Sodium Iodide → Methyl 5-{[cyclohexyl(5-fluoro-3-methyl-1-benzofuran-2-yl)methyl]amino}pyridine-2-carboxylate

HRID 2091063Notes

Reaction equation

HRID 2091063 reaction equation
[CH:1]1([CH:7]([C:9]2[O:10][C:11]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:12]=3[C:13]=2[CH3:14])O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.S(Cl)(Cl)=O.C(=O)([O-])O.[Na+].[NH2:29][C:30]1[CH:31]=[CH:32][C:33]([C:36]([O:38][CH3:39])=[O:37])=[N:34][CH:35]=1.[I-].[Na+].C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[NH4+]>C1(C)C=CC=CC=1.CN(C)C=O>[CH:1]1([CH:7]([NH:29][C:30]2[CH:31]=[CH:32][C:33]([C:36]([O:38][CH3:39])=[O:37])=[N:34][CH:35]=2)[C:9]2[O:10][C:11]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:12]=3[C:13]=2[CH3:14])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

10

Reactant 7

HCID 5238Sodium IodideHCID 10340Sodium CarbonateHCID 24386Thionyl ChlorideHCID 25517Ammonium ChlorideHCID 516892Sodium BicarbonateHCID 12457877Methyl 5-aminopyridine-2-carboxylateHCID 66777937Cyclohexyl(5-fluoro-3-methyl-1-benzofuran-2-yl)methanol

Product 1

HCID 66777793Methyl 5-{[cyclohexyl(5-fluoro-3-methyl-1-benzofuran-2-yl)methyl]amino}pyridine-2-carboxylateYield 40.1%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution (15 mL) of cyclohexyl(5-fluoro-3-methyl-1-benzofuran-2-yl)methanol (1.50 g) synthesized in Example A37(2) in toluene was added thionyl chloride (625 μL), and the mixture was stirred at room temperature for 3 hr. The reaction mixture was poured into ice-cooled saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to give a brown oil. To a mixture of the obtained oil, methyl 5-aminopyridine-2-carboxylate (957 mg), sodium iodide (1.71 g) and N,N-dimethylformamide (15 mL) was added sodium carbonate (1.21 g), and the mixture was stirred at 80° C. overnight. Saturated aqueous ammonium chloride solution was added to quench the reaction, and the reaction 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 (10-50% ethyl acetate/hexane) to give the title object compound (909 mg, 40%) as a pale-brown solid.

Workup

  1. additionThe reaction mixture was poured into ice-
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customto give a brown oil
  7. stirringthe mixture was stirred at 80° C. overnight
  8. customto quench
  9. customthe reaction
  10. extractionthe reaction mixture was extracted with ethyl acetate
  11. washThe extract was washed with saturated brine
  12. dry with materialdried over magnesium sulfate
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified by silica gel column chromatography (10-50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-c1a73fd95d334af8b51e797ab3ef117d
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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