Ammonium Hydroxide → 5-chloro-2-ethyl-7-methyl-3H-Imidazo[4,5-b]pyridine

HRID 1029585Notes

Reaction equation

HRID 1029585 reaction equation
[CH2:1]([C:3]1[NH:4][C:5]2[C:6]([N:13]=1)=[N+:7]([O-])[CH:8]=[CH:9][C:10]=2[CH3:11])[CH3:2].O=P(Cl)(Cl)[Cl:16].[NH4+].[OH-]>C(Cl)(Cl)Cl>[Cl:16][C:8]1[N:7]=[C:6]2[N:13]=[C:3]([CH2:1][CH3:2])[NH:4][C:5]2=[C:10]([CH3:11])[CH:9]=1

Participants

5

Reactant 3

HCID 14923Ammonium HydroxideHCID 24813Phosphorus oxychlorideHCID 178437532HCID 178437532, compound

Product 1

HCID 193857345-chloro-2-ethyl-7-methyl-3H-Imidazo[4,5-b]pyridine

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 2-ethyl-7-methylimidazo[4,5-b]pyridine (28 g, 174 mmol) and m-chloroperbenzoic acid (80-90%, 44.6 g) in CHCl3 (300 mL) was heated at reflux for 0.5 hours. The mixture was concentrated and purified (SiO2, 100% CH2Cl2 gradient to 30% CH2Cl2 /MeOH) to give 29.8 g of 2-ethyl-7-methylimidazo[4,5-b]pyridine-4-oxide as a solid. 1H NMR (300 MHz, CD3OD) δ8.13 (d, 1H, J=6 Hz), 7.13 (d, 1H, J=6 Hz), 3.01 (q, 2H, J=7.5 Hz), 2.60 (s, 3H), 1.46 (t, 3H, J=7.5 Hz). A mixture of the N-oxide (29.75 g, 0.168 mol), CHCl3 (25 mL) and POCl3 (160 mL) was heated to 80° C. for 1 hours. After pouring over ice, the mixture was neutralized by careful addition of NH4OH and extracted with EtOAc. Concentration gave 23.8 g of 5-chloro-2-ethyl-7-methylimidazo[4,5-b]pyridine as a solid. 1H NMR (250 MHz, CDCl3) δ7.07 (s, 1H) 3.10 (q, 2H, J=7.5 Hz), 2.67 (s, 3H), 1.48 (t, 3H, J=7.5 Hz).

Workup

  1. additionAfter pouring over ice
  2. extractionextracted with EtOAc
  3. concentrationConcentration

Sources & evidence

ORD record
ord-416026de90a0467cb2f64845a46fb3c2
Source dataset
uspto-grants-1992_04
Patent number
US05102880

Reaction notes

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