Carbamate → 1,1-Dimethylethyl (1-{[(1R)-4,9-dioxo-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridin-1-yl]methyl}-4-piperidinyl)carbamate

HRID 420673Notes

Reaction equation

HRID 420673 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][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+].C(=O)([O-])N>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][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

6

Reactant 4

HCID 276CarbamateHCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinone2×HCID 11430Potassium CarbonateHCID 582008841,1-dimethylethyl (1-{[(2R)-4,9-dioxo-1,2,8,9-tetrahydro-4H,7H-imidazo[1,2,3-ij]-1,8-naphthyridin-2-yl]methyl}-4-piperidinyl)carbamate

Product 1

HCID 582009021,1-Dimethylethyl (1-{[(1R)-4,9-dioxo-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridin-1-yl]methyl}-4-piperidinyl)carbamateYield 27%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
120 °C

Procedure

A solution of 1,1-dimethylethyl (1-{[(2R)-4,9-dioxo-1,2,8,9-tetrahydro-4H,7H-imidazo[1,2,3-ij]-1,8-naphthyridin-2-yl]methyl}-4-piperidinyl)carbamate (5.710 g, 14.19 mmol) in 1,4-dioxane (50 ml) at rt was treated with DDQ (4.83 g, 21.28 mmol) and then heated at 120° C. for 1 h. The reaction was then cooled to rt. The reaction mixture was treated with saturated aqueous K2CO3 (5%, 1000 ml) and extracted with DCM (3×500 ml). The combined organic solvents were then dried (MgSO4), filtered, evaporated to give the crude product as a brown solid. The reaction was repeated using a further portion of carbamate (2.889 g, 7.18 mmol) in 1,4-dioxane (50 ml) with DDQ (2.444 g, 10.77 mmol). The reaction was performed and worked up as above and the combined residues were chromatographed (0-100% EtOAc:40-60 Petroleum ether then 0-20% MeOH:EtOAc) to give the product as a brown solid (1.532 g, 18%).

Workup

  1. temperatureThe reaction was then cooled to rt
  2. extractionextracted with DCM (3×500 ml)
  3. dry with materialThe combined organic solvents were then dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated
  6. customto give the crude product as a brown solid
  7. customwere chromatographed (0-100% EtOAc

Sources & evidence

ORD record
ord-e55f57df1f0f4a8f8b60b0dcae0cb786
Source dataset
uspto-grants-2012_01
Patent number
US08097628B2

Reaction notes

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