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

HRID 1515581Notes

Reaction equation

HRID 1515581 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](=[O:54])[CH2:50][CH:51]([CH3:53])[CH3:52]>O1CCCC1>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[CH:13]=[C:12]([CH:49]([OH:54])[CH2:50][CH:51]([CH3:53])[CH3:52])[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 115523-MethylbutanalHCID 2724682Lithium diisopropylamideHCID 42609297methyl 1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylateHCID 178418339Butyllithium

Product 1

HCID 672290341-benzenesulfonyl-2-(1-hydroxy-3-methyl-butyl)-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methyl esterYield 36.8%

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 (2.0 g, 6.33 mmol) in dry tetrahydrofuran (15 mL) at −78° C. was added freshly prepared lithium diisopropylamide [prepared by adding 1.6 M n-butyllithium in n-hexane (5.3 mL, 8.55 mmol) to a 0° C. solution of diisopropylamine (1.3 mL, 9.2 mmol) in dry tetrahydrofuran (40 mL)] dropwise. The mixture was stirred at −78° C. for 5 min and then treated with isovaleraldehyde (1.4 mL, 13.3 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-(1-hydroxy-3-methyl-butyl)-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methyl ester as a colorless oil (938 mg, 35%): LC/MS m/e calcd for C20H23N2O5S [M+H]+ 403.47, observed 403.3; 1H NMR (400 MHz, CDCl3) δ ppm 1.04 (d, J=6.4 Hz, 3H), 1.06 (d, J=6.4 Hz, 3H), 1.82 (m, 1H), 1.94-2.03 (m, 2H), 3.30 (br, 1H), 3.94 (s, 3H), 5.45 (m, 1H), 6.70 (s, 1H), 7.49 (m, 2H), 7.59 (m, 1H), 8.19 (m, 2H), 8.41 (d, J=2.0 Hz, 1H), 9.01 (d, J=2.0 Hz, 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-769b95c1d8b548069b91598bbaf0ee5d
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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