Diisopropylamine → HCID 67228832, compound

HRID 1515616Notes

Reaction equation

HRID 1515616 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([O:19][CH3:20])[CH:18]=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([N-][CH:25]([CH3:27])[CH3:26])(C)C.[Li+].[CH2:29]([Li])[CH2:30][CH2:31]C.CCCCCC.C(NC(C)C)(C)C.[CH:47]1([CH:53]=[O:54])CCCCC1>O1CCCC1>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([O:19][CH3:20])[CH:18]=[C:13]3[CH:12]=[C:11]2[CH:53]([OH:54])[CH2:47][CH:26]2[CH2:25][CH2:27][CH2:29][CH2:30][CH2:31]2)(=[O:8])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

8

Reactant 6

HCID 7912DiisopropylamineHCID 8058HexaneHCID 16275CyclohexanecarboxaldehydeHCID 2724682Lithium diisopropylamideHCID 222736501H-Pyrrolo[2,3-B]pyridine, 5-methoxy-1-(phenylsulfonyl)-HCID 178418339Butyllithium

Product 1

HCID 67228832HCID 67228832, compoundYield 37.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a suspension of 1-benzenesulfonyl-5-methoxy-1H-pyrrolo[2,3-b]pyridine (0.45 g, 1.56 mmol) in dry tetrahydrofuran (20 mL) at −78° C. was added freshly prepared lithium diisopropylamide [prepared by adding 1.6 M n-butyllithium in n-hexane (1.5 mL, 2.34 mmol) to a 0° C. solution of diisopropylamine (0.35 mL, 2.48 mmol) in dry tetrahydrofuran (10 mL)] dropwise. The mixture was stirred at −78° C. for 5 min and then treated with cyclohexanecarbaldehyde (353.8 mg, 2.81 mmol) dropwise. The resulting mixture was stirred at −78° C. for 1 h and then quenched with brine. The mixture was extracted with ethyl acetate (2×200 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 20% ethyl acetate/hexanes) afforded 1-(1-benzenesulfonyl-5-methoxy-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-cyclohexyl-ethanol (240 mg, 37.2%) as a white solid: LC/MS m/e calcd for C22H26N2O4S [M+H]+ 415.53, observed 415.3.

Workup

  1. customprepared
  2. stirringThe resulting mixture was stirred at −78° C. for 1 h
  3. customquenched with brine
  4. extractionThe mixture was extracted with ethyl acetate (2×200 mL)
  5. washwashed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customPurification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-ecefa2120b5c4ea0b9289357266ac1b1
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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