Glyoxal → 2-chloro-6-(1H-imidazol-2-yl)pyridine

HRID 916664Notes

Reaction equation

HRID 916664 reaction equation
C(C=O)=O.[OH-].[NH4+:6].[Cl:7][C:8]1[N:13]=[C:12]([CH:14]=O)[CH:11]=[CH:10][CH:9]=1.ClC1C=CC=[C:19]([CH3:23])[N:18]=1>CO>[Cl:7][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]([C:14]2[NH:6][CH:23]=[CH:19][N:18]=2)[N:13]=1

Participants

6

Reactant 4

HCID 7860GlyoxalHCID 14923Ammonium HydroxideHCID 876016-Chloro-2-picolineHCID 107968486-Chloro-2-pyridinecarboxaldehyde

Product 1

HCID 575033132-chloro-6-(1H-imidazol-2-yl)pyridine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Glyoxal (40% w/w H2O, 20 mL) and ammonium hydroxide (con. 40 mL) are added to a solution of 6-chloro-pyridine-2-carbaldehyde (0.127 mol; prepared from 2-chloro-6-methyl-pyridine essentially as described by Vacher et al. (1998) J. Med. Chem. 41:5080) in MeOH (620 mL) at 0° C. The mixture is allowed to warm gradually to room temperature over an 18 hour period. The solvent is removed. Water (125 mL) is added to the residue and the mixture is extracted with methylene chloride (5×150 mL). The combined organic layers are washed with brine (2×100 mL), dried and solvent removed. The crude product is triturated with ethyl ether (200 mL) to give 2-chloro-6-(1H-imidazol-2-yl)-pyridine as a solid.

Workup

  1. customat 0° C
  2. customThe solvent is removed
  3. additionWater (125 mL) is added to the residue
  4. extractionthe mixture is extracted with methylene chloride (5×150 mL)
  5. washThe combined organic layers are washed with brine (2×100 mL)
  6. customdried
  7. customsolvent removed
  8. customThe crude product is triturated with ethyl ether (200 mL)

Sources & evidence

ORD record
ord-9aa026ce563b4603986456ee72cd8715
Source dataset
uspto-grants-2007_09
Patent number
US07271170B2

Reaction notes

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