Tetrahydrofuran → 1-{[2-(5-{1-[4-(Cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2h-pyran-4-yl)ethyl}-1h-pyrrol-2-yl)-1,3-thiazol-5-yl]methyl}piperidin-4-one hydrochloride

HRID 1882056Notes

Reaction equation

HRID 1882056 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[S:27][C:28](CO)=[CH:29][N:30]=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.S(Cl)([Cl:35])=O.[O:37]1[CH2:41][CH2:40][CH2:39]C1>CN(C)C=O>[ClH:35].[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[S:27][C:28]([CH2:21][N:25]5[CH2:24][CH2:23][C:41](=[O:37])[CH2:40][CH2:39]5)=[CH:29][N:30]=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

5

Reactant 3

HCID 8028TetrahydrofuranHCID 24386Thionyl ChlorideHCID 59331583[2-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)-1,3-thiazol-5-yl]methanol

Product 1

HCID 684312441-{[2-(5-{1-[4-(Cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2h-pyran-4-yl)ethyl}-1h-pyrrol-2-yl)-1,3-thiazol-5-yl]methyl}piperidin-4-one hydrochlorideYield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideCatalyst

Conditions

Temperature
0 °C

Procedure

To a mixture of [2-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)-1,3-thiazol-5-yl]methanol (0.30 g), N,N-dimethylformamide (two drops) and tetrahydrofuran (6 mL) was added thionyl chloride (0.09 mL) at 0° C. The reaction mixture was stirred at 0° C. for 1 hr and concentrated. The obtained residue was dissolved in tetrahydrofuran (2 mL) and the solution was added to a mixture of piperidine-4,4-diol hydrochloride (0.19 g), potassium carbonate (0.17 g) and N,N-dimethylformamide (6 mL) at 0° C. The reaction mixture was stirred at room temperature overnight, water was added, 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 basic silica gel column chromatography to give a yellow amorphous solid from a fraction eluted with tetrahydrofuran-hexane (3:1, volume ratio). The obtained amorphous solid was dissolved in ethyl acetate, and 4M hydrogen chloride-ethyl acetate solution (1.0 mL) was added. The precipitated crystals were collected by filtration, and dried to give the title compound (0.21 g, yield 57%) as yellow crystals. melting point 146-148° C. MS: 554 (MH+).

Workup

  1. concentrationconcentrated
  2. dissolutionThe obtained residue was dissolved in tetrahydrofuran (2 mL)
  3. additionthe solution was added to a mixture of piperidine-4,4-diol hydrochloride (0.19 g), potassium carbonate (0.17 g) and N,N-dimethylformamide (6 mL) at 0° C
  4. stirringThe reaction mixture was stirred at room temperature overnight
  5. additionwater was added
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe ethyl acetate layer was washed with saturated brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customto give a yellow amorphous solid from a fraction
  11. washeluted with tetrahydrofuran-hexane (3:1, volume ratio)
  12. dissolutionThe obtained amorphous solid was dissolved in ethyl acetate
  13. addition4M hydrogen chloride-ethyl acetate solution (1.0 mL) was added
  14. filtrationThe precipitated crystals were collected by filtration
  15. customdried

Sources & evidence

ORD record
ord-4afecf4946fb4deb945e45a841916e7e
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

Loading…