2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → 1,1-Dimethylethyl {1-[(4,9-dioxo-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridin-1-yl)methyl]-4-piperidinyl}carbamate

HRID 1943170Notes

Reaction equation

HRID 1943170 reaction equation
[O:1]=[C:2]1[CH:11]=[CH:10][C:9]2[CH2:8][CH2:7][C:6](=[O:12])[N:5]3[CH2:13][CH:14]([CH2:15][N:16]4[CH2:21][CH2:20][CH:19]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:18][CH2:17]4)[N:3]1[C:4]=23.C(C1C(=O)C(Cl)=C(Cl)C(=O)C=1C#N)#N.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1>[O:12]=[C:6]1[CH:7]=[CH:8][C:9]2[CH:10]=[CH:11][C:2](=[O:1])[N:3]3[CH:14]([CH2:15][N:16]4[CH2:17][CH2:18][CH:19]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:27])([CH3:26])[CH3:28])[CH2:20][CH2:21]4)[CH2:13][N:5]1[C:4]=23

Participants

5

Reactant 3

HCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinone4×HCID 11430Potassium Carbonate2×HCID 58001733HCID 58001733, compound

Product 1

HCID 580017981,1-Dimethylethyl {1-[(4,9-dioxo-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridin-1-yl)methyl]-4-piperidinyl}carbamateYield 54.9%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 1,1-dimethylethyl {1-[(4,9-dioxo-1,2,8,9-tetrahydro-4H,7H-imidazo[1,2,3-ij]-1,8-naphthyridin-2-yl)methyl]-4-piperidinyl}carbamate (2:1 mixture of R:S) (1.83 g, 4.55 mmol) and DDQ (1.6 g, 6.83 mmol) in 1,4-dioxane (100 ml) was stirred at 60° C. under argon overnight. More DDQ (1.6 g, 6.83 mmol) was added and the reaction was stirred at 60° C. for another 1 h. The reaction was cooled to room temperature, treated with 5% aqueous solution of potassium carbonate (600 ml) and extracted with 20% methanol/dichloromethane (3×500 ml). The combined organic extracts were dried over magnesium sulphate, filtered and evaporated to afford the crude as a brown oil. LCMS showed that there was still ˜8% of starting material left so the oil was combined with more starting material (220 mg) recovered from the aqueous in the previous step and was dissolved in 1,4-dioxane (100 ml), treated with 1 eq. of DDQ and heated at 60° C. for 1 h. LCMS showed that the reaction was not complete so 0.5 g of DDQ was added and the reaction was stirred at 60° C. for 0.5 h. A small work-up showed that the reaction was complete so the reaction was treated with 5% aqueous solution of potassium carbonate (500 ml) and extracted with 20% methanol/dichloromethane (2×500 ml). The combined organic extracts were dried over magnesium sulphate, filtered and evaporated to afford the product as a light brown foam (1 g, 50%).

Workup

  1. stirringthe reaction was stirred at 60° C. for another 1 h
  2. temperatureThe reaction was cooled to room temperature
  3. extractionextracted with 20% methanol/dichloromethane (3×500 ml)
  4. dry with materialThe combined organic extracts were dried over magnesium sulphate
  5. filtrationfiltered
  6. customevaporated
  7. customto afford the crude as a brown oil
  8. waitleft so the oil
  9. customrecovered from the aqueous in the previous step
  10. dissolutionwas dissolved in 1,4-dioxane (100 ml)
  11. temperatureheated at 60° C. for 1 h
  12. additionwas added
  13. stirringthe reaction was stirred at 60° C. for 0.5 h
  14. extractionextracted with 20% methanol/dichloromethane (2×500 ml)
  15. dry with materialThe combined organic extracts were dried over magnesium sulphate
  16. filtrationfiltered
  17. customevaporated

Sources & evidence

ORD record
ord-e6ca1e300e024f89828d827955309d0c
Source dataset
uspto-grants-2013_03
Patent number
US08389524B2

Reaction notes

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