, 0.011 mmol) and diisopropylethylamine (0.076 mL, 0.44 mmol) at room temperature. Purge the reaction mixture with nitrogen and heat the mixture at 100° C. overnight. Cool the reaction mixture to room temperature. Dilute with DCM (50 mL) and filter through Celite®. Concentrate the filtrate in vacuo. Dissolve the residue in DCM, load the solution on to a RediSep® column (40 g) and purify the crude mixture by preparative liquid chromatography (0:100 to 25:75 EtOAc/hexane over 33 min; 35 mL/min) to afford 3-tert-butoxycarbonyl-7-chloro-6-{5-[2-(cyclopropylmethyl-amino)-thiazol-4-yl]-pyridin-2-ylthiomethyl}-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.113 g, 94%) as a pale yellow foam. MS (ES+) m/z: 557.2 (M+H)+.

Provenance & Evidence