Sodium Iodide → HCID 68513423, compound

HRID 1877288Notes

Reaction equation

HRID 1877288 reaction equation
[CH:1]1([CH:7]([C:9]2[CH:13]=[C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[S:11][C:10]=2[CH3:20])O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:21][C:22]1[CH:23]=[CH:24][C:25]([C:28]([O:30]C)=[O:29])=[N:26][CH:27]=1.[I-].[Na+].C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[NH4+].[OH-].[Na+]>C(O)C.O1CCCC1.CN(C)C=O>[CH:1]1([CH:7]([NH:21][C:22]2[CH:23]=[CH:24][C:25]([C:28]([OH:30])=[O:29])=[N:26][CH:27]=2)[C:9]2[CH:13]=[C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[S:11][C:10]=2[CH3:20])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

10

Reactant 6

HCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 12457877Methyl 5-aminopyridine-2-carboxylateHCID 68511971HCID 68511971, compound

Product 1

HCID 68513423HCID 68513423, compoundYield 29.2%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 3-[chloro(cyclohexyl)methyl]-2-methyl-5-phenylthiophene (909 mg) synthesized in Example 278 (6), methyl 5-amino-pyridine-2-carboxylate (438 mg), sodium iodide (863 mg) and N,N-dimethylformamide (10 mL) was added sodium carbonate (611 mg), and the mixture was stirred at 80° C. overnight. Saturated aqueous ammonium chloride solution was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (30-70% ethyl acetate/hexane) to give a pale-brown oil. To a mixture of the obtained oil, tetrahydrofuran (10 mL) and ethanol (10 mL) was added 1N aqueous sodium hydroxide solution (10 mL), and the mixture was stirred with heating under reflux overnight. The reaction mixture was concentrated under reduced pressure. 1N Hydrochloric acid (10 mL) was added to the residue, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was washed with diisopropyl ether to give the title compound (342 mg, 29%) as a white solid.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (30-70% ethyl acetate/hexane)
  8. customto give a pale-brown oil
  9. stirringthe mixture was stirred
  10. temperaturewith heating
  11. temperatureunder reflux overnight
  12. concentrationThe reaction mixture was concentrated under reduced pressure
  13. addition1N Hydrochloric acid (10 mL) was added to the residue
  14. extractionthe mixture was extracted with ethyl acetate
  15. washThe extract was washed with saturated brine
  16. dry with materialdried over magnesium sulfate
  17. concentrationconcentrated under reduced pressure
  18. washThe residue was washed with diisopropyl ether

Sources & evidence

ORD record
ord-aada0f60110b4b59875a9d62811e655a
Source dataset
uspto-grants-2012_11
Patent number
US08309580B2

Reaction notes

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