Diethyl Ether → tert-Butyl 4-(5-(hydroxy(thiophen-2-yl)methyl)-[1,2,4]triazolo[4,3-a]pyrazin-8-yl)piperazine-1-carboxylate

온도

0 °C

A 250 mL 3-necked round bottom flask was charged with thiophene (0.63 g, 7.5 mmol) and dry ethyl ether (10 mL). To the above was added dropwise nBuLi solution (2.5 M in hexane, 3 mL, 7.5 mmol) at 0° C. The mixture was stirred at 0° C. for 1 h, and was then cooled to −78° C. A solution of tert-butyl 4-(5-formyl-[1,2,4]-triazolo[4,3-a]pyrazin-8-yl)piperazine-1-carboxylate (1.0 g, 3.0 mmol) in dry CH2Cl2 (10 mL) was added dropwise at that temperature. The resulting mixture was stirred at −78° C. for 0.5 h, and then quenched by slow addition of methanol (10 mL). The reaction mixture was poured into saturated aqueous NH4Cl (100 mL) and extracted with ethyl ether (100 mL×2). The combined organic layers were washed with saturated aqueous NaHCO3 (100 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was further purified by flash column chromatography on silica gel with 1% MeOH in CH2Cl2, to afford 0.90 g (72%) of the product as a white solid. MS m/z: 417 (M+H+).

1. temperaturewas then cooled to −78° C
2. stirringThe resulting mixture was stirred at −78° C. for 0.5 h
3. customquenched by slow addition of methanol (10 mL)
4. additionThe reaction mixture was poured into saturated aqueous NH4Cl (100 mL)
5. extractionextracted with ethyl ether (100 mL×2)
6. washThe combined organic layers were washed with saturated aqueous NaHCO3 (100 mL)
7. dry with materialdried over anhydrous Na2SO4
8. concentrationconcentrated in vacuo
9. customThe residue was further purified by flash column chromatography on silica gel with 1% MeOH in CH2Cl2

ORD 기록

ord-034d0942cc814936b42b274de77cd439

출처 데이터셋

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08569300B2