Cesium carbonate → tert-Butyl 8-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-3,4-dihydropyrazino[1,2-a]benzimidazole-2(1H)-carboxylate

HRID 882062Notes

Reaction equation

HRID 882062 reaction equation
Br[C:2]1[CH:21]=[CH:20][C:5]2[N:6]3[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][C:7]3=[N:8][C:4]=2[CH:3]=1.[CH2:22]([O:29][C:30]1[CH:35]=[CH:34][NH:33][C:32](=[O:36])[CH:31]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.CN[C@@H]1CCCC[C@H]1NC.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C(Cl)Cl.CO.[NH4+].[OH-].[Cu]I>[CH2:22]([O:29][C:30]1[CH:35]=[CH:34][N:33]([C:2]2[CH:21]=[CH:20][C:5]3[N:6]4[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][C:7]4=[N:8][C:4]=3[CH:3]=2)[C:32](=[O:36])[CH:31]=1)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 36077244-Benzyloxy-2(1H)-pyridoneHCID 67988850tert-Butyl 8-bromo-3,4-dihydropyrazino[1,2-a]benzimidazole-2(1H)-carboxylate

Product 1

HCID 67988846tert-Butyl 8-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-3,4-dihydropyrazino[1,2-a]benzimidazole-2(1H)-carboxylateYield 51.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolventHCID 21896990Dichloromethane methanol ammonium hydroxideSolvent

Conditions

Temperature
110 °C

Procedure

tert-Butyl 8-bromo-3,4-dihydropyrazino[1,2-a]benzimidazole-2(1H)-carboxylate (188 mg, 0.534 mmol), 4-(benzyloxy)pyridin-2(1H)-one (118 mg, 0.589 mmol), CuI (203 mg, 1.07 mmol), trans-N,N′dimethylcyclohexane-1,2-diamine (76 mg, 0.54 mmol) and Cs2CO3 (192 mg, 0.591 mmol) in 1,4-dioxane (15 mL) were sparged with a nitrogen stream for 45 min and then stirred at 110° C. for 16 h. The mixture was diluted with 90:9:1 CH2Cl2/MeOH/NH4OH (50 mL) and washed with brine (3×50 mL). The resulting solution was dried over Na2SO4 and concentrated under reduced pressure to give a crude residue. The residue was purified by column chromatography eluting with methylene chloride and a 9:1 methanol/ammonium hydroxide mixture; gradient 100% methylene chloride to 85% methylene chloride, to provide the title compound (131 mg, 28%) as a brown solid: ESI MS m/z 473 [M+H]+.

Workup

  1. washwashed with brine (3×50 mL)
  2. dry with materialThe resulting solution was dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customto give a crude residue
  5. customThe residue was purified by column chromatography
  6. washeluting with methylene chloride

Sources & evidence

ORD record
ord-5957ed0d1b204d83aed32ca4847cb833
Source dataset
uspto-grants-2015_03
Patent number
US08993765B2

Reaction notes

Loading…