Water → 1-[6-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)pyridin-3-yl]-2-(methylsulfonyl)ethanol

HRID 1882112Notes

Reaction equation

HRID 1882112 reaction equation
[CH3:1][S:2]([CH3:5])(=[O:4])=[O:3].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[CH:16]1([S:19]([C:22]2[CH:27]=[CH:26][C:25]([CH:28]([C:36]3[NH:40][C:39]([C:41]4[N:46]=[CH:45][C:44]([CH:47]=[O:48])=[CH:43][CH:42]=4)=[CH:38][CH:37]=3)[CH2:29][CH:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)=[CH:24][CH:23]=2)(=[O:21])=[O:20])[CH2:18][CH2:17]1.O>O1CCCC1>[CH:16]1([S:19]([C:22]2[CH:23]=[CH:24][C:25]([CH:28]([C:36]3[NH:40][C:39]([C:41]4[N:46]=[CH:45][C:44]([CH:47]([OH:48])[CH2:1][S:2]([CH3:5])(=[O:4])=[O:3])=[CH:43][CH:42]=4)=[CH:38][CH:37]=3)[CH2:29][CH:30]3[CH2:31][CH2:32][O:33][CH2:34][CH2:35]3)=[CH:26][CH:27]=2)(=[O:21])=[O:20])[CH2:18][CH2:17]1

Participants

6

Reactant 4

HCID 962WaterHCID 6213Dimethyl SulfoneHCID 2733832Lithium HexamethyldisilazideHCID 593314196-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)pyridine-3-carbaldehyde

Product 1

HCID 593314871-[6-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)pyridin-3-yl]-2-(methylsulfonyl)ethanolYield 22.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of dimethylsulfone (446 mg) in tetrahydrofuran (10 mL) was added dropwise lithium hexamethyldisilazide (1.6M tetrahydrofuran solution) (2.7 mL) at −78° C., and the mixture was stirred for 1 hr. To the reaction mixture was added dropwise a solution of 6-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)pyridine-3-carbaldehyde (1 g) in tetrahydrofuran (5 mL), and the mixture was stirred for 1 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. The residue was subjected to silica gel column chromatography to give a pale-yellow amorphous solid from a fraction eluted with ethyl acetate-methanol (9:1, volume ratio). The obtained pale-yellow amorphous solid was subjected to basic silica gel column chromatography to give a pale-yellow amorphous solid from a fraction eluted with ethyl acetate-methanol (9:1, volume ratio). The pale-yellow amorphous solid was purified by preparative HPLC to give the title compound (270 mg, yield 22%) as a colorless amorphous solid. MS: 559 (MH+).

Workup

  1. stirringthe mixture was stirred for 1 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe ethyl acetate layer was washed with saturated brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customto give a pale-yellow amorphous solid from a fraction
  7. washeluted with ethyl acetate-methanol (9:1, volume ratio)
  8. customto give a pale-yellow amorphous solid from a fraction
  9. washeluted with ethyl acetate-methanol (9:1, volume ratio)
  10. customThe pale-yellow amorphous solid was purified by preparative HPLC

Sources & evidence

ORD record
ord-207d98ac9c5342cea3419d250ebe318e
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

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