According to the analysis of related databases, 1-Methyl-1H-1,2,3-triazole, the application of this compound in the production field has become more and more popular.
16681-65-5, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 16681-65-5 as follows.
Example 156a: (4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,4-dimethyloxazol-5-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol To a flask containing 1 -methyl- lH-1 ,2,3-triazole (200 nig, 2.41 mmol, prepared according to PCX int. AppL, 2008098104) was added Tl IF (20 mL) and the colorless solution was cooled to – 40 C. Then, -BuLi (2.5 M in hexanes, 1 ,0 mL, 2.5 mmol) was added drop wise which afforded a dark reddish-brown viscous solution. The mixture was stirred at -30 C for 35 minutes, then a homogeneous THF solution of (4-chioro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6- yl)(2,4-dimethyloxazol-5-yl)methanone (500 mg, 1.05 mmol, in 4 mL THF, Intermediate 87: step b) was introduced at -20 C. The reaction mixture became a dark brown color and was then placed in an ice-water bath and allowed to warm gradually to room temperature. After 45 minutes, the mixture was quenched with aqueous NH4C1 solution and extracted with EtOAc:THF (10:2), 4 x 50 mL. The combined organies were washed with brine, dried over Na2S04, filtered and concentrated to provide a brown oil. Chromatography on silica gel (3% MeOH-DCM increasing to 5% MeOH-DCM) to provide the title compound as a faint amber solid. MS m/e558.2 [M+H]+. H NMR (400 MHz, CDGU) delta ppm 8.15 (d, J = 2.0 Hz, 1H), 7.86 (d, J = 8.8 Hz, 1 1 1). 7.54 – 7.47 (m, 3H), 7.40 (d, ./ 8.1 Hz, 2H), 7.14 (s, IH), 4.35 (s, 2H), 4.10 (s, 3H), 4.03 (s, IH), 3.92 (s, 3H), 2.40 (s, 3H), 1.54 (s, 3H).Example 156a was separated by Chirai HPLC (Chiralpak AD column, 5 uM, using EtOH to provide the first eluting enantiomer as Example 156b ‘H NMR (400 MHz, CDC13) delta ppm 8.15 id. ./ 2.1 Hz, IH), 7.86 (d, J = 8.7 Hz, IH), 7.56 – 7.46 (m, 3H), 7.40 id. ./ 8.0 Hz, 21 1). 7.14 (s, IH), 4.34 (s, 2H), 4.09 is, 31 1). 3.91 (s, M l). 2.40 (s, 31 1). 1.54 (s, 3H); and the second eluting enantiomer as Example 156c H NMR (400 MHz, CDC13) delta 8.15 (d, J = 2.1 Hz, IH), 7.86 (d, J = 8.7 Hz, I H), 7.55 – 7.48 (m, 3H), 7.40 (d, J = 8.1 Hz, 2H), 7.14 (s, IH), 4.35 (s, 2H), 4.10 (s, 3H), 3.92 (s, 3H), 2.45 (s, 3H), 1.54 is, 3H).
According to the analysis of related databases, 1-Methyl-1H-1,2,3-triazole, the application of this compound in the production field has become more and more popular.
Reference:
Patent; JANSSEN PHARMACEUTICA NV; LEONARD, Kristi A.; BARBAY, Kent; EDWARDS, James P.; KREUTTER, Kevin D.; KUMMER, David A.; MAHAROOF, Umar; NISHIMURA, Rachel; URBANSKI, Maud; VENKATESAN, Hariharan; WANG, Aihua; WOLIN, Ronald L.; WOODS, Craig R.; FOURIE, Anne; XUE, Xiaohua; CUMMINGS, Maxwell D.; JONES, William Moore; GOLDBERG, Steven; WO2015/57205; (2015); A1;,
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