Water → N-(4-chloro-2-(pyridin-3-yl)thiazol-5-yl)-N-ethyl-2-methyl-3-(methylthio)propanamide

Participants

Reaction Steps

To a dry 50 ml round bottom flask equipped with magnetic stirrer, addition funnel, and nitrogen inlet was charged 1.0 g (3.05 mmoles) of N-(4-chloro-2-(pyridin-3-yl)-1,3-thiazol-5-yl)-2-methyl-3-(methylthio)propanamide and 10 mLs of anhydrous N,N-dimethyl formamide. To the resulting solution was then added 1.1 g (3.36 mmoles) of cesium carbonate powder in one portion, followed by the dropwise addition of 0.523 g (3.36 mmoles) of iodoethane in 5 mLs of anhydrous N,N-dimethyl formamide. The heterogeneous mixture was stirred at ambient temperature for 12 hours. Analysis of an aliquot indicated incomplete reaction. An additional 100 ul of iodoethane was added and the reaction was heated at 60° C. for 3 hours, then poured into 200 mLs of water and extracted with methylene chloride (3×100 mLs). The combined organic extracts were washed with water (100 mLs), saturated aqueous sodium chloride solution (100 mLs) dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum on a rotary evaporator. The crude product was purified by silica gel flash chromatography, eluting with a gradient of 100% hexane to 100% ethyl acetate over 20 minutes to yield a yellow oil which crystallized upon standing (0.38 g, 35%): mp 80-81° C.; 1H NMR (400 MHz, CDCl3) δ 9.12 (d, J=1.9 Hz, 1H), 8.72 (dd, J=4.8, 1.4 Hz, 1H), 8.22 (ddd, J=8.0, 2.2, 1.8 Hz, 1H), 7.43 (ddd, J=8.0, 4.8, 0.6 Hz, 1H), 4.03-3.80 (m, 1H), 3.80-3.59 (m, 1H), 2.97-2.68 (m, 2H), 2.60-2.39 (m, 1H), 2.03 (s, 3H), 1.30-1.16 (m, 6H); 13C NMR (101 MHz, DMSO-d6) δ 175.66, 162.63, 151.89, 147.14, 138.19, 133.49 133.23, 128.58, 123.90, 44.81, 38.94, 37.93, 18.16, 16.83, 12.90.

Provenance & Evidence