Dihydro-3(2H)-thiophenone → 3-(5-(5-chloro-2-(1-methyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)tetrahydrothiophen-3-ol

HRID 2362744Notes

Reaction equation

HRID 2362744 reaction equation
[Cl:1][C:2]1[C:3]([C:27]2[S:31][CH:30]=[N:29][CH:28]=2)=[C:4]2[CH:10]=[C:9]([C:11]3[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=3)[N:8]([S:17]([C:20]3[CH:26]=[CH:25][C:23]([CH3:24])=[CH:22][CH:21]=3)(=[O:19])=[O:18])[C:5]2=[N:6][CH:7]=1.C([Li])CCC.[S:37]1[CH2:41][CH2:40][C:39](=[O:42])[CH2:38]1>O1CCCC1>[Cl:1][C:2]1[C:3]([C:27]2[S:31][C:30]([C:39]3([OH:42])[CH2:40][CH2:41][S:37][CH2:38]3)=[N:29][CH:28]=2)=[C:4]2[CH:10]=[C:9]([C:11]3[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=3)[N:8]([S:17]([C:20]3[CH:21]=[CH:22][C:23]([CH3:24])=[CH:25][CH:26]=3)(=[O:19])=[O:18])[C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 61252Dihydro-3(2H)-thiophenoneHCID 670035295-(5-chloro-2-(1-methyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazoleHCID 178418339Butyllithium

Product 1

HCID 670029113-(5-(5-chloro-2-(1-methyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)tetrahydrothiophen-3-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of Example 144A (0.095 g, 0.202 mmol) in tetrahydrofuran (2.5 mL) was cooled to −78° C. and treated with n-butyllithium (2.45 M in hexanes, 0.173 mL, 0.424 mmol) dropwise over 5 minutes. The reaction was stirred at −78° C. for 20 minutes, and dihydrothiophen-3(2H)-one (0.033 mL, 0.384 mmol) was added. The reaction was stirred 60 minutes at −78° C. and was quenched by addition of saturated aqueous sodium bicarbonate solution. The mixture was allowed to warm to ambient temperature and was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by flash chromatography on a silica gel column, eluting with 1% methanol in dichloromethane, to provide the title compound. MS ESI(+) m/z 572.3 [M+H]+.

Workup

  1. stirringThe reaction was stirred 60 minutes at −78° C.
  2. customwas quenched by addition of saturated aqueous sodium bicarbonate solution
  3. temperatureto warm to ambient temperature
  4. extractionwas extracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe concentrate was purified by flash chromatography on a silica gel column
  10. washeluting with 1% methanol in dichloromethane

Sources & evidence

ORD record
ord-59e4be98a1ab43b8b0cb99f5dd7a6f13
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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