2-Pyridinecarboxaldehyde → 2-(5-{1-[4-(ethylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)pyridine

HRID 1882025Notes

Reaction equation

HRID 1882025 reaction equation
[CH2:1]([S:3]([C:6]1[CH:11]=[CH:10][C:9]([CH:12]([CH2:17][CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[C:13](=O)[CH:14]=[CH2:15])=[CH:8][CH:7]=1)(=[O:5])=[O:4])[CH3:2].[N:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[CH:30]=O.C([O-])(=O)C.[NH4+:36].C(=O)([O-])O.[Na+]>C(O)C.[Cl-].C([N+]1C(C)=C(CCO)SC=1)C1C=CC=CC=1.C(O)(=O)C.O.C(N(CC)CC)C>[CH2:1]([S:3]([C:6]1[CH:11]=[CH:10][C:9]([CH:12]([C:13]2[NH:36][C:30]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][N:24]=3)=[CH:15][CH:14]=2)[CH2:17][CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[CH:8][CH:7]=1)(=[O:5])=[O:4])[CH3:2]

Participants

10

Reactant 4

HCID 142732-PyridinecarboxaldehydeHCID 516892Sodium BicarbonateHCID 517165Ammonium AcetateHCID 593315624-[4-(ethylsulfonyl)phenyl]-5-(tetrahydro-2H-pyran-4-yl)pent-1-en-3-one

Product 1

HCID 593314502-(5-{1-[4-(ethylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)pyridineYield 69%

Reagents, catalysts & solvents 5

HCID 28333523-Benzyl-5-(2-hydroxyethyl)-4-methylthiazolium chlorideCatalystHCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 962WaterSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 4-[4-(ethylsulfonyl)phenyl]-5-(tetrahydro-2H-pyran-4-yl)pent-1-en-3-one (0.409 g) in ethanol (15 mL) were added pyridine-2-carbaldehyde (0.139 mL), 3-benzyl-5-(2-hydroxyethyl)-4-methyl-1,3-thiazol-3-ium chloride (36 mg) and triethylamine (0.073 mL), and the mixture was heated under reflux for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under m reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=30:70-80:20, volume ratio) to give a colorless oil. To a solution of the obtained oil in acetic acid (10 mL) was added ammonium acetate (356 mg), and the mixture was stirred at 110° C. for 3 hr. The reaction mixture was neutralized with saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=10:90-80:20, volume ratio) to give the title compound (0.350 g, yield 69%) as a colorless amorphous solid. MS: 425 (MH+).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 1 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed successively with water and saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under m reduced pressure
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=30:70-80:20, volume ratio)
  8. customto give a colorless oil
  9. extractionextracted with ethyl acetate
  10. washThe extract was washed successively with water and saturated brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=10:90-80:20, volume ratio)

Sources & evidence

ORD record
ord-4f88b531d6bf401aa5fd5852d94dc1b5
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

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