Electric Literature of 7170-01-6, These common heterocyclic compound, 7170-01-6, name is 3-Methyl-1H-1,2,4-triazole, 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.
Step 212.1 : To a solution of 3-methyl-1H-1,2,4-triazole (1 g) in MeCN (40ml) was added Cs2CO3 (3.72g) followed by benzyl bromoacetate (1.89ml_). The reaction mixture was stirred at RT for 1 h and evaporated to dryness. The residue was taken up in EA and washed with water, sat. NH4Cl and brine. The aq. layers were extracted with EA, the combined org. layers were dried (MgSO4), filtered off and evaporated in vacuo. The residue was purified by CC (Biotage, SNAP 100g cartridge, solvent A: DCM; solvent B: DCM/MeOH 8/2; gradient in %B: 15 for 12CV, 15 to 25 over 2CV, 25 for 3CV) to afford 2.23g of oil. The oil was purified by preparative chiral HPLC (II) to afford the two regioisomers, both as mixture of benzyl and ethyl ester that formed during the evaporation of the fractions after HPLC purification. The second eluting compound also contains the methyl ester analog due to the addition of MeOH to the fractions before evaporation. First eluting compound: (5-Methyl-[1,2,4]triazol-1-yl)-acetic acid benzyl ester (1.07g, brown oil, contains 16% of the ethyl ester analog). LC-MS (B): tR = 0.68min; [M+H]+: 232.16. 1H-NMR (CDCl3): 7.83 (s, 1 H); 7.40-7.33 (m, 5H); 5.23 (s, 2H); 4.93 (s, 2H); 2.43 (s, 3H). Roesy signal seen between CH2 at 4.93 ppm and CH3 at 2.43 ppm. Second eluting compound: (3-Methyl-[1,2,4]triazol-1-yl)-acetic acid benzyl ester (1.15g, yellow oil, contains 30% of the ethyl ester and 20% of the methyl ester analogs). LC-MS (B): tR = 0.67min; [M+H]+: 232.16. 1H-NMR (CDCl3): 8.05 (s, 1 H); 7.40-7.30 (m, 5H); 5.23 (s, 0.95H, CH2 of benzyl ester); 4.93-4.88 (3s, 2H); 4.27 (q, 0.58H, CH2 of ethyl ester); 3.81 (s, 0.65 H, CH3 of methyl ester); 2.42 (s, 3H). Roesy signal seen between CH at 8.05ppm and CH2 at 4.93-4.88ppm.
The synthetic route of 7170-01-6 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; ACTELION PHARMACEUTICALS LTD; CAROFF, Eva; KELLER, Marcel; KIMMERLIN, Thierry; MEYER, Emmanuel; WO2013/114332; (2013); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics