In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 7170-01-6, name is 3-Methyl-1H-1,2,4-triazole belongs to Triazoles compound, it is a common compound, a new synthetic route is introduced below. 7170-01-6
2,3-Dichloro-5-nitropyridine (2 g, 10.36 mmol), 3-methyl-1H-1,2,4-triazole (1.722 g, 20.73 mmol) and Cs2CO3 (6.798 g, 20.73 mmol) were added to DMF (30 mL) and the reaction was stirred at rt for 12 h. The reaction mixture was quenched with water (200 mL). The mixture was extracted with ethyl acetate (100 mL*3). The organic layer was dried over Na2SO4, filtered, and the filtrate concentrated under reduced pressure. The crude residue was purified by flash column chromatography over silica gel (petroleum ether/ethyl acetate from 100:0 to 50:50) to afford a mixture of compounds 20a and 20a-1 (780 mg, 31%) as a white solid. A mixture of 3-chloro-2-(3-methyl-i H-i ,2,4-tri-azol- i -yl)-5-nitropyridine, 20a and 3-chloro-2-(5-methyl-i H-i ,2,4-triazol-i -yl)-5-nitropyridine, 20a- i (780 mg, i .63mmol) was dissolved in MeOH (20 mE), and Zn (0) (i.058g, i 6.28 mmol) and aqueous NH4C1 (20 mE) were added.The reaction mixture was stirred at rt for i 6 h. The reactionmixture was filtered though a pad of diatomaceous earth andthe pad washed with ethyl acetate (20 mEx3). Water (50 mE)was added and the organic layer was separated, dried overNa2SO4, filtered and the filtrate was concentrated to drynessto give a crude mixture of compounds 20b and 20b- i (400mg, 59%) as a yellow solid. ?H NMR (400 MHz, METHANOE-d 4) oe ppm 2.43 (s, 3H), 2.85 (d, J=0.66 Hz, iH), 2.99(s, iH), 7.2i-7.23 (m, iH), 7.82 (d, J=2.65 Hz, iH), 7.86(dd, J=4.85, 2.43 Hz, iH), 8.02 (s, iH), 8.6i-8.65 (m, iH),8.63 (s, iH).10965] A mixture of compounds 5-chloro-6-(3-methyl-1 H-i ,2,4-triazol- i -yl)pyridin-3-amine, 20b and 5-chioro-6- (5-methyl-i H-i ,2,4-triazol- i -yl)pyridin-3-amine, 20b- i (iOO mg, 0.3i mmol), i-(isoquinolin-4-yl)-5-(trifluorom- ethyl)-iH-pyrazole-4-carboxylic acid, 4c (263.0 mg, 0.63 mmol), and pyridine (62.0 mg, 0.78 mmol) were dissolved in dichioromethane (iO mE), and P0C13 (96.2 mg, 0.63 mmol) was added. The mixture was stirred at rt for 2.5 h. Sat. aqueous NH4C1 (20 mE) was added and the mixture was extracted with dichloromethane (20 mEx2). The combined organic layers were dried over Na2504, filtered, and the filtrates were concentrated under reduced pressure to afford a crude yellow oil. The crude oil was purified by reverse phase HPEC (A: water (0.05% HC1)-CAN, B: MeCN, AB:(48%/52%). The pure fractions were concentrated under reduced pressure and lyophilized to dryness to afford a mixture of compounds 53 and 54 (90 mg). The mixture was separated by Supercritical Fluid Chromatography (0.i% NH3H2O: MEOH. Mobile phase: A: CO2 B: 0.i% NH3H2O:MEOH; AB 75/25).10966] Cpd 53:10967] N-(5-chloro-6-(3-methyl- iH- i ,2,4-triazol-i -yl)pyridin-3-yl)- i -(isoquinolin-4-yl)-5-(trifluoromethyl)- iHpyrazole-4-carboxamide, (37.8 mg, 24.i%) as a white solid. ECMS (ESI) mlz M+i: 498.9. ?H NMR (400 MHz, DMSOd 5) oe ppm 2.34-2.40 (m, 3H), 7.27-7.30 (m, iH), 7.8i-7.90 (m, iH), 7.90-7.97 (m, iH), 8.33-8.4i (m, iH), 8.66-8.72 (m, iH), 8.74-8.82 (m, 2H), 8.86-8.98 (m, 2H), 9.60 (s, iH).10968] Cpd 54:10969] N-(5-chloro-6-(5-methyl-i H-i ,2,4-triazol-i -yl)pyridin-3-yl)- i -(isoquinolin-4-yl)-5-(trifluoromethyl)- iHpyrazole-4-carboxamide (i8.4 mg, 11.7%) as a white solid.ECMS (ESI) mlz M+i: 499.0. ?H NMR (400 MHz, DMSOd 5) oe ppm 2.34-2.37 (m, 3H), 7.23-7.32 (m, iH), 7.82-7.90(m, iH), 7.9i-7.98 (m, iH), 8.06-8.i2 (m, iH), 8.33-8.4i(m, iH), 8.59-8.64 (m, iH), 8.65-8.70 (m, iH), 8.75-8.8i(m, iH), 8.85-8.90 (m, iH), 9.58-9.64 (m, iH).
The synthetic route of 7170-01-6 has been constantly updated, and we look forward to future research findings.
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