# US 2014/0155619 A1 · Process for preparation of 1,2,3-triazole-4 carboxamides > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0155619 A1 - Document ID: US20140155619A1 - Status: Published application - Kind: A1 - Application number: 14/095,640 - Filed: 2013-12-03 - Published: 2014-06-05 - Earliest claimed: 2012-12-03 - Assignees: Taro Pharmaceutical Industries Ltd. - Applicants: Taro Pharmaceutical Industries Limited - Inventors: Shimon Cherynyak; Rosa Cyjon; Ilana Ozer - Web page: https://patentgrep.com/patent/US20140155619A1 ## CPC - C07D 249/04: 1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## Abstract The invention relates to the preparation of 1,2,3-triazole-4-carboxamide of general Formula I: wherein R1 and R2 may be the same or different and are selected from H, F, Cl, Br, I, OR, C(O)R, NH2, NHR or NR2. R can be a linear or branched alkyl group, for example a C1-C4 alkyl group. In exemplary embodiments, R1 and R2 are independently selected from H, F, Cl, Br, and I. The compound of Formula I can be Rufinamide. ## Claims ### Claim 1 A process for the preparation of a 1,2,3-triazole-4-carboxamide of formula I comprising: (a) reacting a benzyl chloride of general formula III with an azide to obtain a benzylazide of general formula IV, wherein R1 and R2 are as defined above; (b) reacting the benzylazide of general Formula IV with a 2-halideacrylamide of general Formula V, wherein X is selected from Cl, Br and I, to obtain the 1,2,3-triazole-4-carboxamide of general Formula I; and (c) isolating the obtained 1,2,3-triazole-4-carboxamide of general Formula I wherein R1 and R2 are independently selected from the group consisting of H, F, Cl, Br, I, OR, C(O)R, NH2, NHR or NR2, wherein R is a linear or branched alkyl group. ### Claim 2 (depends on 1) The process according to claim 1, wherein both R1 and R2 are F. ### Claim 3 (depends on 1) The process according to claim 1, wherein the azide is an alkali metal azide. ### Claim 4 (depends on 3) The process according to claim 3, wherein the alkali metal azide is sodium azide or potassium azide. ### Claim 5 (depends on 1) The process according to claim 1, wherein the 2-halideacrylamide is 2-chloroacrylamide. ### Claim 6 (depends on 1) The process according to claim 1, wherein reaction of step (i) is carried out in the presence of a polar protic solvent. ### Claim 7 (depends on 6) The process according to claim 6, wherein the polar protic solvent is C1-C4 alkanol, water, or mixtures thereof. ### Claim 8 (depends on 1) The process according to claim 1, wherein reaction step (ii) is carried out in the presence of a solvent having boiling point of at least about 60° C., or in the absence of any solvent. ### Claim 9 (depends on 8) The process according to claim 8, wherein reaction step (ii) is carried out in the presence of C1-C4 alkanol or dioxane. ### Claim 10 (depends on 1) The process according to claim 1, wherein reaction step (ii) is conducted in the presence of a base selected from sodium bicarbonate, potassium carbonate, potassium bicarbonate, potassium tert- butoxide and triethylamine. ### Claim 11 A process for the preparation of rufinamide of Formula II, comprising: (a) reacting 2,6-difluorobenzyl chloride with sodium azide to obtain 2,6-difluorobenzylazide; (b) reacting 2,6-difluorobenzylazide with 2-chloroacrylamide to form rufinamide; and isolating the obtained rufinamide. ### Claim 12 (depends on 11) The process according to claim 11, wherein reaction of step (i) is carried out in the presence of water. ### Claim 13 (depends on 11) The process according to claim 11, wherein reaction step (ii) is carried out in the presence of ethanol or dioxane as a solvent, or in the absence of any solvent. ### Claim 14 (depends on 11) The process according to claim 11, wherein the reaction between 2,6-difluorobenzyl chloride and sodium azide is performed at a temperature between 0° C. to the reflux temperature of the solvent in the reaction mixture. ### Claim 15 (depends on 12) The process according to claim 12, wherein the reaction between 2,6-difluorobenzylazide and 2-chloroacrylamide is carried out at a temperature ranging from about 0° C. to the reflux temperature of the solvent in the reaction mixture. ### Claim 16 (depends on 11) The process according to claim 11, wherein the equivalent ratio between the 2,6-difluorobenzyl chloride and the sodium azide is between about 1:1 to about 1:3. ### Claim 17 A process for the preparation of a 1,2,3-triazole-4-carboxamide of formula I wherein R1 and R2 are independently selected from H, F, Cl, Br and I, comprising: reacting a benzylazide of general Formula IV wherein R1 and R2 are independently selected from H, F, Cl, Br and I, with a 2-halideacrylamide of general Formula V wherein X is selected from Cl, Br and I, to obtain the 1,2,3-triazole-4-carboxamide of general Formula I; and isolating the obtained 1,2,3-triazole-4-carboxamide of general Formula I; wherein R1 and R2 are independently selected from the group consisting of H, F, Cl, Br, I, OR, C(O)R, NH2, NHR or NR2, wherein R is a linear or branched alkyl group. ### Claim 18 (depends on 17) The process according to claim 17, wherein both R1 and R2 are F. ### Claim 19 (depends on 17) The process according to claim 17, wherein the 2-halideacrylamide is 2-chloroacrylamide. ### Claim 20 (depends on 17) The process according to claim 17, wherein reaction step (i) is carried out in the presence of a solvent having boiling point of at least about 60° C., or in the absence of any solvent. ### Claim 21 (depends on 20) The process according to claim 20, wherein reaction step (i) is carried out in the presence of C1-C4 alkanol or dioxane. ### Claim 22 (depends on 17) The process according to claim 17, wherein reaction step (i) is conducted in the presence of a base selected from sodium bicarbonate, potassium carbonate, potassium bicarbonate, potassium tert-butoxide and triethylamine.