Reference of 1338226-21-3,Some common heterocyclic compound, 1338226-21-3, name is 3-(Chloromethyl)-4-methyl-1H-1,2,4-triazol-5(4H)-one, molecular formula is C4H6ClN3O, 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.
To a 75L flask was charged a 9.63wt% solution of 3-(chloromethyl)-4-methyl-lH-l,2,4-triazol-5(4H)-one in NMP (1 1.6 kg, 7.55 mol), 3 -chloro-5 -((2-oxo-4-(trifluoromethyl)- 1 ,2-dihydropyridin-3 -yl)oxy)benzonitrile (2.00 kg, 6.29 mol), NMP (3.8 L) and 2-methyl-2-butanol (6.0 L). To the resulting suspension was slowly added N,N-diisopropylethylamine (4.38 L, 25.2 mol) over 4h. The reaction was aged 18h at ambient temperature. The reaction is considered complete when HPLC indicates <1% 3 -chloro-5 -((2-oxo-4-(trifluoromethyl)-l,2-dihydropyridin-3-yl)oxy)benzonitrile remaining. The tan solution was quenched with acetic acid (1.26 L, 22.0 mol) and aged at ambient temperature overnight. The tan solution was warmed to 70 C. Water (2.52 L) was added and the batch was seed with anhydrate Form II (134 g). The thin suspension was aged lh at 70 C. Additional water (14.3 L) was added evenly over 7 h. The slurry was aged 2h at 70 C and then slowly cooled to 20 C over 5 h. The slurry was filtered and washed with 2 : 1 NMP/water (6 L), followed by water washes (6 L x 2). The filter cake was dried over a 2 sweep to give 2.53 kg (85% yield - corrected) of a white solid that was confirmed to be crystalline Form II by X-ray powder detraction analysis.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-(Chloromethyl)-4-methyl-1H-1,2,4-triazol-5(4H)-one, its application will become more common.
Reference:
Patent; MERCK SHARP & DOHME CORP.; ITOH, Tetsuji; JEON, Ingyu; MANGION, Ian; QIAN, Gang; SHERRY, Benjamin, D.; GAUTHIER, Donald, R.; CAO, Yang; WO2014/89140; (2014); A1;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics