Ethyl orthoformate → 4-chloro-1-methyl-1H-imidazo(4,5-c)pyridine

HRID 913

Reaction equation

HRID 913 reaction equation
[NH2:1][C:2]1[C:3]([Cl:10])=[N:4][CH:5]=[CH:6][C:7]=1[NH:8][CH3:9].[CH:11](OCC)(OCC)OCC>OS(O)(=O)=O>[Cl:10][C:3]1[C:2]2[N:1]=[CH:9][N:8]([CH3:11])[C:7]=2[CH:6]=[CH:5][N:4]=1

Participants

4

Reactant 2

HCID 31214Ethyl orthoformateHCID 9151802-Chloro-N4-methylpyridine-3,4-diamine

Product 1

HCID 9487924-chloro-1-methyl-1H-imidazo(4,5-c)pyridineYield 91.1%

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidCatalyst

Procedure

To a heterogeneous mixture of 3-amino-2-chloro-4-methylaminopyridine (5.9 g, 37 mmol) and triethyl orthoformate (12.92 mL, 87.2 mmol) was added 5 drops of conc. H2SO4. A short path distillation apparatus was attached. The reaction flask was lowered into a hot oil bath and stirred at 110° C. to 190° C. The time spent heating was 20-25 minutes. On cooling, the thick residue was dissolved in CH2Cl2 (40 mL) and was allowed to stir overnight with a little CaO. The solid was removed by filtration and the filtrate was concentrated. Flash chromatography on silica gel eluting with (CH2Cl2 /CH3OH, 95:5) gave 5.65 g (91%) of 4-chloro-1-methyl-1H-imidazo[4,5-c]pyridine as a light yellow solid: mp 127°-131° C.; MS 167 (M+).

Workup

  1. distillationA short path distillation apparatus
  2. customThe reaction flask was lowered into a hot oil bath
  3. temperatureThe time spent heating
  4. temperatureOn cooling
  5. dissolutionthe thick residue was dissolved in CH2Cl2 (40 mL)
  6. stirringto stir overnight with a little CaO
  7. customThe solid was removed by filtration
  8. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-6c6336c7aeca4c6480e93df00f4ca622
Source dataset
uspto-grants-1998_03
Patent number
US05723468

Linked notes

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