1,4-Dioxane → HCID 86687588, compound

Participants

Reaction Steps

To a microwave vial charged with (2-methoxy-4-(trifluoromethyl)phenyl)boronic acid (35.6 mg, 0.162 mmol), 4-chloro-6-methoxy-N-(4-methoxybenzyl)-N-(thiazol-2-yl)quinoline-7-sulfonamide (70 mg, 0.147 mmol), potassium phosphate tribasic (36.5 μl, 0.441 mmol) and 1,1-bis[(di-t-butyl-p-methylaminophenyl]palladium(ii) chloride (10.41 mg, 0.015 mmol) was added Dioxane (590 μl) and Water (197 μl). The mixture was irradiated at 100° C. for 30 mins affording conversion to desired product according to LC-MS. The mixture was dried under reduced pressure. To the crude oil was added DCM (0.9 ml) and TFA (0.3 ml) was added at room temperature. After 1 hr of stirring LC-MS indicated complete PMB cleavage. The mixture was dried under reduced pressure and purified with a 25 g (15 μm spherical silica) column ramping EtOAc in heptane (0-100%, 10% DCM throughout) providing product, obtained as a film. The material was lyophilized from MeOH/H2O providing 6-methoxy-4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)quinoline-7-sulfonamide (53 mg, 0.107 mmol, 72.7% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.62 (s, 3H) 3.80 (s, 3H) 6.83 (s, 1H) 6.88 (d, J=4.60 Hz, 1H) 7.28 (d, J=4.60 Hz, 1H) 7.47-7.54 (m, 3H) 7.57 (d, J=7.63 Hz, 1H) 8.52 (s, 1H) 8.91 (d, J=4.40 Hz, 1H) 12.80 (br. s., 1H). m/z (ESI) 496.2 (M+H)+.

Provenance & Evidence