Chloroacetone → HCID 59228757, compound

HRID 2284617Notes

Reaction equation

HRID 2284617 reaction equation
Cl[CH2:2][C:3](=O)[CH3:4].[NH2:6][C:7]1[CH:12]=[CH:11][C:10]([I:13])=[CH:9][N:8]=1>CCO>[I:13][C:10]1[CH:11]=[CH:12][C:7]2[N:8]([CH:2]=[C:3]([CH3:4])[N:6]=2)[CH:9]=1

Participants

4

Reactant 2

HCID 6571Chloroacetone2×HCID 885792-Pyridinamine, 5-iodo-2×

Product 1

HCID 59228757HCID 59228757, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Chloroacetone (3 mL) was added to a stirring solution of 2-amino-5-iodopyridine (2g) in EtOH (20 mL) and heated to reflux. The reaction progress (50% of unreacted 2-amino-5-iodopyridine) was analyzed after 12 h by LC/MS and TLC. Additional amount of chloroacetone (3 mL) was transferred to the reaction mixture and heated for additional 8 h to observe the >90% consumption of 2-amino-5-iodopyridine. The reaction mixture was cooled and concentrated to dryness. The crude residue was diluted with EtOAc (130 mL)/water (50 mL) and neutralized with 5% aq. NaOH (25 mL). Organic layer from the biphasic solution was separated and the aqueous phase was partitioned again with EtOAc (70 mL). Combined organic layers were dried over MgSO4, filtered and concentrated. The crude brown residue was purified by Combiflash® companion System® with RediSep® silica gel column [(80g), 50-75-100% EtOAC/hexanes as an eluting solvent gradient. The product fractions were concentrated to provide 2.2 g of 6-iodo-2-methylimidazo[1,2-a]pyridine (1.8 g) as an off-brown solid. 1H NMR (300 MHz, DMSO-d6) δ 8.81 (dd, J=1.7, 1.0 Hz, 1H), 7.62-7.55 (app s, 1H), 7.31 (dd, J=9.4, 1.7 Hz, 1H), 7.25 (dd, J=9.3, 0.8 Hz, 1H), 2.29 (s, 3H). See Helvetica Chimica Acta, 90(12), 2349-2367 (2007).

Workup

  1. temperatureheated to reflux
  2. temperatureheated for additional 8 h
  3. customthe >90% consumption of 2-amino-5-iodopyridine
  4. temperatureThe reaction mixture was cooled
  5. concentrationconcentrated to dryness
  6. additionThe crude residue was diluted with EtOAc (130 mL)/water (50 mL)
  7. customOrganic layer from the biphasic solution was separated
  8. customthe aqueous phase was partitioned again with EtOAc (70 mL)
  9. dry with materialCombined organic layers were dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude brown residue was purified by Combiflash® companion System® with RediSep® silica gel column [(80g), 50-75-100% EtOAC/hexanes as an eluting solvent gradient
  13. concentrationThe product fractions were concentrated

Sources & evidence

ORD record
ord-436e8185bad048dbb5b89ff0473bf470
Source dataset
uspto-grants-2015_09
Patent number
US09145433B2

Reaction notes

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