2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → 4-Benzyloxy-6-chloro-pyrazolo[1,5-a]pyrazine-3-carbonitrile

1-amino-3-(benzyloxy)-5-chloropyrazin-1-ium 2,4,6-trimethylbenzenesulfonate (5.34) (657 mg, 1.51 mmol) was suspended in 1,4-dioxane (5.75 mL) and acrylonitrile (0.23 mL, 3.5 mmol) was added followed by iPr2NEt (0.32 mL, 1.9 mmol). The resulting mixture was stirred for 1.75 h at r.t. and DDQ (720 mg, 3.2 mmol) was added in one portion. The resulting mixture was stirred an additional 1 h and was then partitioned between EtOAc, water and brine. The phases were separated and the aqueous phase was extracted with EtOAc. The combined organic phase was dried over Na2SO4, filtered, and concentrated. The concentrate was purified by silica gel chromatography (0-20% EtOAc in hexanes) to provide 4-(benzyloxy)-6-chloropyrazolo[1,5-a]pyrazine-3-carbonitrile. 1H NMR (400 MHz, Chloroform-d) δ 8.22 (s, 1H), 8.18 (s, 1H), 7.61-7.55 (m, 2H), 7.45-7.39 (m, 2H), 7.39-7.33 (m, 1H), 5.67 (s, 2H).

1. stirringThe resulting mixture was stirred an additional 1 h
2. customwas then partitioned between EtOAc, water and brine
3. customThe phases were separated
4. extractionthe aqueous phase was extracted with EtOAc
5. dry with materialThe combined organic phase was dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe concentrate was purified by silica gel chromatography (0-20% EtOAc in hexanes)

ORD record

ord-c76b946a745d4aefb848ad6a3ef96089

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09376441B2