Diisopropylamine → {1-benzenesulfonyl-2-[1-hydroxy-2-(tetrahydro-pyran-4-yl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-carbamic acid tert-butyl ester

HRID 1515874Notes

Reaction equation

HRID 1515874 reaction equation
[C:1]([O:5][C:6](=[O:26])[NH:7][C:8]1[CH:9]=[C:10]2[CH:16]=[CH:15][N:14]([S:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)(=[O:19])=[O:18])[C:11]2=[N:12][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].C([N-]C(C)C)(C)C.[Li+].C([Li])CCC.CCCCCC.C(NC(C)C)(C)C.[O:53]1[CH2:58][CH2:57][CH:56]([CH2:59][CH:60]=[O:61])[CH2:55][CH2:54]1>O1CCCC1>[C:1]([O:5][C:6](=[O:26])[NH:7][C:8]1[CH:9]=[C:10]2[CH:16]=[C:15]([CH:60]([OH:61])[CH2:59][CH:56]3[CH2:57][CH2:58][O:53][CH2:54][CH2:55]3)[N:14]([S:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)(=[O:19])=[O:18])[C:11]2=[N:12][CH:13]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 6

HCID 7912DiisopropylamineHCID 8058HexaneHCID 2724682Lithium diisopropylamideHCID 177509432-(Oxan-4-yl)acetaldehydeHCID 67229343tert-butyl (1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)carbamateHCID 178418339Butyllithium

Product 1

HCID 67229027{1-benzenesulfonyl-2-[1-hydroxy-2-(tetrahydro-pyran-4-yl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-carbamic acid tert-butyl esterYield 33%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a suspension of (1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-carbamic acid tert-butyl ester (prepared as in Example 107, 3.4 g, 9.1 mmol) in dry tetrahydrofuran (120 mL) at −78° C. was added freshly prepared lithium diisopropylamide [prepared by adding 1.6 M n-butyllithium in n-hexane (17.1 mL, 27.3 mmol) to a 0° C. solution of diisopropylamine (2.76 g, 27.3 mmol) in dry tetrahydrofuran (20 mL)] dropwise. The mixture was stirred at −78° C. for 5 min and then treated with (tetrahydro-pyran-4-yl)-acetaldehyde (2.91 g, 22.75 mmol) dropwise. The resulting mixture was stirred at −78° C. for 1 h and quenched with brine. The mixture was extracted with ethyl acetate (2×100 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by flash column chromatography (QingDao silica gel, 200-300 mesh, 75% ethyl acetate/hexanes) afforded {1-benzenesulfonyl-2-[1-hydroxy-2-(tetrahydro-pyran-4-yl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-carbamic acid tert-butyl ester (1.5 g, 33%) as a white solid: LC/MS m/e calcd for C25H31N3O6S [M+H]+ 502.61, observed 502.2.

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 (2×100 mL)
  5. washwashed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customPurification by flash column chromatography (QingDao silica gel, 200-300 mesh, 75% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-6a2d7eb010b24b7385d8026e22baa86a
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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