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Reference of 27808-16-8, New Advances in Chemical Research in 2021. Chemo-enzymatic cascade processes are invaluable due to their ability to rapidly construct high-value products from available feedstock chemicals in a one-pot relay manner. 27808-16-8, name is 4-Methyl-1H-1,2,3-triazole, molecular formula is C3H5N3, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, below Introduce a new synthetic route.
A solution of 4-methyl-iH-i,2,3-triazole (500 mg,6.02 mmol), 2,3-dichloro-5-nitropyridine (1277.42 mg, 6.62 mmol), K2C03 (2491.22 mg, 18.05 mmol) in CH3CN (5 mE) was stirred at it for 12 h. The mixture was concentrated under reduced pressure, the crude product was purified by colunm chromatography over silica gel (petroleum ether ethyl acetate from 20:1 to 1:1). The desired fractions were collected and the solvent was concentrated under reduced pressure to afford i25a (1.1 g, 76.3%) as a yellow solid. ECMS (ESI) mlz M+i: 239.7. Zn (1491.96 mg, 22.95 mmol) was added to a solution of mixture of 3-chloro-2-(4-methyl-2H-i,2,3-tri- azol-2-yl)-5-nitropyridine and 3-chloro-2-(4-methyl-i H-i, 2,3-triazol-i-yl)-5-nitropyridine, i25a (1.1 g, 2.30 mmol) in aqNH4C1 (30 mE) and H20 (30 mE). The mixture was stirred at it for 16 h. To the suspension was added aq NaHCO3 to adjust to pH 9-10, and the mixture was filtered through a pad of diatomaceous earth. The filter cake was washed with CH2C12 (100 mEx3). The combined filtrates were washed with brine (200 mE), dried over MgSO4 and concentrated under reduced pressure to afford mixture of 5-chloro-6-(4-methyl-2H- 1 ,2,3-triazol-2-yl)pyridin-3-amine and 5-chloro-6-(4-methyl-i H-i ,2,3-triazol- 1 -yl)pyriF din-3-amine, 125b (1 g) as a brown solid, used directly for the next step. LCMS (ESI) mlz M+H: 209.7 P0C13 (182.86 mg, 1.19 mmol) was added to a solution of 125b (300 mg, 0.72 mmol), 1-(quinolin-5-yl)-5- (trifluoromethyl)-1 H-pyrazole-4-carboxylic acid (183.19 mg, 0.60 mmol), pyridine (117.91 mg 1.49 mmol) in CH2C12 (10 mE). The mixture was stirred at it for 2h, 50 mE H20 and 50 mE CH2C12 were added to the mixture. The organic layer was washed with brine (50 mE), dried over MgSO4 and concentrated under reduced pressure to afford the crude product, which was purified by preparative HPEC (35% to 65% (v/v) CH3CN and H20 with 0.05% HC1) and lyophilized to dryness to afford the title compound (208 mg 69.8% yield) as a white solid. ECMS (ESI) mlz M+1: 499.0. ?H NMR (400 MHz, DMSO-d5) oe ppm 11.45 (s, 1H), 9.06 (t, J=2.54 Hz, 1H), 8.89 (s, 1H), 8.60-8.75 (m, 2H), 8.33 (d, J=8.38 Hz, 1H), 7.88-8.03 (m, 3H), 7.68 (d, J=2.65 Hz, 2H), 2.34 (s, 3H).
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Reference:
Patent; Janssen Biotech, Inc.; Lu, Tianbao; Allison, Brett Douglas; Barbay, Joseph Kent; Connolly, Peter J.; Cummings, Maxwell David; Diels, Gaston; Edwards, James Patrick; Kreutter, Kevin D.; Philippar, Ulrike; Shen, Fang; Thuring, Johannes Wilhelmus John Fitzgerald; Wu, Tongfei; (412 pag.)US2018/170909; (2018); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics