Diisopropylamine → HCID 67229243, compound

HRID 1515622Notes

Reaction equation

HRID 1515622 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([CH2:19][CH:20]4[CH2:24][O:23][C:22]([CH3:26])([CH3:25])[O:21]4)[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:31]([CH3:33])[CH3:32])(C)C.[Li+].C([Li])C[CH2:37][CH3:38].CCCCCC.C(NC(C)C)(C)C.[CH:53]1([CH:58]=[O:59])CCCC1>O1CCCC1>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([CH2:19][CH:20]4[CH2:24][O:23][C:22]([CH3:26])([CH3:25])[O:21]4)[CH:18]=[C:13]3[CH:12]=[C:11]2[CH:58]([OH:59])[CH2:53][CH:32]2[CH2:31][CH2:33][CH2:38][CH2:37]2)(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

8

Reactant 6

HCID 7912DiisopropylamineHCID 8058HexaneHCID 70106CyclopentanecarbaldehydeHCID 2724682Lithium diisopropylamideHCID 67228705HCID 67228705, compoundHCID 178418339Butyllithium

Product 1

HCID 67229243HCID 67229243, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a suspension of 1-benzenesulfonyl-5-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrrolo[2,3-b]pyridine (3 g, 8.06 mmol) in dry tetrahydrofuran (40 mL) at −78° C. was added freshly prepared lithium diisopropylamide [prepared by adding 1.6 M n-butyllithium in n-hexane (8.1 mL, 13.0 mmol) to a 0° C. solution of diisopropylamine (2 mL, 13.8 mmol) in dry tetrahydrofuran (20 mL)] dropwise. The mixture was stirred at −78° C. for 5 min and then cyclopentanecarbaldehyde (1.35 g, 13.0 mmol) was added dropwise. The resulting mixture was stirred at −78° C. for 1 h and quenched with brine. The mixture was extracted with ethyl acetate (2×150 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, 25% ethyl acetate/hexanes) afforded 1-[1-benzenesulfonyl-5-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-2-cyclopentyl-ethanol as a light yellow solid (850 mg, 22%): LC/MS m/e calcd for C26H32N2O5S [M+H]+ 485.62, observed 485.1.

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 (2×150 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, 25% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-ae1464cb18b64f1191983496925b9f5e
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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