Triethylamine → 5-{2,5-Dichloro-4-[3-(3,4-dihydro-2H-quinoline-1-carbonyl)-pyridin-2-yloxy]-phenyl}-pent-4-ynoic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

To a degassed suspension of [2-(4-bromo-2,5-dichloro-phenoxy)-pyridin-3-yl]-(3,4-dihydro-2H-quinolin-1-yl)-methanone (50 mg, 0.10 mmol, 1.0 equiv; Example 165) in THF (2 mL) under Ar was added pent-4-ynoic acid methyl ester (34 mg, 0.30 mmol, 3 equiv; [CAS RN 21565-82-2]), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (1 mg, 0.001 mmol, 0.01 equiv; [CAS RN 52522-40-4]), copper(I) iodide (0.2 mg, 0.001 mmol, 0.01 equiv; [CAS RN 7681-65-4]) and triethylamine (20 mg, 28 μL, 0.20 mmol, 2.0 equiv; [CAS RN 121-44-8]). The reaction mixture was stirred at 60° C. over the weekend. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps, a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water provided 3 mg (6%) of the title compound as a light brown oil. MS (ISP): 509.1 [M+H]+.

Provenance & Evidence