4-N-ethylpyridine-3,4-diamine → Ethyl-2-(2-pyrimidin-2-yl-imidazol-1-ylmethyl)-1H-imidazo[4,5-c]pyridine

HRID 895667Notes

Reaction equation

HRID 895667 reaction equation
[CH2:1]([NH:3][C:4]1[CH:9]=[CH:8][N:7]=[CH:6][C:5]=1[NH2:10])[CH3:2].C[Al](C)C.CO[C:17](=O)[CH2:18][N:19]1[CH:23]=[CH:22][N:21]=[C:20]1[C:24]1[N:29]=[CH:28][CH:27]=[CH:26][N:25]=1>ClC(Cl)C.C1(C)C=CC=CC=1>[CH2:1]([N:3]1[C:4]2[CH:9]=[CH:8][N:7]=[CH:6][C:5]=2[N:10]=[C:17]1[CH2:18][N:19]1[CH:23]=[CH:22][N:21]=[C:20]1[C:24]1[N:29]=[CH:28][CH:27]=[CH:26][N:25]=1)[CH3:2]

Participants

6

Reactant 3

HCID 120363924-N-ethylpyridine-3,4-diamineHCID 16682925TrimethylaluminumHCID 69558628(2-Pyrimidin-2-yl-imidazol-1-yl)-acetic Acid Methyl Ester

Product 1

HCID 22380330Ethyl-2-(2-pyrimidin-2-yl-imidazol-1-ylmethyl)-1H-imidazo[4,5-c]pyridineYield 29.1%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of N4-ethyl-pyridine-3,4-diamine (Justus Liebigs Ann. Chem. (1935) 518, 274, 287) (125 mg, 0.9 mmol) in dichloroethane (10 mL) is added a solution of AlMe3 in toluene (2M, 1.37 mL) dropwise under nitrogen. After addition, the mixture is stirred at room temperature for one hour and (2-pyrimidin-2-yl-imidazol-1-yl)-acetic acid methyl ester (100 mg, 0.45 mmol) is added in one portion. The reaction mixture is heated with stirring at 80° C. for 2 days. After cooled, the mixture is quenched with 5 mL of water, 2 drops of 5 N NaOH and extracted with CH2Cl2 (10 mL×5). The combined organic extracts are dried over Na2SO4, and concentrated. The residue is dissolved in 10 mL of acetic acid and the resulting mixture is heated at 100° C. overnight. After removal of acetic acid under vacuum, the residue is basified with saturated NaHCO3 solution and extracted with CH2Cl2 (10 mL×5). The combined organic extracts are dried over Na2SO4, and concentrated. The residue is purified on a silica gel column with 10:1 CH2Cl2/MeOH as eluent to yield the title compound (40 mg). 1H NMR (CDCl3) δ: 9.09 (s, 1H), 8.85 (d, 2H), 8.46 (d, 1H), 7.26-7.30 (m, 3H), 7.16 (1H), 6.39 (s, 2H), 4.25 (q, 2H), 1.15 (t, 3H).

Workup

  1. additionAfter addition
  2. temperatureThe reaction mixture is heated
  3. stirringwith stirring at 80° C. for 2 days
  4. temperatureAfter cooled
  5. customthe mixture is quenched with 5 mL of water, 2 drops of 5 N NaOH
  6. extractionextracted with CH2Cl2 (10 mL×5)
  7. dry with materialThe combined organic extracts are dried over Na2SO4
  8. concentrationconcentrated
  9. dissolutionThe residue is dissolved in 10 mL of acetic acid
  10. temperaturethe resulting mixture is heated at 100° C. overnight
  11. customAfter removal of acetic acid under vacuum
  12. extractionextracted with CH2Cl2 (10 mL×5)
  13. dry with materialThe combined organic extracts are dried over Na2SO4
  14. concentrationconcentrated
  15. customThe residue is purified on a silica gel column with 10:1 CH2Cl2/MeOH as eluent

Sources & evidence

ORD record
ord-c105ca6564464f6383137cbbbde757e7
Source dataset
uspto-grants-2005_07
Patent number
US06916827B2

Reaction notes

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