Sodium hydride → 1H-Pyrrolo[2,3-b]pyridine-3-acetonitrile, 1-(methylsulfonyl)-

HRID 489734Notes

Reaction equation

HRID 489734 reaction equation
C(OP([CH2:9][C:10]#[N:11])(=O)OCC)C.[H-].[Na+].[CH3:14][S:15]([N:18]1[C:22]2=[N:23][CH:24]=[CH:25][CH:26]=[C:21]2[C:20](=O)[CH2:19]1)(=[O:17])=[O:16]>O1CCCC1.O.Cl>[CH3:14][S:15]([N:18]1[C:22]2=[N:23][CH:24]=[CH:25][CH:26]=[C:21]2[C:20]([CH2:9][C:10]#[N:11])=[CH:19]1)(=[O:16])=[O:17]

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 75676Diethyl (cyanomethyl)phosphonateHCID 222629303H-Pyrrolo[2,3-b]pyridin-3-one, 1,2-dihydro-1-(methylsulfonyl)-

Product 1

HCID 222629181H-Pyrrolo[2,3-b]pyridine-3-acetonitrile, 1-(methylsulfonyl)-Yield 81.2%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Diethyl(cyanomethyl)phosphonate (0.47 ml, 3.1 mmol) was dissolved in tetrahydrofuran (5 ml) and cooled to 0° C. Sodium hydride (0.12 g, 3.1 mmol) was added portionwise and the reaction was stirred for 10 min. 1-Methanesulfonyl-1,2-dihydro-pyrrolo[2,3-b]pyridin-3-one (0.332 g, 1.57 mmoles) suspended in tetrahydrofuran (3 ml) was added dropwise, whereupon it immediately dissolved. The reaction was stirred at room temperature for 2 h. The reaction mixture was diluted with water and neutralized with 1M hydrochloric acid The aqueous solution was extracted with ethyl acetate. The organic extract was washed with brine, dried (sodium sulfate) and concentrated under reduced pressure. The crude product was chromatographed over silica gel eluting with 50% ethyl acetate in hexane to provide pure (1-methanesulfonyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-acetonitrile (0.30 g, 45%). 1H NMR (CDCl3) δ: 3.61 (3H, s), 3.81 (2H, s), 7.34 (1H, dd, J=4.8 Hz, 7.9 Hz), 8.02 (1H, dd, J=1.6 Hz, 7.9 Hz), 8.54 (1H, dd, J=1.6 Hz, 4.8 Hz).

Workup

  1. additionwas added dropwise, whereupon it
  2. dissolutionimmediately dissolved
  3. stirringThe reaction was stirred at room temperature for 2 h
  4. extractionwas extracted with ethyl acetate
  5. extractionThe organic extract
  6. washwas washed with brine
  7. dry with materialdried (sodium sulfate)
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was chromatographed over silica gel eluting with 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-80a8f1a05ee84d5bb60db16d6416280c
Source dataset
uspto-grants-2005_12
Patent number
US06979696B2

Reaction notes

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