Ethylene Glycol → 4-(3-Bromo-imidazo[1,2-a]pyridin-6-ylamino)-cyclohexanol

HRID 383283Notes

Reaction equation

HRID 383283 reaction equation
[O-]P([O-])([O-])=O.[K+].[K+].[K+].[Br:9][C:10]1[N:14]2[CH:15]=[C:16](I)[CH:17]=[CH:18][C:13]2=[N:12][CH:11]=1.C(O)CO.[NH2:24][C@H:25]1[CH2:30][CH2:29][C@H:28]([OH:31])[CH2:27][CH2:26]1>C(O)(C)C.[Cu]I>[Br:9][C:10]1[N:14]2[CH:15]=[C:16]([NH:24][CH:25]3[CH2:30][CH2:29][CH:28]([OH:31])[CH2:27][CH2:26]3)[CH:17]=[CH:18][C:13]2=[N:12][CH:11]=1

Participants

7

Reactant 4

HCID 174Ethylene GlycolHCID 62657Potassium Phosphate, TribasicHCID 684848303-Bromo-6-iodoimidazo[1,2-A]pyridine2×HCID 178511715HCID 178511715, compound

Product 1

HCID 684826874-(3-Bromo-imidazo[1,2-a]pyridin-6-ylamino)-cyclohexanol

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

Copper (I) iodide (0.1 eq, 1.45 g, 7.68 mmol) and potassium phosphate tribasic (2 eq, 0.153 mol, 32.5 g) are stirred at RT under an atmosphere of argon during the addition of 3-bromo-6-iodo-imidazo[1,2-a]pyridine (Intermediate F) (25 g, 77 mmol, 1 eq) in isopropyl alcohol (200 ml), ethylene glycol (2 eq, 0.153 mol, 8.5 ml) and finally trans-4-aminocyclohexanol (2 eq, 17.5 g, 153 mmol) The reaction is heated at 80° C. for 40 hours. The majority of the solvent is removed in vacuo and the residue is diluted with water (500 ml) and extracted with EtOAc (3×500 ml). The combined organic portions are dried (MgSO4) and concentrated in vacuo. Purification by flash chromatography on silica eluting with 0-15% MeOH in EtOAc gives 4-(3-bromo-imidazo[1,2-a]pyridin-6-ylamino)-cyclohexanol; [M+H]+=310 (312)

Workup

  1. customThe majority of the solvent is removed in vacuo
  2. additionthe residue is diluted with water (500 ml)
  3. extractionextracted with EtOAc (3×500 ml)
  4. dry with materialThe combined organic portions are dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customPurification by flash chromatography on silica eluting with 0-15% MeOH in EtOAc

Sources & evidence

ORD record
ord-1d3cc9f3195149cf8d2fb6bce46ba202
Source dataset
uspto-grants-2013_02
Patent number
US08367662B2

Reaction notes

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