Chloroacetaldehyde → Imidazo(1,2-a)pyridine-7-carbonitrile

HRID 1894187Notes

Reaction equation

HRID 1894187 reaction equation
Cl[CH2:2][CH:3]=O.[NH2:5][C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][N:13]=1)[C:9]#[N:10].C([O-])(O)=O.[Na+]>C(O)C>[N:5]1[CH:2]=[CH:3][N:13]2[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[CH:7][C:6]=12

Participants

5

Reactant 3

HCID 33ChloroacetaldehydeHCID 516892Sodium BicarbonateHCID 70155242-Aminoisonicotinonitrile

Product 1

HCID 55267408Imidazo(1,2-a)pyridine-7-carbonitrile

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

Chloroacetaldehyde (˜50% in H2O, 3.24 ml, 26 mmol) was added to a stirred mixture of 2-amino-isonicotinonitrile (1.6 g, 3.4 mmol) and NaHCO3 (2.23 g, 26.5 mmol) in ethanol (20 ml) at RT under N2. The reaction was stirred and heated at 80° C. for 18 hours. After cooling to RT the volatiles were removed in vacuo and the residue was partitioned between EtOAc/H2O. This mixture was filtered to remove some dark insoluble residue. The solid was washed with MeOH. The aqueous layer was extracted with EtOAc (×2). The combined EtOAc extracts were dried (Na2SO4) and filtered. The MeOH washings were added and the volatiles were removed in vacuo. The residue was purified by chromatography on silica: 100% DCM→1% 2M NH3-MeOH/DCM to give the title product. 1H NMR (400 MHz, DMSO-d6): 8.74 (1H, dd), 8.35 (1H, s), 8.19 (1H, s), 7.86 (1H, s), 7.21 (1H, dd).

Workup

  1. temperatureAfter cooling to RT the volatiles
  2. customwere removed in vacuo
  3. customthe residue was partitioned between EtOAc/H2O
  4. filtrationThis mixture was filtered
  5. customto remove some dark insoluble residue
  6. washThe solid was washed with MeOH
  7. extractionThe aqueous layer was extracted with EtOAc (×2)
  8. dry with materialThe combined EtOAc extracts were dried (Na2SO4)
  9. filtrationfiltered
  10. additionThe MeOH washings were added
  11. customthe volatiles were removed in vacuo
  12. customThe residue was purified by chromatography on silica

Sources & evidence

ORD record
ord-f4f939c84e084448a392ef26388af511
Source dataset
uspto-grants-2013_08
Patent number
US08513276B2

Reaction notes

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