Talytic ynamide addition towards the activated quinoline ring showed quantitative conversion to 1,2-dihydro-2-aminoethynylquinoline, 16, inside

Talytic ynamide addition towards the activated quinoline ring showed quantitative conversion to 1,2-dihydro-2-aminoethynylquinoline, 16, inside 20 min, whereas no item was isolated when the reaction was carried out within the absence of CuI for two.five h. In conclusion, we’ve got developed the initial catalytic addition of a readily available ynesulfonamide to aliphatic and aromatic acyl chlorides. A slightly modified Procedure has been effectively used for regioselective 1,2-addition of ynamides to pyridines and quinolines. Both reactions take place under mild situations and provide unprecedented access to various 3aminoynones and 1,2-dihydro-N-heterocycles in excellent to highdx.doi.org/10.1021/jo500365h | J. Org. Chem. 2014, 79, 4167-The Journal of Organic ChemistryNoteFigure 3. (Left) Proposed mechanism of the CuI-catalyzed formation of aminoynone, two, and 1,2-dihydro-2-aminoethynylquinoline, 16, and (right) conversion from the ynamide to 2 and 16 vs time.yields. The convenient access to these synthetically versatile ynamide derivatives is anticipated to prove invaluable to medicinal chemistry and organic solution synthesismercially out there reagents and TXB2 web Solvents were employed with no additional purification. Anhydrous solvents were utilised as bought and not dried any additional. NMR spectra have 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. Basic Procedure for the Copper-Catalyzed Ynamide Addition to Acyl Chlorides. Copper iodide (two.3 mg, 12 mol), N-ethynyl-N-phenyl-4-tolylsulfonamide (32.5 mg, 0.12 mmol), and N,N-diisopropylethylamine (31.0 mg, 0.24 mmol) have been dissolved in chloroform (0.15 mL) beneath nitrogen. Following 30 min an acyl chloride (0.18 mmol) was added, along with the mixture was stirred till completion as determined by TLC. Solvents were evaporated under a stream of nitrogen, along with the crude residue was SIRT2 medchemexpress purified by flash chromatography on silica gel (particle size 40-63 m) as described below. Common Procedure for the Copper-Catalyzed Ynamide Addition to Pyridines and Quinolines. The ynamide (54.2 mg, 0.20 mmol), CuI (3.8 mg, 0.02 mmol), and N,N-diisopropylethylamine (70 L, 0.40 mmol) have been dissolved in 1 mL of anhydrous dichloromethane. Then, a answer of your N-heterocycle (0.24 mmol) and ethyl chloroformate (38 L, 0.40 mmol) in 1 mL of anhydrous dichloromethane was added. The mixture was stirred below nitrogen till the reaction was completed based on NMR and TLC evaluation. Solvents have been then removed, plus the crude residue was directly loaded onto a silica gel column (particle size 32-63 m) and purified by flash chromatography as described under unless stated otherwise. N-(3-Phenyl-3-oxoprop-1-ynyl)-N-phenyl-4-tolylsulfonamide, 2. The reaction with benzoyl chloride (25.1 mg, 0.18 mmol) and the ynamide (32.5 mg, 0.12 mmol) was performed at 30 for 22 h. The concentrated crude residue was purified by column chromatography (2:1 dichloromethane/hexanes) to give 40.5 mg (0.108 mmol, 90 ) of a white strong. 1H NMR (400 MHz): 8.19 (d, J = 6.9 Hz, 2H), 7.67-7.57 (m, 3H), 7.52 (dd, J = 8.4 Hz, six.9 Hz, 2H), 7.41-7.34 (m, 3H), 7.30-7.22 (m, 4H), two.42 (s, 3H). 13C NMR (100 MHz): 176.8, 145.9, 137.2, 136.9, 133.6, 132.9, 129.9, 129.five, 129.17, 129.15, 128.six, 128.1, 126.5, 90.1, 74.9, 21.6. Anal. Calcd For C22H17NO3S: C, 70.38; H, four.56; N, three.73. Located: C, 70.51; H, 4.73; N, three.86. Mp 139-140 . N-(3-(2-Chlorophenyl)-3-oxoprop-1-ynyl)-N-phenyl-4-tolylsulfonamide, three. The reaction with 2-chloro.