Methanol → HCID 57899331, compound

HRID 425753Notes

Reaction equation

HRID 425753 reaction equation
[CH:1]1([NH:4][C:5]2[CH2:9][O:8][C:7](=[O:10])[CH:6]=2)[CH2:3][CH2:2]1.[H-].[Na+].Br[CH2:14][C:15]1[CH:16]=[N:17][C:18]([Cl:22])=[C:19]([I:21])[CH:20]=1.CO>O1CCCC1>[Cl:22][C:18]1[N:17]=[CH:16][C:15]([CH2:14][N:4]([CH:1]2[CH2:3][CH2:2]2)[C:5]2[CH2:9][O:8][C:7](=[O:10])[CH:6]=2)=[CH:20][C:19]=1[I:21]

Participants

6

Reactant 4

HCID 887MethanolHCID 24758Sodium hydrideHCID 55300443HCID 55300443, compoundHCID 57899326HCID 57899326, compound

Product 1

HCID 57899331HCID 57899331, compoundYield 26.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

200 mg (1.44 mmol) of 4-(cyclopropylamino)furan-2(5H)-one (VI-1) and 86 mg (2.17 mmol) of a 60% strength dispersion of sodium hydride in mineral oil in 100 ml of tetrahydrofuran are heated under reflux for 1 hour. After cooling to room temperature, 478 mg (1.44 mmol) of 3-bromomethyl-6-chloro-5-iodopyridine (VII-3) are added, and the mixture is heated under reflux for a further 6 hours. After cooling of the reaction mixture to room temperature and addition of methanol, the mixture is concentrated under reduced pressure. The residue is taken up in ethyl acetate and the mixture is washed successively twice with 1 N aqueous hydrochloric acid, twice with 1 N aqueous sodium hydroxide solution and saturated sodium chloride solution and dried over sodium sulphate. Concentration of the organic phase under reduced pressure and purification of the residue by column chromatography on silica gel (silica gel 60-Merck, particle size: 0.04 to 0.063 mm) using the mobile phase mixture ethyl acetate:cyclohexane (3:1) gives 149 mg (26% of theory) of 4-[[(6-chloro-5-iodopyridin-3-yl)methyl](cyclopropyl)amino]furan-2(5H)-one.

Workup

  1. temperatureunder reflux for 1 hour
  2. temperaturethe mixture is heated
  3. temperatureunder reflux for a further 6 hours
  4. temperatureAfter cooling of the reaction mixture to room temperature
  5. concentrationthe mixture is concentrated under reduced pressure
  6. washthe mixture is washed successively twice with 1 N aqueous hydrochloric acid, twice with 1 N aqueous sodium hydroxide solution and saturated sodium chloride solution
  7. dry with materialdried over sodium sulphate
  8. customConcentration of the organic phase under reduced pressure and purification of the residue by column chromatography on silica gel (silica gel 60-Merck, particle size: 0.04 to 0.063 mm)

Sources & evidence

ORD record
ord-beff6fb7ca734cae961e883e871e0e34
Source dataset
uspto-grants-2012_01
Patent number
US08106212B2

Reaction notes

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