Chloroacetaldehyde → 6-Bromoimidazo[1,2-a]pyridine-7-carbonitrile

HRID 420491Notes

Reaction equation

HRID 420491 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:7]([Br:10])=[CH:8][N:9]=1)[C:5]#[N:6].C([O-])(O)=O.[Na+].Cl[CH2:17][CH:18]=O>CCO>[Br:10][C:7]1[C:4]([C:5]#[N:6])=[CH:3][C:2]2[N:9]([CH:17]=[CH:18][N:1]=2)[CH:8]=1

Participants

5

Reactant 3

HCID 33ChloroacetaldehydeHCID 516892Sodium BicarbonateHCID 534405772-Amino-5-bromopyridine-4-carbonitrile

Product 1

HCID 666589436-Bromoimidazo[1,2-a]pyridine-7-carbonitrileYield 53%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 2-amino-5-bromo-isonicotinonitrile (5.0 g, 25.3 mmol), NaHCO3 (3.6 g, 42.9 mmol) and chloracetaldehyde (17.0 mL, 114.0 mmol) in EtOH (160 mL) was vigorously stirred and refluxed for 14 h. The reaction mixture was cooled to RT, concentrated under vacuum and the remaining residue was suspended in DCM (500 mL) and brine (100 mL). The aqueous layer was separated and extracted with DCM (5×), and the combined organic fractions were dried over Na2SO4, filtered, and evaporated. The residue was purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, [hexane/DCM 1:1]/TBME 95:5→3:7) to yield the title compound (2.97 g, 13.4 mmol, 53%) as an orange solid. MS: 223 [M+1]+; HPLC: AtRet=0.54; TLC: RF 0.17 (hexane/DCM/TBME 1:1:2).

Workup

  1. temperaturerefluxed for 14 h
  2. concentrationconcentrated under vacuum
  3. customThe aqueous layer was separated
  4. extractionextracted with DCM (5×)
  5. dry with materialthe combined organic fractions were dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, [hexane/DCM 1:1]/TBME 95:5→3:7)

Sources & evidence

ORD record
ord-d4758aa1e7db481ab68d4e7ff6ca2fe3
Source dataset
uspto-grants-2012_01
Patent number
US08097617B2

Reaction notes

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