3-(5,7-DiMethyl-[1,2,4]triazolo[1,5-a]pyriMidin-2-yl)propanoic acid synthesis

Yield:901735-11-3 68%

Reaction Conditions:

Stage #1: succinic acid anhydride;1-aminoguanidine hydrochloride at 190; for 1 h;
Stage #2: with sodium hydroxide in water at 120; for 1.5 h;
Stage #3: acetylacetonewith acetic acid in ethanol; for 7 h;Reflux;

Steps:

3-(5,7-Dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)propanoicAcid (23)

A mixture of aminoguanidine hydrochloride21 (25.0 g, 226 mmol) and succinic anhydride 22 (25.0 g,250 mmol) was stirred at 190°C for 1 h. After cooling at roomtemperature, to the reaction mixture were added sodiumhydroxide (27.0 g, 675 mmol) and H2O (67 mL). The mixturewas stirred at 120°C for 1.5 h. After cooling, to the reactionmixture were added conc. HCl aqueous solution (37 mL) andH2O (25 mL) at room temperature, and the mixture was stoodovernight. The resulting precipitate under ice-bath coolingwas collected by filtration. To the residue were added EtOH(400 mL), acetylacetone (20.0 mL, 194 mmol) and AcOH(2.00 mL, 35.0 mmol), and the mixture was stirred underreflux for 7 h. After cooling at room temperature, to the mixturewere added H2O (30 mL) and sodium hydroxide (10.0 g,250 mmol), and the mixture was stirred at room temperaturefor 2 h. The mixture was filtered and the filtrate was concentratedin vacuo lightly. To the solution was added conc. HClaqueous solution (20 mL) and the mixture was cooled underice-bath. The resulting precipitate was collected by filtrationto give 23 (33.7 g, 68%) as a colorless solid. 1H-NMR(DMSO-d6) δ: 2.55 (s, 3H), 2.69 (d, 3H, J=0.9 Hz), 2.76 (t, 2H,J=7.3 Hz), 3.05 (t, 2H, J=7.4 Hz), 7.10 (d, 1H, J=0.9 Hz), 12.20(br s, 1H); MS (ESI) m/z 221 [M+H]+.

References:

Chino, Ayaka;Seo, Ryushi;Amano, Yasushi;Namatame, Ichiji;Hamaguchi, Wataru;Honbou, Kazuya;Mihara, Takuma;Yamazaki, Mayako;Tomishima, Masaki;Masuda, Naoyuki [Chemical and Pharmaceutical Bulletin,2018,vol. 66,# 3,p. 286 - 294]