Ro-N-heterocycles in great to highdx.doi.org/10.1021/jo500365h | J. Org. Chem. 2014, 79, 4167-The Journal of Organic ChemistryNoteFigure three. (Left) Proposed mechanism on the CuI-catalyzed formation of aminoynone, two, and 1,2-dihydro-2-aminoethynylquinoline, 16, and (appropriate) conversion with the ynamide to two and 16 vs time.yields. The easy access to these synthetically versatile ynamide derivatives is expected to prove invaluable to medicinal chemistry and all-natural item synthesismercially accessible reagents and solvents were made use of without further purification. Anhydrous solvents had been used as bought and not dried any additional. NMR spectra had been obtained at 400 MHz (1H NMR) and one hundred MHz (13C NMR) in deuterated chloroform. Chemical shifts are reported in ppm relative to TMS. Common Procedure for the Copper-Catalyzed Ynamide Addition to Acyl Chlorides. Copper iodide (2.3 mg, 12 mol), N-ethynyl-N-phenyl-4-tolylsulfonamide (32.five mg, 0.12 mmol), and N,N-diisopropylethylamine (31.0 mg, 0.24 mmol) have been dissolved in chloroform (0.15 mL) below nitrogen. Soon after 30 min an acyl chloride (0.18 mmol) was added, and also the mixture was stirred till completion as determined by TLC. Solvents were evaporated beneath a stream of nitrogen, plus the crude residue was purified by flash chromatography on silica gel (particle size 40-63 m) as described beneath. Common Process for the Copper-Catalyzed Ynamide Addition to Pyridines and Quinolines. The ynamide (54.2 mg, 0.20 mmol), CuI (three.8 mg, 0.02 mmol), and N,N-diisopropylethylamine (70 L, 0.40 mmol) have been dissolved in 1 mL of anhydrous dichloromethane.1258874-29-1 uses Then, a solution with the N-heterocycle (0.1,4-Dichloro-9,10-anthraquinone structure 24 mmol) and ethyl chloroformate (38 L, 0.PMID:24883330 40 mmol) in 1 mL of anhydrous dichloromethane was added. The mixture was stirred under nitrogen till the reaction was completed based on NMR and TLC evaluation. Solvents have been then removed, along with the crude residue was directly loaded onto a silica gel column (particle size 32-63 m) and purified by flash chromatography as described beneath unless stated otherwise. N-(3-Phenyl-3-oxoprop-1-ynyl)-N-phenyl-4-tolylsulfonamide, two. The reaction with benzoyl chloride (25.1 mg, 0.18 mmol) and also the ynamide (32.five mg, 0.12 mmol) was performed at 30 for 22 h. The concentrated crude residue was purified by column chromatography (two:1 dichloromethane/hexanes) to offer 40.five mg (0.108 mmol, 90 ) of a white strong. 1H NMR (400 MHz): eight.19 (d, J = six.9 Hz, 2H), 7.67-7.57 (m, 3H), 7.52 (dd, J = 8.four Hz, six.9 Hz, 2H), 7.41-7.34 (m, 3H), 7.30-7.22 (m, 4H), 2.42 (s, 3H). 13C NMR (100 MHz): 176.8, 145.9, 137.2, 136.9, 133.six, 132.9, 129.9, 129.5, 129.17, 129.15, 128.six, 128.1, 126.5, 90.1, 74.9, 21.six. Anal. Calcd For C22H17NO3S: C, 70.38; H, 4.56; N, three.73. Identified: C, 70.51; H, 4.73; N, 3.86. Mp 139-140 . N-(3-(2-Chlorophenyl)-3-oxoprop-1-ynyl)-N-phenyl-4-tolylsulfonamide, three. The reaction with 2-chlorobenzoyl chloride (32.six mg, 0.186 mmol) and the ynamide (32.5 mg, 0.12 mmol) was performed at 30 for 18 h. The concentrated crude residue wasEXPERIMENTAL SECTIONpurified by column chromatography (five:two dichloromethane/hexanes) to provide 45 mg (0.11 mmol, 92 ) of a white strong. 1H NMR (400 MHz): eight.06 (d, J = 7.six Hz, 1H), 7.60 (d, J = eight.3 Hz, 2H), 7.45 (d, J = 3.six Hz, 2H), 7.45-7.31 (m, 4H), 7.31-7.21 (m, 4H), 2.43 (s, 3H). 13C NMR (one hundred MHz): 175.3, 145.9, 137.1, 135.four, 133.1, 133.0, 132.9, 132.4, 131.four, 129.9, 129.4, 129.two, 128.two, 126.eight, 126.five, 91.0, 76.three, 21.7. Anal. Calcd For C22H16ClNO3S: C, 64.47; H, 3.93; N, three.42. Located: C, 6.