Some common heterocyclic compound, 16681-65-5, name is 1-Methyl-1H-1,2,3-triazole, molecular formula is C3H5N3, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Quality Control of 1-Methyl-1H-1,2,3-triazole
Example 25a: (4-chloro-2-ethyl-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol A solution of -butyllithium in hexanes (2.5 M, 0.17 mL, 0.43 mmol) was added dropwise to a stirring solution of 5 -methyl – 1 H- 1 ,2,3-triazole (38,3 mg, 0.461 mmol, prepared according to PCT Int. Appl., 2008098104) in tetrahydrofuran (1.5 mL) at -50 C. After 20 minutes at -50 C, a solution of (4-chloro-2-ethyl-3-(4-(trif]uoromethyl)benzyl)quinolin-6-yl)(imidazol-5-yl)methanone (0, 145 g, 0.307 mmol, Intermediate 25: step b) in tetrahydrofuran (1 .5 mL) was added dropwise. After 5 minutes at -50 C, the flask was allowed to warm to 0 C. After 30 minutes, the mixture was partitioned between half-saturated aqueous sodium chloride solution (25 mL) and ethyl acetate (50 mL). The layers were separated and the organic layer was dried with sodium sulfate. The dried solution was filtered. Silica gel (3 g) was added to the filtrate and the mixture was concentrated by rotary evaporation to afford a free-flowing powder. The powder was loaded onto a silica gel column for flash column chromatography purification. Elution with dichloromethane initially, grading to 10% methanol-dichloromethane provided the title compound as an off-white solid. The solid was further purified by chiral SFC (Chiralpak AD-H, 5 urn, 250 x 20 mm, mobile phase: 75% CO?, 25% ethanol containing 0.03% isopropylamine) to provide two enantiomers. The first eluting enantiomer was Example 25b: NMR (600 MHz, CDC13) delta ppm 8.30 (d, J ~ 2.1 Hz, IH), 8.02 (d, J = 8.8 Hz, IH), 7.57 – 7.49 (m, 3H), 7.21 (d, ./ 7.9 Hz, 21 1 ;¡¤. 7.17 (s, IH), 6.18 (s, IH), 4.91 (s, IH), 4.49 (s, 2H), 3.95 (s, 31 1). 3.40 (s, 3H), 3.00 – 2.90 (m, 2H), 2.30 (s, 3H), 1.35 – 1.28 (m, 31 1): MS (ESI): mass calcd. for C28H26CIF3 6O, 554.2; m z found, 555,2 [M+H]+. and the second eluting enantiomer was Example 25c: H NMR (600 MHz, CDC13) delta ppm 8.32 (d, J = 2.1 Hz, IH), 7.99 (d, J = 8.8 Hz, IH), 7.56 – 7.51 (m, 3H), 7.21 (d, J = 7.9 Hz, 2H), 7.12 (s. IH), 6.14 (s, i l l). 5.83 (s, i l l). 4.48 (s, 2H), 3.93 (s, 3H), 3.38 (s, 3H), 2.98 – 2.90 (m, 2H), 2.24 (s, 3H), 1 ,34 – 1.27 (m, 3H): MS (ESI): mass calcd. for C28C1F3N6Q, 554.2; m/z found, 555.0 [M+Hf.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 16681-65-5, its application will become more common.
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;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics