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

HRID 1943205Notes

Reaction equation

HRID 1943205 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][C@@H:14]([CH2:15][N:16]4[CH2:21][CH2:20][C:19]([NH:23][C:24](=[O:29])[C:25]([F:28])([F:27])[F:26])([CH3:22])[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[C@H:14]([CH2:15][N:16]4[CH2:17][CH2:18][C:19]([NH:23][C:24](=[O:29])[C:25]([F:28])([F:27])[F:26])([CH3:22])[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-benzoquinoneHCID 11430Potassium CarbonateHCID 86642104N-(1-{[(2R)-4,9-Dioxo-1,2,8,9-tetrahydro-4H,7H-imidazo[1,2,3-ij]-1,8-naphthyridin-2-yl]methyl}-4-methyl-4-piperidinyl)-2,2,2-trifluoroacetamide

Product 1

HCID 86642105N-(1-{[(1R)-4,9-Dioxo-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridin-1-yl]methyl}-4-methyl-4-piperidinyl)-2,2,2-trifluoroacetamideYield 46%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of N-(1-{[(2R)-4,9-dioxo-1,2,8,9-tetrahydro-4H,7H-imidazo[1,2,3-ij]-1,8-naphthyridin-2-yl]methyl}-4-methyl-4-piperidinyl)-2,2,2-trifluoroacetamide (375 mg, 0.909 mmol) in 1,4-dioxane (20 ml) at rt was treated with DDQ (248 mg, 1.091 mmol) and then heated at 80° C. for 1 h. The reaction was then cooled to rt. The reaction mixture was treated with saturated aqueous K2CO3 (5%, 100 ml), then with DCM (100 ml) and the mixture filtered through Kieselguhr. The organic fraction was separated and the aqueous layer extracted with DCM (2×100 ml). The combined organic solvents were then dried (MgSO4), filtered and evaporated to give the crude product as a yellow oil. Chromatography on silica (0-10% methanol:DCM, Rf=0.4 in 10% MeOH/DCM) gave the product as a clear oil (171 mg, 46%).

Workup

  1. temperatureThe reaction was then cooled to rt
  2. filtrationwith DCM (100 ml) and the mixture filtered through Kieselguhr
  3. customThe organic fraction was separated
  4. extractionthe aqueous layer extracted with DCM (2×100 ml)
  5. dry with materialThe combined organic solvents were then dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customto give the crude product as a yellow oil

Sources & evidence

ORD record
ord-f92e8ae37a564a30bc5d2df720aa50c8
Source dataset
uspto-grants-2013_03
Patent number
US08389524B2

Reaction notes

Loading…