Sodium Iodide → HCID 66778303, compound

HRID 2090982Notes

Reaction equation

HRID 2090982 reaction equation
Cl[CH:2]([CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([CH3:12])[N:4]=1.[NH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([N:28]([CH3:36])[CH2:29][CH2:30][C:31]([O:33]CC)=[O:32])=[O:27])=[CH:22][CH:21]=1.[I-].[Na+].C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[NH4+].[OH-].[Na+]>C(O)C.O1CCCC1.CN(C)C(=O)C>[CH:13]1([CH:2]([NH:19][C:20]2[CH:21]=[CH:22][C:23]([C:26]([N:28]([CH3:36])[CH2:29][CH2:30][C:31]([OH:33])=[O:32])=[O:27])=[CH:24][CH:25]=2)[C:3]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]([CH3:12])[N:4]=2)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

10

Reactant 6

HCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 46941342Ethyl 3-{[(4-aminophenyl)carbonyl](methyl)amino}propanoateHCID 66778490HCID 66778490, compound

Product 1

HCID 66778303HCID 66778303, compoundYield 45%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 3-[chloro(cyclohexyl)methyl]-1-methyl-1H-indazole (465 mg) synthesized above, ethyl 3-{[(4-aminophenyl)carbonyl](methyl)amino}propanoate (531 mg) synthesized in Example 2(2), sodium iodide (531 mg) and N,N-dimethylacetamide (10 mL) was added sodium carbonate (375 mg), and the mixture was stirred under argon atmosphere at 100° 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 column chromatography (ethyl acetate:hexane=3:2, volume ratio) to give a white solid. To a mixture of the obtained solid, tetrahydrofuran (5 mL) and ethanol (5 mL) was added 1N aqueous sodium hydroxide solution (2.00 mL), and the mixture was stirred at room temperature for 3 hr. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in water (10 mL), and 1N hydrochloric acid (2.00 mL) was added at 0° C. The resulting precipitate was collected by filtration to give the title object compound (356 mg, 45%) 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 column chromatography (ethyl acetate:hexane=3:2, volume ratio)
  8. customto give a white solid
  9. stirringthe mixture was stirred at room temperature for 3 hr
  10. concentrationThe reaction mixture was concentrated under reduced pressure
  11. dissolutionthe residue was dissolved in water (10 mL)
  12. addition1N hydrochloric acid (2.00 mL) was added at 0° C
  13. filtrationThe resulting precipitate was collected by filtration

Sources & evidence

ORD record
ord-70e1924bc8364445a7b5587037f9cec8
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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