Imidazole → HCID 58970703, compound

HRID 598011Notes

Reaction equation

HRID 598011 reaction equation
P([O-])([O-])([O-])=O.[K+].[K+].[K+].[NH:9]1[CH:13]=[CH:12][N:11]=[CH:10]1.Br[C:15]1[CH:16]=[N:17][C:18]2[C:19]3[N:28]([CH2:29][CH:30]([CH3:32])[CH3:31])[C:27]([CH2:33][O:34][CH2:35][CH3:36])=[N:26][C:20]=3[C:21]([NH2:25])=[N:22][C:23]=2[CH:24]=1.N[C@@H]1CCCC[C@H]1N>[Cu]I.O1CCOCC1>[CH2:35]([O:34][CH2:33][C:27]1[N:28]([CH2:29][CH:30]([CH3:32])[CH3:31])[C:19]2[C:18]3[N:17]=[CH:16][C:15]([N:9]4[CH:13]=[CH:12][N:11]=[CH:10]4)=[CH:24][C:23]=3[N:22]=[C:21]([NH2:25])[C:20]=2[N:26]=1)[CH3:36]

Participants

7

Reactant 4

HCID 795ImidazoleHCID 438061,2-Diaminocyclohexane, trans-HCID 62657Potassium Phosphate, TribasicHCID 67052511HCID 67052511, compound

Product 1

HCID 58970703HCID 58970703, compoundYield 18.7%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

Copper (I) iodide (0.06 g, 0.53 mmol), potassium phosphate (1.18 g, 5.56 mmol), and imidazole (0.22 g, 3.17 mmol) were added to a glass tube. Sequential addition of 7-bromo-2-(ethoxymethyl)-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine (1.0 g, 2.64 mmol), trans-1,2-diaminocyclohexane (0.06 g, 0.53 mmol) and dioxane (9 mL) followed. The tube was flushed with nitrogen, sealed, and heated to 110° C., and the reaction mixture was stirred for 10 days. The reaction mixture was then diluted with a 1:1 mixture of chloroform and methanol (50 mL) and filtered through CELITE filter aid. The filtrate was concentrated under reduced pressure to give a black liquid, which was purified by automated flash chromatography (using a silica gel cartridge, eluting with CMA:chloroform ranging in ratios from 0:100 to 20:80), and concentrated under reduced pressure. The residue was recrystallized from diethyl ether to give 0.18 g of 2-(ethoxymethyl)-7-(imidazol-1-yl)-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine as a tan solid, mp 175-176° C.

Workup

  1. customThe tube was flushed with nitrogen
  2. customsealed
  3. additionThe reaction mixture was then diluted with a 1:1 mixture of chloroform and methanol (50 mL)
  4. filtrationfiltered through CELITE
  5. filtrationfilter aid
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customto give a black liquid, which
  8. customwas purified by automated flash chromatography (
  9. washeluting with CMA
  10. concentrationchloroform ranging in ratios from 0:100 to 20:80), and concentrated under reduced pressure
  11. customThe residue was recrystallized from diethyl ether

Sources & evidence

ORD record
ord-4c0993aff9d644f18182191d812d3d01
Source dataset
uspto-grants-2011_03
Patent number
US07897609B2

Reaction notes

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