Reference of 233278-56-3, A common heterocyclic compound, 233278-56-3, name is 5,6,7,8-Tetrahydro[1,2,4]triazolo[1,5-a]pyrazine, molecular formula is C5H8N4, 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.
Parallel preparation of Examples 165-195: To a set of vials containing the chloropyrimidine core from Scheme H (25 mg, 0.056 mmol) in DMSO (0.3 mL) was individually added the requisite amine (0.067 mmol) and diisopropylethylamine (0.039 mL, 0.223 mmol). The vials were capped and the mixtures were heated to 1 10C with stirring for 3 hours. The mixtures were cooled to RT. Water (2 mL) was added to each vial. The aqueous phase from each vial was extracted with DCM (2 x 1 mL). The organic layers from each vial were transferred to a clean vial and the solvent was removed in vacuo. To each vial was then added THF:MeOH (1 :3, 1 mL) followed by HCI (4 N in dioxane, 0.20 mL, 0.80 mmol). The vials were capped and the solutions were heated to 70C for 0.5 h. The solutions were allowed to cool to RT and the solvent was then removed from the vials in vacuo. Each crude product was redissolved in 1 mL of DMSO and filtered. The crude products (excluding Example 195) were purified by mass triggered HPLC using the following conditions: [Waters XBridge CI 8 column, 5muiotaeta, 19×100 mm, gradient ranges from 10 initial to 60-70% MeCN (0.1% NH4OH) in water (0.1% NH4OH) 25 mL/min, 8 min run time] to provide the Examplesl65-190. Examples 191-194 were repurified using the following conditions: [Waters Sunfire CI 8 column, 5muetaiota, 19×100 mm, gradient ranges of 10% initial to 70-95% MeCN (0.1% TFA) in water (0.1% TFA) 25 mL/min, 8 min run time]. Example 195 was purified using the following condition: [Waters Sunfire CI 8 column, 5muetaalpha, 19×100 mm, gradient 10% to 50% MeCN (0.1% formic acid) in water (0.1 % formic acid) 25 mL/min, 8 min run time]. Table 11: Parallel preparation of Examples 165-195.
The synthetic route of 233278-56-3 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; MERCK SHARP & DOHME CORP.; MILLER, Michael; BASU, Kallol; DEMONG, Duane; SCOTT, Jack; LI, Wei; STAMFORD, Andrew; POIRIER, Marc; TEMPEST, Paul; WO2014/137723; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem