Hydrochloric Acid → 2-{2-[3-(1H-imidazol-1-yl)phenyl]-2H-tetrazol-5-yl}pyridine

HRID 734256Notes

Reaction equation

HRID 734256 reaction equation
I[C:2]1[CH:3]=[C:4]([N:8]2[N:12]=[N:11][C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[NH:19]1[CH:23]=[CH:22][N:21]=[CH:20]1.C(=O)([O-])[O-].[K+].[K+].NC1CCCCC1N.Cl.CCOCC>C(Cl)Cl.CCOCC.[Cu]I>[N:19]1([C:2]2[CH:3]=[C:4]([N:8]3[N:12]=[N:11][C:10]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=4)=[N:9]3)[CH:5]=[CH:6][CH:7]=2)[CH:23]=[CH:22][N:21]=[CH:20]1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 795ImidazoleHCID 3283Diethyl EtherHCID 46101,2-DiaminocyclohexaneHCID 11430Potassium CarbonateHCID 99244722-[2-(3-iodophenyl)-2H-tetrazol-5-yl]pyridine

Product 1

HCID 686173542-{2-[3-(1H-imidazol-1-yl)phenyl]-2H-tetrazol-5-yl}pyridine

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 21881112Ethyl ether methylene chlorideSolvent

Conditions

Temperature
100 °C

Procedure

2-[2-(3-Iodophenyl)-2H-tetrazol-5-yl]pyridine (520 mg, 1.5 mmol), imidazole (133 mg, 2.0 mmol), potassium carbonate (435 mg, 3.2 mmol), copper (I) iodide (57 mg, 0.3 mmol) and 1,2-diamino cyclohexane (90 μL, 0.8 mmol) were weighed into a flask and flushed with Ar(g). Dry dioxane (0.7 mL) was added and the reaction mixture heated at 100° C. for 18 h. The reaction mixture was then poured into NH4OH (10% in H2O), NH4Cl (sat aq) (1/1, 10 mL) and shaken with EtOAc (30 mL). The organic layer was separated and the aqueous layer extracted with EtOAc (3×30 mL), the combined organics were dried over Na2SO4, filtered and concentrated onto silica gel. Purification by liquid chromatography on silica gel (hexane:EtOAc=90:10) gave a yellow solid. This was recrystallized from EtOAc/Hexane to give yellow crystals which were dissolved in CH2Cl2/Et2O and HCl in ether (1.5 equiv) was added. The resulting precipitate was filtered off to afford 2-{2-[3-(1H-imidazol-1-yl)phenyl]-2H-tetrazol-5-yl}pyridine as a yellow solid. 1H NMR ((CD3)2SO, 300 MHz) δ 9.94 (s, 1H), 8.23-8.84 (m, 1H), 8.68-8.69 (m, 1H), 8.48-8.49 (m, 1H), 8.39-8.42 (m, 1H), 8.30-8.33 (m, 1H) 8.07-8.13 (m, 2H), 7.97-8.03 (m, 2H), 7.63-7.67 (m, 1H). MS (ESI) 262.2 (MH-N2)+.

Workup

  1. customflushed with Ar(g)
  2. additionDry dioxane (0.7 mL) was added
  3. additionThe reaction mixture was then poured into NH4OH (10% in H2O), NH4Cl (sat aq) (1/1, 10 mL)
  4. customThe organic layer was separated
  5. extractionthe aqueous layer extracted with EtOAc (3×30 mL)
  6. dry with materialthe combined organics were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated onto silica gel
  9. customPurification by liquid chromatography on silica gel (hexane:EtOAc=90:10)
  10. customgave a yellow solid
  11. customThis was recrystallized from EtOAc/Hexane
  12. customto give yellow crystals which
  13. filtrationThe resulting precipitate was filtered off

Sources & evidence

ORD record
ord-0f6ac53acb1941ef991291f0275ca43b
Source dataset
uspto-grants-2009_09
Patent number
US07592337B2

Reaction notes

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