With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.349-49-5,4-(Trifluoromethyl)thiazol-2-amine,as a common compound, the synthetic route is as follows.
(Example 48) 4-Hydroxy-4-(trifluoromethyl)-3-{1-[4-(trifluoromethyl)1,3-thiazol-2-yl]piperidin-4-yl}-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (hereinafter, referred to as compound 48-a)[0476] Copper(II) chloride (2.90 g, 21.57 mmol) was added to a solution of 2-amino-4-(trifluoromethyl)thiazole (3.05 g, 18.14 mmol) in acetonitrile (80 mL), then isoamyl nitrite (3.60 mL, 27.04 mmol) was added dropwise thereto at 0¡ãC, and the mixture was stirred at room temperature for 1 hour and at 50¡ãC for 2 hours. Then, the solvent in the reaction solution was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography [elute: hexane/ethyl acetate = 100/0 – 70/30 (gradient)] to obtain an oil (1.12 g)._: [0478] 4-Hydroxy-3-(piperidin-4-yl)-4-(trifluoromethyl)-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one (62 mg, 0.18 mmol) produced in Reference Example 60 and N,N-diisopropylethylamine (40 muL, 0.24 mmol) were added to a solution of the obtained oil (55 mg) in dimethyl sulfoxide (2 mL), and the mixture was stirred at room temperature for 5 hours and further at 0¡ãC for 2 hours and 30 minutes. The reaction solution was diluted with ethyl acetate, washed with water and brine, and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography [elute: hexane/ethyl acetate = 70/30 – 10/90 (gradient)] to obtain the title compound 48-a (6 mg, yield: 6percent) and compound 48-b (18 mg, yield: 16percent). Compound 48-a 1H-NMR (400 MHz, DMSO-d6) delta: 12.29 (1H, s), 10.53 (1H, s), 7.54 (1H, s), 6.79 (1H, s), 4.05-3.96 (2H, m), 3.40-3.20 (1H, m), 3.14 (2H, t, J = 12 Hz), 2.90 (1H, d, J = 16 Hz), 2.73 (1H, d, J = 16 Hz), 1.94-1.74 (4H, m); MS (ESI) m/z: 456 (M+H)+.Compound 48-b 1H-NMR (400 MHz, DMSO-d6) delta: 12.27 (1H, s), 10.54 (1H, s), 8.61 (1H, s), 6.80 (9H, s), 4.10 (2H, d, J = 13 Hz), 3.33-3.18 (3H, m), 2.90 (1H, d, J = 16 Hz), 2.73 (1H, d, J = 16 Hz), 1.99-1.74 (4H, m); MS (ESI) m/z: 607 (M+H)+., 349-49-5
As the paragraph descriping shows that 349-49-5 is playing an increasingly important role.
Reference£º
Patent; Daiichi Sankyo Company, Limited; KOBAYASHI, Hideki; OHKAWA, Nobuyuki; TAKANO, Daisuke; KUBOTA, Hideki; ONODA, Toshio; KANEKO, Toshio; ARAI, Masami; TERASAKA, Naoki; EP2862861; (2015); A1;,
Thiazole | C3H3NS – PubChem
Thiazole | chemical compound | Britannica