Diisopropylamine → 1-benzenesulfonyl-2-(2-cyclopentyl-1-hydroxy-ethyl)-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methyl ester

HRID 1515588Notes

Reaction equation

HRID 1515588 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[CH:13]=[CH:12][N:11]([S:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)(=[O:16])=[O:15])[C:8]2=[N:9][CH:10]=1)=[O:4].C([N-]C(C)C)(C)C.[Li+].C([Li])CCC.CCCCCC.C(NC(C)C)(C)C.[CH:49]1([CH2:54][CH:55]=[O:56])[CH2:53][CH2:52][CH2:51][CH2:50]1>O1CCCC1>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[CH:13]=[C:12]([CH:55]([OH:56])[CH2:54][CH:49]3[CH2:53][CH2:52][CH2:51][CH2:50]3)[N:11]([S:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)(=[O:16])=[O:15])[C:8]2=[N:9][CH:10]=1)=[O:4]

Participants

8

Reactant 6

HCID 7912DiisopropylamineHCID 8058HexaneHCID 2724682Lithium diisopropylamideHCID 124898662-CyclopentylacetaldehydeHCID 42609297methyl 1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylateHCID 178418339Butyllithium

Product 1

HCID 672279581-benzenesulfonyl-2-(2-cyclopentyl-1-hydroxy-ethyl)-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methyl esterYield 21%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a suspension of 1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methyl ester (prepared as in Example 1, 2.6 g, 8.3 mmol) in dry tetrahydrofuran (60 mL) at −78° C. was added freshly prepared lithium diisopropylamide [prepared by adding 1.6 M n-butyllithium in n-hexane (6.7 mL, 10.7 mmol) to a solution of diisopropylamine (1.6 mL, 11.3 mmol) in dry tetrahydrofuran (15 mL) at 0° C.] dropwise. The mixture was stirred at −78° C. for 5 min and then treated with cyclopentyl acetaldehyde (1.2 g, 10.7 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 (2×150 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by flash column chromatography (QingDao silica gel, 200-300 mesh, 15% ethyl acetate/hexanes) afforded 1-benzenesulfonyl-2-(2-cyclopentyl-1-hydroxy-ethyl)-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methyl ester as a colorless oil (730 mg, 21%): 1H NMR (400 MHz, CDCl3) δ ppm 1.26 (m, 2H), 1.53-1.68 (m, 4H), 1.73-2.16 (m, 5H, H), 3.50 (br, 1 H), 3.89 (s, 3H), 5.41 (dd, J=5.0 Hz, 8.1 Hz, 1H), 6.67 (s, 1H), 7.42 (brt, 2H), 7.53 (brt, 1H), 8.14 (br. d., 2H), 8.33 (m, 1H), 8.96 (m, 1H).

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 column chromatography (QingDao silica gel, 200-300 mesh, 15% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-84e520e4940a429083ad6d2671306ff2
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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