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

HRID 2209223Notes

Reaction equation

HRID 2209223 reaction equation
CC1C=C(C)C=C(C)C=1S([O-])(=O)=O.[NH2:14][N+:15]1[CH:20]=[C:19]([Cl:21])[N:18]=[C:17]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:16]=1.[C:30](#[N:33])[CH:31]=[CH2:32].CCN(C(C)C)C(C)C.C(C1C(=O)C(Cl)=C(Cl)C(=O)C=1C#N)#N>O1CCOCC1>[CH2:23]([O:22][C:17]1[C:16]2[N:15]([N:14]=[CH:32][C:31]=2[C:30]#[N:33])[CH:20]=[C:19]([Cl:21])[N:18]=1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

6

Reactant 4

HCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 7855AcrylonitrileHCID 81531DiisopropylethylamineHCID 1178435431-Amino-3-(benzyloxy)-5-chloropyrazin-1-ium 2,4,6-trimethylbenzenesulfonate

Product 1

HCID 1178438284-Benzyloxy-6-chloro-pyrazolo[1,5-a]pyrazine-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-c76b946a745d4aefb848ad6a3ef96089
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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