Tetrahydrofuran → methyl [6-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)pyridin-3-yl]acetate

HRID 1882113Notes

Reaction equation

HRID 1882113 reaction equation
[CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([C:21]3[NH:25][C:24]([C:26]4[N:31]=[CH:30][C:29](C=O)=[CH:28][CH:27]=4)=[CH:23][CH:22]=3)[CH2:14][CH:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[CH:9][CH:8]=2)(=[O:6])=[O:5])[CH2:3][CH2:2]1.CS(CSC)=O.C[OH:41].[OH-].C([N+](C)(C)C)C1C=CC=CC=1.[O:54]1[CH2:58]C[CH2:56][CH2:55]1>O>[CH:1]1([S:4]([C:7]2[CH:8]=[CH:9][C:10]([CH:13]([C:21]3[NH:25][C:24]([C:26]4[N:31]=[CH:30][C:29]([CH2:56][C:55]([O:54][CH3:58])=[O:41])=[CH:28][CH:27]=4)=[CH:23][CH:22]=3)[CH2:14][CH:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[CH:11][CH:12]=2)(=[O:6])=[O:5])[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 99129Methyl (methylsulfinyl)methyl sulfideHCID 19865511Benzyltrimethylammonium hydroxide methanolHCID 593314196-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)pyridine-3-carbaldehyde

Product 1

HCID 59331493methyl [6-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)pyridin-3-yl]acetateYield 64%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 6-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)pyridine-3-carbaldehyde (3.0 g), methyl (methylsulfinyl)methyl sulfide (2.43 g), 40% benzyltrimethylammonium hydroxide methanol solution (5 mL), and tetrahydrofuran (50 mL) was heated under reflux for 24 hr. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. A mixture of the residue and 10% hydrogen chloride methanol solution (60 mL) was heated under reflux for 15 hr, and cooled to room temperature. To the reaction mixture was basified with saturated aqueous sodium hydrogen carbonate and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and the title compound (2.02 g, yield 64%) was obtained as a brown amorphous solid from a fraction eluted with ethyl acetate-hexane (1:1-2:1, volume ratio). MS: 509 (MH+).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 24 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe ethyl acetate layer was washed with saturated brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. additionA mixture of the residue and 10% hydrogen chloride methanol solution (60 mL)
  8. temperaturewas heated
  9. temperatureunder reflux for 15 hr
  10. extractionthe mixture was extracted with ethyl acetate
  11. washThe ethyl acetate layer was washed with saturated brine
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-32e0a338ff1548c3acd23052f269e7a7
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

Loading…