Diisopropylamine → HCID 67229482, compound

HRID 1515608Notes

Reaction equation

HRID 1515608 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([CH:19]4[CH2:23][O:22][C:21]([CH3:25])([CH3:24])[O:20]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:30]([CH3:32])[CH3:31])(C)C.[Li+].C([Li])C[CH2:36][CH3:37].CCCCCC.C(NC(C)C)(C)C.[CH:52]1([CH:57]=[O:58])CCCC1>O1CCCC1>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([CH:19]4[CH2:23][O:22][C:21]([CH3:25])([CH3:24])[O:20]4)[CH:18]=[C:13]3[CH:12]=[C:11]2[CH:57]([OH:58])[CH2:52][CH:31]2[CH2:30][CH2:32][CH2:37][CH2:36]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 67228394HCID 67228394, compoundHCID 178418339Butyllithium

Product 1

HCID 67229482HCID 67229482, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of 1-benzenesulfonyl-5-(2,2-dimethyl-[1,3]dioxolan-4-yl)-1H-pyrrolo[2,3-b]pyridine (2 g, 5.59 mmol) in dry tetrahydrofuran (30 mL) at −78° C. was added freshly prepared lithium diisopropylamide [prepared by adding 1.6 M n-butyllithium in n-hexane (5.24 mL, 8.39 mmol) to a 0° C. solution of diisopropylamine (1.3 mL, 9.2 mmol) in dry tetrahydrofuran (15 mL)] dropwise. The mixture was stirred at −78° C. for 15 min and then a solution of cyclopentanecarbaldehyde (940 mg, 8.38 mmol) was added dropwise. The mixture was stirred at −78° C. for 1 h then quenched with brine. The mixture was extracted with ethyl acetate, 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-(2,2-dimethyl-[1,3]dioxolan-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-2-cyclopentyl-ethanol (1.7 g, 66%) as a white solid: LC/MS m/e calcd for C25H31N2SO5 [M+H]+ 471.59, observed 471.3; 1H NMR (400 MHz, CDCl3) δ ppm 1.25 (m, 2H), 1.48-1.75 (m, 4H), 1.49 (s, 3H), 1.56 (s, 3H), 1.80-2.17 (m, 5H, H), 3.30 (br. s., 1H), 3.71 (dd, J=7.6 Hz, 8.3 Hz, 1H), 4.33 (dd, J=6.3 Hz, 8.3 Hz, 1H), 5.14 (dd, J=6.3 Hz, 7.6 Hz, 1H), 5.36 (br, 1H), 6.63 (s, 1H), 7.47 (m, 2H), 7.57 (m, 1H), 7.81 (d, J=2.0 Hz, 1H), 8.15 (d, J=8.2 Hz, 2H), 8.37 (d, J=2.0 Hz, 1H).

Workup

  1. customprepared
  2. stirringThe mixture was stirred at −78° C. for 1 h
  3. customthen quenched with brine
  4. extractionThe mixture was extracted with ethyl acetate
  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-f035ad8f8bf845e6a8546778f6eeea70
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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