Ethanol → 2-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)-5-(2-methylprop-1-en-1-yl)pyridine

HRID 1882040Notes

Reaction equation

HRID 1882040 reaction equation
[CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([CH2:18][CH:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)[C:14](=O)[CH:15]=[CH2:16])=[CH:9][CH:8]=2)(=[O:6])=[O:5])[CH2:3][CH2:2]1.O1CCCC1.C(O)C.[CH3:33][C:34]([CH3:44])=[CH:35][C:36]1[CH:37]=[CH:38][C:39]([CH:42]=O)=[N:40][CH:41]=1.C([N:47](CC)CC)C>[Cl-].C([N+]1C(C)=C(CCO)SC=1)C1C=CC=CC=1.O>[CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([C:14]3[NH:47][C:42]([C:39]4[CH:38]=[CH:37][C:36]([CH:35]=[C:34]([CH3:44])[CH3:33])=[CH:41][N:40]=4)=[CH:16][CH:15]=3)[CH2:18][CH:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)=[CH:9][CH:8]=2)(=[O:5])=[O:6])[CH2:2][CH2:3]1

Participants

8

Reactant 5

HCID 702EthanolHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 469414365-(2-Methylprop-1-en-1-yl)pyridine-2-carbaldehydeHCID 593312584-[4-(cyclopropylsulfonyl)phenyl]-5-(tetrahydro-2H-pyran-4-yl)pent-1-en-3-one

Product 1

HCID 593315182-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)-5-(2-methylprop-1-en-1-yl)pyridineYield 80%

Reagents, catalysts & solvents 2

HCID 28333523-Benzyl-5-(2-hydroxyethyl)-4-methylthiazolium chlorideCatalystHCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 4-[4-(cyclopropylsulfonyl)phenyl]-5-(tetrahydro-2H-pyran-4-yl)pent-1-en-3-one (1.20 g) in a mixed solvent of tetrahydrofuran (15 mL) and ethanol (15 mL) was deaerated, 5-(2-methylprop-1-en-1-yl)pyridine-2-carbaldehyde (0.666 g), 3-benzyl-5-(2-hydroxyethyl)-4-methyl-1,3-thiazol-3-ium chloride (93 mg) and triethylamine (0.192 mL) were added, and the mixture was stirred at 70° C. for 1.5 hr under a nitrogen atmosphere. 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 magnesium sulfate and concentrated under reduced pressure. To a solution of the residue in acetic acid (50 mL) was added ammonium acetate (2.65 g), and the mixture was stirred at 110° C. for 2 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 sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=10:90-60:40, volume ratio) and recrystallized from hexane-ethyl acetate to give the title compound (1.35 g, yield 80%) as colorless crystals. MS: 491 (MH+). melting point 114-116° C.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed successively with water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. additionTo a solution of the residue in acetic acid (50 mL) was added ammonium acetate (2.65 g)
  6. stirringthe mixture was stirred at 110° C. for 2 hr
  7. extractionextracted with ethyl acetate
  8. washThe extract was washed successively with water and saturated brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=10:90-60:40, volume ratio)
  12. customrecrystallized from hexane-ethyl acetate

Sources & evidence

ORD record
ord-ffc39a62164d4cf68654f4e72c3a2d1e
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

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