Statistics shows that 1-Methyl-1H-1,2,3-triazole-5-carbaldehyde is playing an increasingly important role. we look forward to future research findings about 202931-88-2.
Application of 202931-88-2, These common heterocyclic compound, 202931-88-2, name is 1-Methyl-1H-1,2,3-triazole-5-carbaldehyde, its 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.
Example 5a: (3-(4-(1H-Pyrazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(1-methyl-1,2,3-triazol-5-yl)methanolA solution of n-butyliithium in hexanes (1.6 M, 0.71 mL, 1.1 mmol) was added dropwise to a stirring solution of 3-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-4-chloro-2-methoxyquinoline (490 nig, 1.1 mmol, Intermediate 4: step d) in tetrahydrofuran (11 mL) at -78 C. After 2 minutes, a solution of 1-methyl-1H-1,2,3-triazole-5-carbaldehyde (140 mg, 1.1 mmol, Intermediate 18) in tetrahydrofuran (1 mL) was added dropwise. After 5 minutes, the flask was placed into an ice-water bath. After 1 hour, water (10 mL) and ethyl acetate (60 mL) were added. The biphasic mixture was stirred for 10 minutes. Half-saturated aqueous sodium chloride solution (50 mL) was added and the layers were separated. The organic layer was dried with sodium sulfate and the dried solution was filtered. Silica, gel (4 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 100% hexanes initially, grading to 100% ethyl acetate provided the title compound as a white foam which was impure. The foam was suspended in methanol (20 mL) and the suspension was sonicated for 5 minutes. The solids were collected by filtration and rinsed with methanol (5 mL). The collected solids were dried to provide the title compound as a white solid. 1H NMR (600 MHz, DMSO-d6) delta ppm 8.42 (d, J = 2.5 Hz, 1H), 8.21 (d, J = 1.8 Hz, 1H), 7.86 (d, J = 8.6 Hz, 1H), 7.75-7.71 (m, 2H), 7,72-7.67 (m, 2H), 7.37-7.32 (m, 3H), 6.55 (d, J = 5.2 Hz, 1H), 6.53-6.49 (m, 1 H), 6.22 (d, J = 5.2 Hz, 1H), 4.30 (s, 2H), 4.04 (s, 3H), 3.97 (s, 3H); MS (ESI): mass calcd. for C24H21ClN6O2; 460.1 ; m/z found, 461.1 [M+H]+.(3-(4-(1H-Pyrazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol was purified by chiral SFC (Chiralpak A, 5 mum, 250 x 20 mm, mobile phase: 55% CO2, 45% methanol) to provide two enantiomers. Each enantiomer was further purified by preparative liquid chromatography (stationary phase: irregular 1 5-40 mum, 30 g Merck, mobile phase: 95% dichloromethane, 5% methanol). The first eluting enantiomer off the chiral column was Example 5b: 1H NMR (400 MHz, CDCl3) delta ppm 8.17 (d, J = 2,3 Hz, 1H). 7.90 – 7.82 (m, 2H), 7.68 (d, J = 1.7 Hz, 1H), 7.60 – 7.53 (m, 3H), 7.41 (d, J = 1.5 Hz, 1H), 7.40 – 7.33 (m, 2H), 6.46 – 6.39 (m, I H), 6.14 (s, 1H), 4.33 (s, 2H), 4.10 (s, 3H), 3.99 (s, 3H), 2.92 (br s, 1H): MS (ESI): mass calcd. for C24H21ClN6O2, 460.1 ; m/z found, 460.9 [M+H]+and the second eluting enantiomer was Example 5c: 1H NMR (400 MHz, CDCl3) delta ppm 8.17 (d, J = 1.9 Hz, 1H), 7.90- 7.82 (m, 2H). 7.68 i d. J = 1.7 Hz, 1H), 7.60 – 7.52 (m, 3H), 7.41 (s, 1H), 7.40 – 7.33 (m, 2H). 6.46 – 6.40 (m, 1H), 6.14 (s, 1H), 4.33 is. 2H), 4.10 (s, 3H), 3.99 (s, 3H), 2.92 (br s, 1H); MS (ESI): mass calcd. for C24H21ClN6O2, 460.1 ; m/z found, 460.9 [M+H]+.
Statistics shows that 1-Methyl-1H-1,2,3-triazole-5-carbaldehyde is playing an increasingly important role. we look forward to future research findings about 202931-88-2.
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.; WO2015/57206; (2015); A1;,
1,2,3-Triazole – Wikipedia,
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