Diethyl Ether → 1-Pyrrolo[2,3-b]pyridin-1-yl-cyclopentanecarbonitrile

HRID 2169424Notes

Reaction equation

HRID 2169424 reaction equation
[H-].[Na+].[N:3]1([CH2:12][C:13]#[N:14])[C:7]2=[N:8][CH:9]=[CH:10][CH:11]=[C:6]2[CH:5]=[CH:4]1.Br[CH2:16][CH2:17][CH2:18][CH2:19]Br.CCOCC>CS(C)=O.CCCCCC.C(OCC)(=O)C>[N:3]1([C:12]2([C:13]#[N:14])[CH2:19][CH2:18][CH2:17][CH2:16]2)[C:7]2=[N:8][CH:9]=[CH:10][CH:11]=[C:6]2[CH:5]=[CH:4]1

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 80561,4-DibromobutaneHCID 24758Sodium hydrideHCID 190091892-{1H-pyrrolo[2,3-b]pyridin-1-yl}acetonitrile

Product 1

HCID 152225521-Pyrrolo[2,3-b]pyridin-1-yl-cyclopentanecarbonitrileYield 87%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of sodium hydride (60%) (8.6 g, 215.79 mmol) in dimethyl sulfoxide (90 mL) was added dropwise a mixture of pyrrolo[2,3-b]pyridin-1-yl-acetonitrile (392) (15.4 g, 98.09 mmol) and 1,4-dibromo-butane (31.7 g, 147.13 mmol) dissolved in dimethyl sulfoxide: ether (180 mL, 1:1) at 0° C. and the reaction mixture was stirred for 30 min at same temperature, then stirred at room temperature for 24 h. (TLC, 40% ethyl acetate in hexane, Rf=0.6). After completion of the reaction, the reaction mixture was quenched with 1N HCl (100 mL). Water (100 mL) was added and the mixture was extracted with ethyl acetate (3×100 mL). The separated organic part was washed with water (3×100 mL) and brine (2×100 mL) and dried and concentrated to get a crude product which was purified by Combi-Flash column (eluted at 10-20% ethyl acetate in hexane) to afford 1-pyrrolo[2,3-b]pyridin-1-yl-cyclopentanecarbonitrile (393) (18 g, 87%) as a light yellow crystalline solid.

Workup

  1. additionwas added dropwise
  2. customAfter completion of the reaction
  3. customthe reaction mixture was quenched with 1N HCl (100 mL)
  4. additionWater (100 mL) was added
  5. extractionthe mixture was extracted with ethyl acetate (3×100 mL)
  6. washThe separated organic part was washed with water (3×100 mL) and brine (2×100 mL)
  7. customdried
  8. concentrationconcentrated
  9. customto get a crude product which
  10. customwas purified by Combi-Flash column (eluted at 10-20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-a57c4ea4c97b4d678c251c116d43c5d3
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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