Application of 767340-03-4, A common heterocyclic compound, 767340-03-4, name is (2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine, molecular formula is C16H13F6N5O, 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.
Into a 500 ml flask were charged chloro(l,5-cyclooctadiene)rhodium(l) dimer {[Rh(cod)CI]2} (292 mg, 1.18 mmol) and (R,S) t-butyl Josiphos (708 mg, 1.3 mmal) under a nitrogen atmosphere. Degassed MeOH was then added (200 ml_) and the mixture was stirred at room temperature for 1 h. Into a 4L hydrogenator was charged the enamine amide (VII) (118 g, 0.29 mal), MeOH (1 L). The catalyst solution was then transferred to the hydrogenator. After degassing three times, the enamine amide was hydrogenated under 200 psi hydrogen at 50 C for 13 h. The obtained methanol solution was concentrated and switched to methyl t-butyl ether (MTBE) (45 ml_). Into this solution was added aqueous H3P04 solution (0.5 M, 95 ml_). After separation of the layers, 3N NaOH (35 ml_) was added to the water layer, which was then extracted with MTBE (180 ml_ + 100 ml_). The MTBE solution was concentrated and solvent switched to hot toluene (180 ml_, about 75 C). The toluene solution was then cooled to O C. The crystals were isolated by filtration to obtained Sitagliptin (I) (13 g, yield 72%, 98-99% ee);
The synthetic route of 767340-03-4 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; F.I.S. – FABBRICA ITALIANA SINTETICI S.P.A.; SHI, Terry; LOU, Sam; DE LUCCHI, Ottorino; PADOVAN, Pierluigi; (45 pag.)WO2019/158285; (2019); A1;,
Pyrazine – Wikipedia,
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